Ole Andreas Løchen Økstad

• Glenna, Susanne; Birkeland, Einar Elvbakken; Orr, Russell; Gilfillan, Gregor; Dalland, Marianne & Økstad, Ole Andreas Løchen [Vis alle 8 forfattere av denne artikkelen] (2026). Longitudinal analysis of the hand microbiome in response to chlorine-based antiseptic use during a military field exercise. Microbiology spectrum. 14(8). doi: 10.1128/spectrum.03771-25. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Kaupang, Åsmund; Rongved, Pål; Kildahl-Andersen, Geir; Hylland, Knut Tormodssønn & Hovland, Ragnar [Vis alle 9 forfattere av denne artikkelen] (2025). APC24-7, a covalent combination of boronic acid and chelator moieties, restores β-lactam efficiency against metallo-β-lactamase-producers. mSphere. 10(12). doi: 10.1128/msphere.00418-25. Fulltekst i vitenarkiv Vis sammendrag

  β-Lactam/β-lactamase inhibitor combinations have significantly improved treatment outcomes for infections caused by serine β-lactamase (SBL)-producing pathogens. However, the continued emergence and spread of metallo-β-lactamases (MBLs), for which no clinically approved inhibitors currently exist, poses a serious threat to the long-term effectiveness of β-lactam-based therapies. To bridge this therapeutic gap, the boronic acid transition state analog, taniborbactam (Venatorx Pharmaceuticals), was developed, targeting SBLs and widespread MBLs such as NDM-1 and VIM-2. However, taniborbactam-escape variants have been detected among various MBL enzymes, including members of the NDM and IMP families. Here, we explored whether covalently combining two complementary inhibitor structures, a boronic acid transition state analog and a dipicolyl ethylenediamine-based metal chelator, can restore β-lactam susceptibility in MBL-producing bacterial strains, including taniborbactam-escape variants. APC24-7 successfully sensitized clinical isolates of SBL- and MBL-producing Klebsiella pneumoniae and Escherichia coli to meropenem. While APC24-7 demonstrated similarities in resensitization behavior to taniborbactam against a wide range of isogenic E. coli expressing single SBLs, APC24-7 reversed NDM-9- or IMP-26-mediated meropenem resistance more efficiently. To investigate the potential role of the chelator motif in the MBL inhibition of APC24-7, susceptibility tests were conducted with an excess of exogenous Zn² + . APC24-7-mediated resensitization remained unaffected in the presence of Zn² + for strains producing NDM-1 and VIM-2. However, its ability to reverse NDM-9- and IMP-26-mediated meropenem resistance was attenuated upon Zn² + supplementation. These findings demonstrate that combining functionally complementary chemical structures, such as chelators and boronic acids, can aid in expanding the resensitization ability of existing β-lactamase inhibitors. IMPORTANCE The ability of bacteria such as Klebsiella pneumoniae and Escherichia coli to circumvent antimicrobial chemotherapy has become a global public health crisis. The high prevalence of β-lactamase enzymes capable of rendering our most prescribed antibiotics, the β-lactams (BLs) inactive, has left us with few available treatment options against infections caused by these bacteria. The use of small molecules that inhibit especially serine β-lactamases has substantially prolonged the lifetime of BL antibiotics. Yet, most clinically available inhibitors either do not possess or have limited ability to reverse resistance conferred by metallo-β-lactamase (MBL) enzymes. Combining chelator and transition state analog technology, our hybrid compound restores the effectiveness of BL antibiotics in cases of resistance conferred by both serine β-lactamases (SBLs) and MBLs. Our approach of covalently combining a chelator with an existing SBL inhibitor scaffold offers a promising solution for managing life-threatening infections and prolonging the use of clinically available BLs.

• Vevik, Kristina; Sribasgaran, Biramitha; Cai, Kun; Naemi, Ali-Oddin; Kaspersen, Håkon & Uhlig, Silvio [Vis alle 8 forfattere av denne artikkelen] (2025). TrkA of Streptococcus mitis CCUG31611 binds cyclic di-adenosine monophosphate and is required for growth in low potassium conditions. Microbiology (Reading). ISSN 1350-0872. 171(8). doi: 10.1099/mic.0.001597. Fulltekst i vitenarkiv Vis sammendrag

  Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger regulating many physiological processes in bacteria. In the oral commensal species Streptococcus mitis, c-di-AMP is involved in regulating metabolism, growth, colony morphology, chain length, biofilm formation and DNA stress tolerance. However, no c-di-AMP-regulated effector proteins have yet been characterized in S. mitis. In this study, we first show that a ΔcdaA mutant, unable to produce c-di-AMP, grows slowly under low environmental potassium conditions. Growth of the cdaA mutant was not restored by reintroducing cdaA in the original locus (KBcdaA). Whole-genome sequencing of multiple KBcdaA isolates revealed secondary mutations in a putative potassium transporter. The mutations were predicted to result in the truncation of the protein or the alteration of a conserved glycine residue essential for selective potassium uptake, disrupting protein function. A Δpde2 mutant overproducing c-di-AMP survived poorly under high environmental sodium concentrations. We then characterized the potassium transporter regulator protein TrkA. Biochemical analyses of the purified recombinant TrkA protein revealed that it specifically binds c-di-AMP with high affinity in vitro. Using deletion mutants of trkA, we demonstrate that TrkA is essential for growth under low environmental potassium conditions. Ultra-high-performance liquid chromatography coupled to tandem mass spectrometry revealed lower c-di-AMP concentration in the ΔtrkA mutant compared to the WT. This was not due to transcriptional regulation of the expression of the c-di-AMP turnover proteins CdaA, Pde1 or Pde2. C-di-AMP production is not affected by the extracellular potassium concentrations under the conditions tested. We also demonstrate a potential role of TrkA in UV stress tolerance but do not characterize the mechanism in this study.

• Glenna, Susanne; Birkeland, Einar Elvbakken; Orr, Russell; Gilfillan, Gregor; Dalland, Marianne & Økstad, Ole Andreas [Vis alle 8 forfattere av denne artikkelen] (2025). Skin bacterial community dynamics of hands and forearms before and after military field exercise. Microbiology spectrum. 13(5). doi: 10.1128/spectrum.02953-24. Fulltekst i vitenarkiv Vis sammendrag

  The human skin microbiome is crucial for health and immunity, especially under the extreme conditions military personnel face. Soldiers often encounter unique stressors and hygienic challenges that can alter their skin’s microbial composition, particularly in field environments. In this study, we aimed to investigate the impact of military field exercises on the diversity and composition of the skin bacterial microbiota using 16S rRNA sequencing. We conducted a longitudinal study of Norwegian soldiers (n = 19) participating in outdoor training operations during the NATO winter exercise Cold Response 2022. Skin swabs were taken from soldiers' hands and forearms before and after the 10-day military exercise, and following a 3-week post-exercise leave. Our results reveal hand- and forearm-specific shifts in bacterial populations associated with the exercise, likely influenced by environmental exposure, reduced hygiene, and heightened social contact. Alpha diversity increased on forearms while remaining stable on hands, which appeared more resilient to perturbations. Both sites exhibited temporal changes in composition, with soil- and water-associated bacteria enriched post-exercise; most being transient on hands but more sustained on forearms. The soldiers’ microbiomes converged during the exercise, then diverged in the post-exercise leave period, and neither skin site returned to baseline composition at follow-up. Our findings highlight the impact of collaborative outdoor activities on microbial communities and suggest that resilience and stability differ between skin sites. IMPORTANCE Optimizing soldier health and resilience is critical for maintaining military readiness and operational effectiveness. The skin, as the body’s first line of defense, is subjected to numerous challenges in military environments. Unique environmental and hygiene challenges can disrupt the skin microbiome and increase susceptibility to skin and soft tissue infections. This longitudinal research provides valuable insights into the effects of military service on the bacterial dynamics of the skin microbiome but can also inform hygiene management and disease prevention in comparable situations.

• Marienborg, Kaja; Ambur, Ole Herman; Økstad, Ole Andreas & Skaare, Dagfinn (2023). The alginate polymer OligoG alters susceptibility of biofilm-embedded non-typeable Haemophilus influenzae to ampicillin and ciprofloxacin. JAC-Antimicrobial Resistance (JAC-AMR). 5(2). doi: 10.1093/jacamr/dlad046. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Treatment of respiratory infections with non-typeable Haemophilus influenzae (NTHi) in COPD patients is complicated by biofilm formation, protecting the bacteria against the hosts’ immune response and antibiotics. We investigated the antibiofilm and antibacterial effects of the alginate polymer OligoG, alone or combined with ampicillin or ciprofloxacin, on mature NTHi biofilms. Materials and methods Two unrelated COPD strains with PBP3-mediated β-lactam resistance, with additional TEM-1 β-lactamase (Hi-022) or quinolone resistance due to altered GyrA and ParC (Hi-072) were used. Antibiofilm and antibacterial effects were assessed macroscopically, by measurement of biofilm biomass (OD), and by viable cell counts, with determination of minimum biofilm inhibitory concentration (MBIC) and the novel parameter ‘minimum concentration for 2 log10 drop in viable cells in biofilm’ (MB2LDC). Drug interactions between OligoG and antibiotics were assessed by comparing expected and observed inhibitory effects (percent inhibition of no-treatment control) of combined treatment. Results OligoG had dose-dependent biofilm disruptive abilities and a weak inhibitory effect on viable cells. Combination with OligoG (64 g/L) significantly lowered MBIC for ampicillin (both strains) and MB2LDC for ciprofloxacin (Hi-022). For Hi-022, there was significant synergism between OligoG and both antibiotics. For Hi-072, interactions were subtle, but a tendency in direction of antagonism was significant at two concentrations of ciprofloxacin. Conclusions OligoG shows promise as a potential adjuvant to antibiotics in NTHi infections, but strain-specific factors appear to affect drug interactions and may lead to antagonism. More research is needed to clarify the mechanisms of action of OligoG and interactions with antibiotics.

• Tourasse, Nicolas Jacques; Jolley, Keith A.; Kolstø, Anne-Brit & Økstad, Ole Andreas (2023). Core genome multilocus sequence typing scheme for Bacillus cereus group bacteria. Research in Microbiology. ISSN 0923-2508. 174(6). doi: 10.1016/j.resmic.2023.104050. Fulltekst i vitenarkiv Vis sammendrag

  Core genome multilocus sequence typing (cgMLST) employs a strategy where the set of orthologous genes common to all members of a group of organisms are used for phylogenetic analysis of the group members. The Bacillus cereus group consists of species with pathogenicity towards insect species as well as warm-blooded animals including humans. While B. cereus is an opportunistic pathogen linked to a range of human disease conditions, including emesis and diarrhoea, Bacillus thuringiensis is an entomopathogenic species with toxicity toward insect larvae, and therefore used as a biological pesticide worldwide. Bacillus anthracis is a classical obligate pathogen causing anthrax, an acute lethal condition in herbivores as well as humans, and which is endemic in many parts of the world. The group also includes a range of additional species, and B. cereus group bacteria have been subject to analysis with a wide variety of phylogenetic typing systems. Here we present, based on analyses of 173 complete genomes from B. cereus group species available in public databases, the identification of a set of 1568 core genes which were used to create a core genome multilocus typing scheme for the group which is implemented in the PubMLST system as an open online database freely available to the community. The new cgMLST system provides unprecedented resolution over existing phylogenetic analysis schemes covering the B. cereus group.

• Nystedt, Helene Liepelt; Grønlien, Krister Gjestvang; Rolfsnes, Rebekka Rekkedal; Winther-Larsen, Hanne Cecilie; Økstad, Ole Andreas & Tønnesen, Hanne Hjorth (2023). Neutral natural deep eutectic solvents as anti-biofilm agents. Biofilm. 5. doi: 10.1016/j.bioflm.2023.100114. Fulltekst i vitenarkiv Vis sammendrag

  Natural deep eutectic solvents (NADES) are a class of liquids with promising properties as components in pharmaceutical formulations, such as a low toxicity profile, biodegradability and versatility. Recently, their potential use as anti-biofilm agents has been proposed, due to their ability to solubilize and stabilize biological macromolecules. In the current work, the ability to break down biofilm matrix and the biofilm killing activity of three NADES of neutral pH were investigated against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027 biofilms. The tested NADES were choline chloride:xylitol (ChX), choline chloride:glycerol (ChG) and betaine:sucrose (BS). Two of the NADES (ChX and ChG) significantly reduced the number of remaining viable cells of both bacterial species in pre-formed biofilm by 4–6 orders of magnitude, while the average biofilm biomass removal for all NADES was 27–67% (S. aureus) and 34–49% (P. aeruginosa). The tested NADES also inhibited biofilm formation of both bacterial species at concentrations at or below 0.5 x the minimal inhibitory concentration (MIC), possibly in part due to observed restrictions imposed by NADES on planktonic growth. These results demonstrate the potential value of neutral NADES as anti-biofilm agents in future antimicrobial preparations.

• Lin, Yicen; Alstrup, Monica; Pang, Janet Ka Yan; Maróti, Gergely; Er-Rafik, Mériem & Tourasse, Nicolas [Vis alle 8 forfattere av denne artikkelen] (2021). Adaptation of Bacillus thuringiensis to plant colonization affects differentiation and toxicity. mSystems. 6(5). doi: 10.1128/mSystems.00864-21. Fulltekst i vitenarkiv Vis sammendrag

  The Bacillus cereus group (Bacillus cereus sensu lato) has a diverse ecology, including various species that are vertebrate or invertebrate pathogens. Few isolates from the B. cereus group have however been demonstrated to benefit plant growth. Therefore, it is crucial to explore how bacterial development and pathogenesis evolve during plant colonization. Herein, we investigated Bacillus thuringiensis (Cry−) adaptation to the colonization of Arabidopsis thaliana roots and monitored changes in cellular differentiation in experimentally evolved isolates. Isolates from two populations displayed improved iterative ecesis on roots and increased virulence against insect larvae. Molecular dissection and recreation of a causative mutation revealed the importance of a nonsense mutation in the rho transcription terminator gene. Transcriptome analysis revealed how Rho impacts various B. thuringiensis genes involved in carbohydrate metabolism and virulence. Our work suggests that evolved multicellular aggregates have a fitness advantage over single cells when colonizing plants, creating a trade-off between swimming and multicellularity in evolved lineages, in addition to unrelated alterations in pathogenicity.

• Smith, Veronika; Nilssen, Ida Kristine Bu; Hegna, Ida Kristin; Dalhus, Bjørn; Fagerlund, Annette & Økstad, Ole Andreas (2021). CdgL is a degenerate nucleotide cyclase domain protein affecting flagellin synthesis and motility in Bacillus thuringiensis. Research in Microbiology. ISSN 0923-2508. 172(4-5). doi: 10.1016/j.resmic.2021.103850. Fulltekst i vitenarkiv Vis sammendrag

  In Bacillus subtilis, motility genes are expressed in a hierarchical pattern – governed by the σD transcription factor and other proteins such as the EpsE molecular clutch and SlrA/SlrR regulator proteins. In contrast, motile species in the Bacillus cereus group seem to express their motility genes in a non-hierarchical pattern, and less is known about their regulation, also given that no orthologs to σD, EpsE, SlrA or SlrR are found in B. cereus group genomes. Here we show that deletion of cdgL (BTB_RS26690/BTB_c54300) in Bacillus thuringiensis 407 (cry-) resulted in a six-to ten-fold downregulation of the entire motility locus, and loss of flagellar structures and swimming motility. cdgL is unique to the B. cereus group and is found in all phylogenetic clusters in the population except for group I, which comprises isolates of non-motile Bacillus pseudomycoides. Analysis of RNA-Seq data revealed cdgL to be expressed in a three-gene operon with a NupC like nucleoside transporter, and a putative glycosyl transferase for which transposon-based gene inactivation was previously shown to produce a similar phenotype to cdgL deletion. Interestingly, all three proteins were predicted to be membrane-bound and may provide a concerted function in the regulation of B. cereus group motility.

• Samuelsen, Ørjan; Åstrand, Ove Alexander Høgmoen; Frøhlich, Christopher; Heikal, Adam; Skagseth, Susann & Carlsen, Trine Josefine Olsen [Vis alle 17 forfattere av denne artikkelen] (2020). ZN148 Is a Modular Synthetic Metallo-beta-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo. Antimicrobial Agents and Chemotherapy. ISSN 0066-4804. 64(6). doi: 10.1128/AAC.02415-19. Fulltekst i vitenarkiv Vis sammendrag

  Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and <i>in vitro</i> clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical <i>Enterobacterales</i> strains (<i>n</i> = 234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing <i>Klebsiella pneumoniae</i> in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM, and no acute toxicity was observed in an <i>in vivo</i> mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ∼30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modeling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor that is capable of operating in a functional space not presently filled by any clinically approved compound.

• Smith, Veronika; Josefsen, Malin; Lindbäck, Toril; Hegna, Ida Kristin; Finke, Sarah & Tourasse, Nicolas Jacques [Vis alle 9 forfattere av denne artikkelen] (2020). MogR is a ubiquitous transcriptional repressor affecting motility, biofilm formation and virulence in Bacillus thuringiensis. Frontiers in Microbiology. 11. doi: 10.3389/fmicb.2020.610650. Fulltekst i vitenarkiv Vis sammendrag

  Flagellar motility is considered an important virulence factor in different pathogenic bacteria. In Listeria monocytogenes the transcriptional repressor MogR regulates motility in a temperature-dependent manner, directly repressing flagellar- and chemotaxis genes. The only other bacteria known to carry a mogR homolog are members of the Bacillus cereus group, which includes motile species such as B. cereus and Bacillus thuringiensis as well as the non-motile species Bacillus anthracis, Bacillus mycoides and Bacillus pseudomycoides. Furthermore, the main motility locus in B. cereus group bacteria, carrying the genes for flagellar synthesis, appears to be more closely related to L. monocytogenes than to Bacillus subtilis, which belongs to a separate phylogenetic group of Bacilli and does not carry a mogR ortholog. Here, we show that in B. thuringiensis, MogR overexpression results in non-motile cells devoid of flagella. Global gene expression profiling showed that 110 genes were differentially regulated by MogR overexpression, including flagellar motility genes, but also genes associated with virulence, stress response and biofilm lifestyle. Accordingly, phenotypic assays showed that MogR also affects cytotoxicity and biofilm formation in B. thuringiensis. Overexpression of a MogR variant mutated in two amino acids within the putative DNA binding domain restored phenotypes to those of an empty vector control. In accordance, introduction of these mutations resulted in complete loss in MogR binding to its candidate flagellar locus target site in vitro. In contrast to L. monocytogenes, MogR appears to be regulated in a growth-phase dependent and temperature-independent manner in B. thuringiensis 407. Interestingly, mogR was found to be conserved also in non-motile B. cereus group species such as B. mycoides and B. pseudomycoides, which both carry major gene deletions in the flagellar motility locus and where in B. pseudomycoides mogR is the only gene retained. Furthermore, mogR is expressed in non-motile B. anthracis. Altogether this provides indications of an expanded set of functions for MogR in B. cereus group species, beyond motility regulation. In conclusion, MogR constitutes a novel B. thuringiensis pleiotropic transcriptional regulator, acting as a repressor of motility genes, and affecting the expression of a variety of additional genes involved in biofilm formation and virulence.

• Attieh, Zaynoun; Mouawad, Carine; Rejasse, Agnès; Jehanno, Isabelle; Perchat, Stéphane & Hegna, Ida Kristin [Vis alle 10 forfattere av denne artikkelen] (2020). The fliK Gene Is Required for the Resistance of Bacillus thuringiensis to Antimicrobial Peptides and Virulence in Drosophila melanogaster. Frontiers in Microbiology. 11. doi: 10.3389/fmicb.2020.611220. Fulltekst i vitenarkiv
• Candela, Thomas; Fagerlund, Annette; Buisson, Christophe; Gilois, Nathalie; Kolstø, Anne-Brit & Økstad, Ole Andreas [Vis alle 10 forfattere av denne artikkelen] (2019). CalY is a major virulence factor and a biofilm matrix protein. Molecular Microbiology. ISSN 0950-382X. 111(6), s. 1416–1429. doi: 10.1111/mmi.14184. Fulltekst i vitenarkiv Vis sammendrag

  The extracellular biofilm matrix often contains a network of amyloid fibers which, in the human opportunistic pathogen Bacillus cereus, includes the two homologous proteins TasA and CalY. We show here, in the closely related entomopathogenic species B. thuringiensis, that CalY also displays a second function. In the early stationary phase of planktonic cultures, CalY was located at the bacterial cell‐surface, as shown by immunodetection. Deletion of calY revealed that this protein plays a major role in adhesion to HeLa epithelial cells, to the insect Galleria mellonella haemocytes, and in the bacterial virulence against larvae of this insect, suggesting that CalY is a cell‐surface adhesin. In mid‐stationary phase and in biofilms, the location of CalY shifted from the cell surface to the extracellular medium, where it was found as fibers. The transcription study and the deletion of sipW suggested that CalY change of location is due to a delayed activity of the SipW signal peptidase. Using purified CalY, we found that the protein polymerization occurred only in the presence of cell‐surface components. CalY is therefore a bifunctional protein, which switches from a cell‐surface adhesin activity in early stationary phase, to the production of fibers in mid‐stationary phase and in biofilms.

• Finke, Sarah; Fagerlund, Annette; Smith, Veronika; Krogstad, Veronica; Zhang, Mimmi Jingxi & Saragliadis, Athanasios [Vis alle 9 forfattere av denne artikkelen] (2019). Bacillus thuringiensis CbpA is a collagen binding cell surface protein under c-di-GMP control. The Cell Surface. 5, s. 1–12. doi: 10.1016/j.tcsw.2019.100032. Fulltekst i vitenarkiv Vis sammendrag

  Cyclic diguanylate (c-di-GMP) signalling affects several cellular processes in Bacillus cereus group bacteria including biofilm formation and motility, and CdgF was previously identified as a diguanylate cyclase promoting biofilm formation in B. thuringiensis. C-di-GMP can exert its function as a second messenger via riboswitch binding, and a functional c-di-GMP-responsive riboswitch has been found upstream of cbpA in various B. cereus group strains. Protein signature recognition predicted CbpA to be a cell wall-anchored surface protein with a fibrinogen or collagen binding domain. The aim of this study was to identify the binding ligand of CbpA and the function of CbpA in cellular processes that are part of the B. cereus group c-di-GMP regulatory network. By global gene expression profiling cbpA was found to be down-regulated in a cdgF deletion mutant, and cbpA exhibited maximum expression in early exponential growth. Contrary to the wild type, a ΔcbpA deletion mutant showed no binding to collagen in a cell adhesion assay, while a CbpA overexpression strain exhibited slightly increased collagen binding compared to the control. For both fibrinogen and fibronectin there was however no change in binding activity compared to controls, and CbpA did not appear to contribute to binding to abiotic surfaces (polystyrene, glass, steel). Also, the CbpA overexpression strain appeared to be less motile and showed a decrease in biofilm formation compared to the control. This study provides the first experimental proof that the binding ligand of the c-di-GMP regulated adhesin CbpA is collagen.

• Ikram, Samman; Heikal, Adam; Finke, Sarah; Hofgaard, Antje; Rehman, Yasir & Sabri, Anjum Nasim [Vis alle 7 forfattere av denne artikkelen] (2019). Bacillus cereus biofilm formation on central venous catheters of hospitalised cardiac patients. Biofouling (Print). ISSN 0892-7014. 35(2), s. 204–216. doi: 10.1080/08927014.2019.1586889. Fulltekst i vitenarkiv Vis sammendrag

  Formation of bacterial biofilms is a risk with many in situ medical devices. Biofilm-forming Bacillus species are associated with potentially life-threatening catheter-related blood stream infections in immunocompromised patients. Here, bacteria were isolated from biofilm-like structures within the lumen of central venous catheters (CVCs) from two patients admitted to cardiac hospital wards. Isolates belonged to the Bacillus cereus group, exhibited strong biofilm formation propensity, and mapped phylogenetically close to the B. cereus emetic cluster. Together, whole genome sequencing and quantitative PCR confirmed that the isolates constituted the same strain and possessed a range of genes important for and up-regulated during biofilm formation. Antimicrobial susceptibility testing demonstrated resistance to trimethoprim-sulphamethoxazole, clindamycin, penicillin and ampicillin. Inspection of the genome revealed several chromosomal beta-lactamase genes and a sulphonamide resistant variant of folP. This study clearly shows that B. cereus persisting in hospital ward environments may constitute a risk factor from repeated contamination of CVCs.

• Carlson, Colin; Getz, Wayne M.; Kausrud, Kyrre Linné; Cizauskas, Carrie A.; Blackburn, Jason K. & Carrillo, Fausto A Bustos [Vis alle 14 forfattere av denne artikkelen] (2018). Spores and soil from six sides: interdisciplinarity and the environmental biology of anthrax (Bacillus anthracis). Biological Reviews. ISSN 1464-7931. 93(4), s. 1813–1831. doi: 10.1111/brv.12420. Fulltekst i vitenarkiv
• Taiaroa, George; Samuelsen, Ørjan; Kristensen, Tom; Økstad, Ole Andreas & Heikal, Adam (2018). Complete Genome Sequence of Pseudomonas aeruginosa K34-7, a Carbapenem-Resistant Isolate of the High-Risk Sequence Type 233. Microbiology Resource Announcements (MRA). 7(4), s. 1–2. doi: 10.1128/MRA.00886-18. Fulltekst i vitenarkiv Vis sammendrag

  Carbapenem-resistant Pseudomonas aeruginosa is defined as a “critical” priority pathogen for the development of new antibiotics. Here we report the complete genome sequence of an extensively drug-resistant, Verona integron-encoded metallo-β-lactamase-expressing isolate belonging to the high-risk sequence type 233.

• Schnaars, Christian; kildahl-Andersen, Geir; Prandina, Anthony; Popal, Roya; Radix, Sylvie & Borgne, Marc Le [Vis alle 16 forfattere av denne artikkelen] (2018). Synthesis and preclinical evaluation of TPA-based zinc chelators as metallo-β-lactamase inhibitors. ACS Infectious Diseases. 4(9), s. 1407–1422. doi: 10.1021/acsinfecdis.8b00137. Fulltekst i vitenarkiv
• Heikal, Adam; Samuelsen, Ørjan; Kristensen, Tom & Økstad, Ole Andreas Løchen (2017). Complete genome sequence of a multidrug-resistant, blaNDM-1-expressing Klebsiella pneumoniae K66-45 clinical isolate from Norway. Microbiology Resource Announcements (MRA). 5:e00601(27), s. 1–2. doi: 10.1128/genomeA.00601-17. Fulltekst i vitenarkiv
• Hassan, Karl A.; Fagerlund, Annette; Elbourne, Liam D.H.; Vörös, Aniko; Kroeger, Jasmin Kaori & Simm, Roger [Vis alle 12 forfattere av denne artikkelen] (2017). The putative drug efflux systems of the Bacillus cereus group. PLOS ONE. 12(5), s. 1–25. doi: 10.1371/journal.pone.0176188. Fulltekst i vitenarkiv Vis sammendrag

  The Bacillus cereus group of bacteria includes seven closely related species, three of which, B. anthracis, B. cereus and B. thuringiensis, are pathogens of humans, animals and/ or insects. Preliminary investigations into the transport capabilities of different bacterial lineages suggested that genes encoding putative efflux systems were unusually abundant in the B. cereus group compared to other bacteria. To explore the drug efflux potential of the B. cereus group all putative efflux systems were identified in the genomes of prototypical strains of B. cereus, B. anthracis and B. thuringiensis using our Transporter Automated Annotation Pipeline. More than 90 putative drug efflux systems were found within each of these strains, accounting for up to 2.7% of their protein coding potential. Comparative analyses demonstrated that the efflux systems are highly conserved between these species; 70± 80% of the putative efflux pumps were shared between all three strains studied. Furthermore, 82% of the putative efflux system proteins encoded by the prototypical B. cereus strain ATCC 14579 (type strain) were found to be conserved in at least 80% of 169 B. cereus group strains that have high quality genome sequences available. However, only a handful of these efflux pumps have been functionally characterized. Deletion of individual efflux pump genes from B. cereus typically had little impact to drug resistance phenotypes or the general fitness of the strains, possibly because of the large numbers of alternative efflux systems that may have overlapping substrate specificities. Therefore, to gain insight into the possible transport functions of efflux systems in B. cereus, we undertook large-scale qRTPCR analyses of efflux pump gene expression following drug shocks and other stress treatments. Clustering of gene expression changes identified several groups of similarly regulated systems that may have overlapping drug resistance functions. In this article we review current knowledge of the small molecule efflux pumps encoded by the B. cereus group and suggest the likely functions of numerous uncharacterised pumps.

• Fagerlund, Annette; Smith, Veronika; Kjendseth, Åsmund Røhr; Lindbäck, Toril; Parmer, Marthe Petrine & Andersson, K. Kristoffer [Vis alle 8 forfattere av denne artikkelen] (2016). Cyclic diguanylate regulation of Bacillus cereus group biofilm formation. Molecular Microbiology. ISSN 0950-382X. 101(3), s. 471–494. doi: 10.1111/mmi.13405. Fulltekst i vitenarkiv Vis sammendrag

  Biofilm formation can be considered a bacterial virulence mechanism. In a range of Gram-negatives, increased levels of the second messenger cyclic diguanylate (c-di-GMP) promotes biofilm formation and reduces motility. Other bacterial processes known to be regulated by c-di-GMP include cell division, differentiation and virulence. Among Gram-positive bacteria, where the function of c-di-GMP signaling is less well characterized, c-di-GMP was reported to regulate swarming motility in Bacillus subtilis while having very limited or no effect on biofilm formation. In contrast, we show that in the Bacillus cereus group c-di-GMP signaling is linked to biofilm formation, and to several other phenotypes important to the lifestyle of these bacteria. The Bacillus thuringiensis 407 genome encodes eleven predicted proteins containing domains (GGDEF/EAL) related to c-di-GMP synthesis or breakdown, ten of which are conserved through the majority of clades of the B. cereus group, including Bacillus anthracis. Several of the genes were shown to affect biofilm formation, motility, enterotoxin synthesis and/or sporulation. Among these, cdgF appeared to encode a master diguanylate cyclase essential for biofilm formation in an oxygenated environment. Only two cdg genes (cdgA, cdgJ) had orthologs in B. subtilis, highlighting differences in c-di-GMP signalling between B. subtilis and B. cereus group bacteria.

• Vörös, Aniko; Simm, Roger; Slamti, Leyla; McKay, Matthew J.; Hegna, Ida Kristin & Nielsen-Leroux, Christina [Vis alle 12 forfattere av denne artikkelen] (2014). SecDF as part of the sec-translocase facilitates efficient secretion of Bacillus cereus toxins and cell wall-associated proteins. PLOS ONE. 9:e0103326(8). doi: 10.1371/journal.pone.0103326. Fulltekst i vitenarkiv
• Fagerlund, Annette; Dubois, Thomas; Økstad, Ole Andreas Løchen; Verplaetse, Emilie; Gilois, Nathalie & Bennaceur, Imene [Vis alle 12 forfattere av denne artikkelen] (2014). SinR controls enterotoxin expression in Bacillus thuringiensis biofilms. PLOS ONE. 9(1). doi: 10.1371/journal.pone.0087532. Fulltekst i vitenarkiv
• Bräunlich, Paula Marie; Økstad, Ole Andreas Løchen; Slimestad, Rune; Wangensteen, Helle; Malterud, Karl Egil & Barsett, Hilde (2013). Effects of Aronia melanocarpa constituents on biofilm formation of Escherichia coli and Bacillus cereus. Molecules. ISSN 1431-5157. 18(12), s. 14989–14999. doi: 10.3390/molecules181214989. Fulltekst i vitenarkiv
• Backe, Paul Hoff; Simm, Roger; Lærdahl, Jon Kristen; Dalhus, Bjørn; Fagerlund, Annette & Økstad, Ole Andreas Løchen [Vis alle 10 forfattere av denne artikkelen] (2013). A new family of proteins related to the HEAT-like repeat DNA glycosylases with affinity for branched DNA structures. Journal of Structural Biology. ISSN 1047-8477. 183(1), s. 66–75. doi: 10.1016/j.jsb.2013.04.007. Fulltekst i vitenarkiv Vis sammendrag

  The recently discovered HEAT-like repeat (HLR) DNA glycosylase superfamily is widely distributed in all domains of life. The present bioinformatics and phylogenetic analysis shows that HLR DNA glycosylase superfamily members in the genus Bacillus form three subfamilies: AlkC, AlkD and AlkF/AlkG. The crystal structure of AlkF shows structural similarity with the DNA glycosylases AlkC and AlkD, however neither AlkF nor AlkG display any DNA glycosylase activity. Instead, both proteins have affinity to branched DNA structures such as three-way and Holliday junctions. A unique ß-hairpin in the AlkF/AlkG subfamily is most likely inserted into the DNA major groove, and could be a structural determinant regulating DNA substrate affinity. We conclude that AlkF and AlkG represent a new family of HLR proteins with affinity for branched DNA structures.

• Vik, Unni; Logares, Ramiro; Blaalid, Rakel; Halvorsen, Rune; Carlsen, Tor & Bakke, Ingrid [Vis alle 9 forfattere av denne artikkelen] (2013). Different bacterial communities in ectomycorrhizae and surrounding soil. Scientific Reports. 3(347). doi: 10.1038/srep03471. Fulltekst i vitenarkiv Vis sammendrag

  Several eukaryotic symbioses have shown to host a rich diversity of prokaryotes that interact with their hosts. Here, we study bacterial communities associated with ectomycorrhizal root systems of Bistorta vivipara compared to bacterial communities in bulk soil using pyrosequencing of 16S rRNA amplicons. A high richness of Operational Taxonomic Units (OTUs) was found in plant roots (3,571 OTUs) and surrounding soil (3,476 OTUs). The community composition differed markedly between these two environments. Actinobacteria, Armatimonadetes, Chloroflexi and OTUs unclassified at phylum level were significantly more abundant in plant roots than in soil. A large proportion of the OTUs, especially those in plant roots, presented low similarity to Sanger 16S rRNA reference sequences, suggesting novel bacterial diversity in ectomycorrhizae. Furthermore, the bacterial communities of the plant roots were spatially structured up to a distance of 60 cm, which may be explained by bacteria using fungal hyphae as a transport vector. The analyzed ectomycorrhizae presents a distinct microbiome, which likely influence the functioning of the plant-fungus symbiosis.

• Kristoffersen, Simen Martens; Haase, Chad; Weil, M. Ryan; Passalacqua, Karla D.; Niazi, Fahim & Hutchison, Stephen [Vis alle 11 forfattere av denne artikkelen] (2012). Global mRNA decay analysis at single nucleotide resolution reveals segmental and positional degradation patterns in a Gram-positive bacterium. Genome Biology. ISSN 1465-6906. 13(4). doi: 10.1186/gb-2012-13-4-r30. Fulltekst i vitenarkiv Vis sammendrag

  Background Recent years have shown a marked increase in the use of next-generation sequencing technologies for quantification of gene expression (RNA sequencing, RNA-Seq). The expression level of a gene is a function of both its rate of transcription and RNA decay, and the influence of mRNA decay rates on gene expression in genome-wide studies of Gram-positive bacteria is under-investigated. Results In this work, we employed RNA-Seq in a genome-wide determination of mRNA half-lives in the Gram-positive bacterium Bacillus cereus. By utilizing a newly developed normalization protocol, RNA-Seq was used successfully to determine global mRNA decay rates at the single nucleotide level. The analysis revealed positional degradation patterns, with mRNAs being degraded from both ends of the molecule, indicating that both 5' to 3' and 3' to 5' directions of RNA decay are present in B. cereus. Other operons showed segmental degradation patterns where specific ORFs within polycistrons were degraded at variable rates, underlining the importance of RNA processing in gene regulation. We determined the half-lives for more than 2,700 ORFs in B. cereus ATCC 10987, ranging from less than one minute to more than fifteen minutes, and showed that mRNA decay rate correlates globally with mRNA expression level, GC content, and functional class of the ORF. Conclusions To our knowledge, this study presents the first global analysis of mRNA decay in a bacterium at single nucleotide resolution. We provide a proof of principle for using RNA-Seq in bacterial mRNA decay analysis, revealing RNA processing patterns at the single nucleotide level.

• Papazisi, Leka; Rasko, David A.; Ratnayake, Shashikala; Bock, Geoff R.; Remortel, Brian G. & Appalla, Lakshimi [Vis alle 19 forfattere av denne artikkelen] (2011). Investigating the genome diversity of B. cereus and evolutionary aspects of B. anthracis emergence. Genomics. ISSN 0888-7543. 98(1), s. 26–39. doi: 10.1016/j.ygeno.2011.03.008. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Tourasse, Nicolas; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2011). Interspersed DNA Repeats bcr1-bcr18 of Bacillus cereus Group Bacteria Form Three Distinct Groups with Different Evolutionary and Functional Patterns. Molecular Biology and Evolution (MBE). ISSN 0737-4038. 28(2), s. 963–983. doi: 10.1093/molbev/msq269. Fulltekst i vitenarkiv
• Reiter, Lillian; Tourasse, Nicolas; Fouet, Agnes; Loll, Raphaël; Davison, Sophie & Økstad, Ole Andreas Løchen [Vis alle 8 forfattere av denne artikkelen] (2011). Evolutionary History and Functional Characterization of Three Large Genes Involved in Sporulation in Bacillus cereus Group Bacteria. Journal of Bacteriology. ISSN 0021-9193. 193(19), s. 5420–5430. doi: 10.1128/JB.05309-11. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Helgason, Erlendur; Klevan, Leif Are; Sylvestre, Patricia; Moya, Maryse & Haustant, Michel [Vis alle 10 forfattere av denne artikkelen] (2011). Extended and global phylogenetic view of the Bacillus cereus group population by combination of MLST, AFLP, and MLEE genotyping data. Food Microbiology. ISSN 0740-0020. 28(2), s. 236–244. doi: 10.1016/j.fm.2010.06.014. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2010). HyperCAT: an extension of the SuperCAT database for global multi-scheme and multi-datatype phylogenetic analysis of the Bacillus cereus group population. Database: The Journal of Biological Databases and Curation. Fulltekst i vitenarkiv
• Kolstø, Anne-Brit; Tourasse, Nicolas & Økstad, Ole Andreas Løchen (2009). What Sets Bacillus anthracis Apart from Other Bacillus Species? Annual Review of Microbiology. ISSN 0066-4227. 63, s. 451–476. doi: 10.1146/annurev.micro.091208.073255. Fulltekst i vitenarkiv
• Stabell, Fredrik Bernhard; Jacobsen, Wolfgang Mathias; Risøen, Per Arne; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2009). ORF 2 from the Bacillus cereus linear plasmid pBClin15 encodes a DNA binding protein. Letters in Applied Microbiology. ISSN 0266-8254. 48(1), s. 51–57. doi: 10.1111/j.1472-765X.2008.02483.x. Fulltekst i vitenarkiv
• Gohar, Michel; Fægri, Karoline; Perchat, Stephane; Ravnum, Solveig; Økstad, Ole Andreas Løchen & Gominet, Myriam [Vis alle 8 forfattere av denne artikkelen] (2008). The PlcR Virulence Regulon of Bacillus cereus. PLOS ONE. 3(7), s. e2793–e2793. doi: 10.1371/journal.pone.0002793. Fulltekst i vitenarkiv
• Rasko, DA; Rosovitz, MJ; Økstad, Ole Andreas Løchen; Fouts, DE; Jiang, LX & Cer, RZ [Vis alle 9 forfattere av denne artikkelen] (2007). Complete sequence analysis of novel plasmids from emetic and periodontal Bacillus cereus isolates reveals a common evolutionary history among the B-cereus-group plasmids, including Bacillus anthracis pXO1. Journal of Bacteriology. ISSN 0021-9193. 189(1), s. 52–64. doi: 10.1128/JB.01313-06. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Stabell, Fredrik Bernhard; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2007). Exploring the evolution of the Bacillus cereus group repeat element bcr1 by comparative genome analysis of closely related strains. Microbiology (Reading). ISSN 1350-0872. 153, s. 3894–3908. doi: 10.1099/mic.0.2007/005504-0. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Ravnum, Solveig; Tourasse, Nicolas; Økstad, Ole Andreas Løchen; Kolstø, Anne-Brit & Davies, William (2007). Low concentrations of bile salts induce stress responses and reduce motility in Bacillus cereus ATCC 14570. Journal of Bacteriology. ISSN 0021-9193. 189(14), s. 5302–5313. doi: 10.1128/JB.00239-07. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Helgason, Erlendur; Økstad, Ole Andreas Løchen; Hegna, Ida Kristin & Kolstø, Anne-Brit (2006). The Bacillus cereus group: novel aspects of population structure and genome dynamics. Journal of Applied Microbiology. ISSN 1364-5072. 101, s. 579–593. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Smith, V; Hovland, R; Rongved, Pål & Økstad, Ole Andreas (2023). Preclinical development of a novel metallo-β-lactamase inhibitor APC148. Fulltekst i vitenarkiv
• Urtubia, Areli Moe; Winther-Larsen, Hanne Cecilie & Økstad, Ole Andreas (2023). Novel principles of drug resistance in the WHO priority 1 pathogen Acinetobacter baumannii. Fulltekst i vitenarkiv
• Glenna, S; Orr, Russell John Scott; Økstad, Ole Andreas & Voie, ØA (2023). Changes in the skin microbiome in response to antiseptic use during a NATO exercise: a metagenomic approach. Fulltekst i vitenarkiv
• Økstad, Ole Andreas (2023). The dynamic trio - the good, the bad and the ugly. Fulltekst i vitenarkiv
• Økstad, Ole Andreas (2023). Reversing carbapenem resistance in Gram-negative pathogens - Preclinical development of the modular synthetic metallo-β-lactamase inhibitor APC148. Fulltekst i vitenarkiv
• Ambur, Ole Herman; Skaare, Dagfinn & Økstad, Ole Andreas Løchen (2023). Alginate polymer alters susceptibility of biofilm-embedded non-typable Haemophilus influenzae. Fulltekst i vitenarkiv
• Marienborg, Kaja; Økstad, Ole Andreas Løchen; Ambur, Ole Herman & Skaare, Dagfinn (2023). The alginate polymer OligoG alters susceptibility of biofilm-embedded non-typeable Haemophilus influenzae to ampicillin and ciprofloxacin. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Hovland, Ragnar; Kaupang, Åsmund; Frøhlich, Christopher & Huber, Sandra [Vis alle 8 forfattere av denne artikkelen] (2023). Investigating the Mechanism of Action of a Novel Dual β-Lactamase Inhibitor. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Hovland, Ragnar; Kaupang, Åsmund; Frøhlich, Christopher & Huber, Sandra [Vis alle 8 forfattere av denne artikkelen] (2023). Investigating the Mechanism of Action of a New Novel Dual β-Lactamase Inhibitor. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Klem, Bjørn; Hovland, Ragnar; Kaupang, Åsmund & Økstad, Ole Andreas Løchen [Vis alle 7 forfattere av denne artikkelen] (2022). Bacterial antimicrobial resistance mechanisms - The novel dual serine- and metallo-β-lactamase inhibitor APC247. Fulltekst i vitenarkiv
• Hovd, Rebekka Rolfsnes; Rongved, Pål; Klem, Bjørn; Hovland, Ragnar; Kildahl-Andersen, Geir & Kaupang, Åsmund [Vis alle 8 forfattere av denne artikkelen] (2022). The novel antimicrobial resistance breaker APC247 – a putative dual serine- and metallo-β-lactamase inhibitor. Fulltekst i vitenarkiv
• Linke, Dirk; Økstad, Ole Andreas; Haugen, Håvard Jostein & Winther-Larsen, Hanne Cecilie (2021). The exchange program MISC - Options for internships at the University of Oslo (with descriptions of current projects). Fulltekst i vitenarkiv
• Liskiewicz, Krystyna Anna; Sunde, Pia Titterud; Verket, Anders; Økstad, Ole Andreas & Simm, Roger (2019). C-di-GMP signaling in Treponema denticola and its role in pathogenesis of periodontal diseases. Fulltekst i vitenarkiv
• Liskiewicz, Krystyna Anna; Sunde, Pia Titterud; Verket, Anders; Økstad, Ole Andreas & Simm, Roger (2019). C-di-GMP signaling in Treponema denticola and its role in pathogenesis of periodontal diseases. Fulltekst i vitenarkiv
• Heggelund, Julie Elisabeth; Hausvik, Emil; Carvalho, Luiz; Økstad, Ole Andreas Løchen; Martinez, Aurora & Goldman, Adrian (2018). Targeting MFS transporters to switch off antibiotic resistance in tuberculosis. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen & Linke, Dirk (2018). Hvor farlig er antibiotikaresistens? Ingeniørenes Stemme. Vinter 2018, s. 37–37. Fulltekst i vitenarkiv
• Ho, Giang Thanh Thi; Braünlich, Marie; Økstad, Ole Andreas Løchen; Slimestad, Rune; Wangensteen, Helle & Malterud, Karl Egil [Vis alle 7 forfattere av denne artikkelen] (2015). Effects of Aronia melanocarpa on biofilm formation of Escherichia coli and Bacillus cereus. Fulltekst i vitenarkiv
• Ho, Giang Thanh Thi; Braünlich, Marie; Wangensteen, Helle; Malterud, Karl Egil; Økstad, Ole Andreas Løchen & Christensen, Hege Staaland [Vis alle 9 forfattere av denne artikkelen] (2014). Spennende helseeffekter av aroniabær. Fulltekst i vitenarkiv
• Røhr, Åsmund Kjendseth; Fagerlund, Annette; Økstad, Ole Andreas Løchen & Andersson, K. Kristoffer (2013). Characterization of a redox sensor involved in Bacillus cereus biofilm formation. NBS-nytt. ISSN 0801-3535. 1, s. 62–62. Fulltekst i vitenarkiv Vis sammendrag

  The facultative aerobic, opportunistic human pathogen, Bacillus cereus is known to form biofilm under certain conditions. A common mechanism for biofilm formation depends on cyclic 3’-5’-cyclic diguanylic acid (c-di-GMP) signaling. The second messenger c-di-GMP is synthesized and degraded by the protein domains GGDEF and EAL, respectively. In order to regulate the activity of such GGDEF and EAL domains, these can be coupled to various PAS domains that act as environmental sensors of e.g. redox potential or oxygen concentration. We aim to understand how sensory PAS domains regulate the enzymatic activity of GGDEF and EAL domains through inter- or intra protein mediated interactions. The protein BC0628 from B. cereus ATCC 14579 was selected as a model system because it has a PAS-GGDEF-EAL domain structure and putative sensory, diguanylate cyclase, and phosphodiesterase activities. Here we present results showing that the soluble purified enzyme appears to bind a redox active flavin cofactor in the PAS domain. Activity assays also show that both GGDEF and EAL domains are functional and that their activities are tuned by the redox state of the PAS domain flavin cofactor. Results from initial crystallization screening are positive, thus, the BC0628 appears to be good model candidate for functional PAS-GGDEF-EAL proteins and future structural studies.

• Fagerlund, Annette; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2009). Differential gene expression and gene regulation during Bacillus thuringiensis biofilm formation. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Tourasse, Nicolas; Bakka, Eirik Rødseth; Read, Timothy D.; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2009). Repeated DNA elements in the Bacillus cereus group - implications for genome dynamics and stability of messenger RNA. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Helgason, Erlendur; Klevan, Leif Are; Sylvestre, Patricia; Moya, Maryse & Haustant, Michel [Vis alle 10 forfattere av denne artikkelen] (2009). Global multi-datatype phylogenetic analysis of the Bacillus cereus group reveals new lineages and clusters. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen & Tourasse, Nicolas (2009). Genome dynamics in the Bacillus cereus group of bacteria: introns and repeats. Fulltekst i vitenarkiv
• Kolstø, Anne-Brit; Økstad, Ole Andreas Løchen; Tourasse, Nicolas; Kristoffersen, Simen Martens; Fægri, Karoline & Fagerlund, Annette (2009). Bacillus cereus group: genome plasticity for better adaptation. Fulltekst i vitenarkiv
• Kolstø, Anne-Brit; Tourasse, Nicolas; Økstad, Ole Andreas Løchen; Fægri, Karoline & Fagerlund, Annette (2009). Bacillus cereus gene regulation and pathogenomics. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen (2009). Differential gene expression and gene regulation during biofilm formation in Bacillus thuringiensis. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Økstad, Ole Andreas Løchen; Stabell, Fredrik Bernhard; Kristoffersen, Simen Martens & Kolstø, Anne-Brit (2008). Genome dynamics in Bacillus cereus − Bacillus anthracis − Bacillus thuringiensis. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Klevan, Leif Are; Tourasse, Nicolas; Kristoffersen, Simen Martens; Langørgen, Heidi K. & Stabell, Fredrik Bernhard [Vis alle 7 forfattere av denne artikkelen] (2008). Mobile chromosomal repeat elements in pathogenic bacilli − comparative genomics and transcriptional analysis. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Klevan, Leif Are; Tourasse, Nicolas; Langørgen, Heidi K.; Stabell, Fredrik Bernhard & Kolstø, Anne-Brit [Vis alle 7 forfattere av denne artikkelen] (2008). The mobile chromosomal repeat element bcr1 from the Bacillus cereus group is co−transcribed with neighboring genes and predicted to fold into a double hairpin−like structure. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Tourasse, Nicolas; Klevan, Leif Are; Bakka, Eirik Rødseth; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2008). The Mobile Chromosomal Repeat Element bcr1in Bacillus cereus Stabilizes Adjacent mRNAs. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Klevan, Leif Are; Tourasse, Nicolas; Kristoffersen, Simen Martens; Langørgen, Heidi K. & Stabell, Fredrik Bernhard [Vis alle 7 forfattere av denne artikkelen] (2008). Mobile chromosomal repeat elements in Bacillus cereus, B. thuringiensis, and B. anthracis − Comparative genomics and transcriptional analysis. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen (2008). Bacillus anthracis, B. cereus, and B. thuringiensis − pathogenic spore-forming bacteria ACTing out an identity crisis. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Kristoffersen, Simen Martens; Langørgen, Heidi K.; Stabell, Fredrik Bernhard & Kolstø, Anne-Brit [Vis alle 7 forfattere av denne artikkelen] (2008). Mobile chromosomal repeat elements in pathogenic Bacilli − comparative genomics of isolates closely related to Bacillus anthracis and co-transcription with neighbour genes. Fulltekst i vitenarkiv
• Klevan, Are; Kristoffersen, Simen Martens; Langørgen, Heidi K.; Tourasse, Nicolas; Stabell, Fredrik Bernhard & Kolstø, Anne-Brit [Vis alle 7 forfattere av denne artikkelen] (2007). THE MOBILE CHROMOSOMAL REPEAT ELEMENT BCR1 IN BACILLUS CEREUS, B. THURINGIENSIS AND B. ANTHRACIS. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Ravnum, Solveig; Tourasse, Nicolas; Økstad, Ole Andreas Løchen; Kolstø, Anne-Brit & Davies, William (2007). Low concentrations of bile salts induce stress responses and reduce motility in the Bacillus cereus type strain. Fulltekst i vitenarkiv
• Fægri, Karoline; Ravnum, Solveig; Økstad, Ole Andreas Løchen; Tourasse, Nicolas & Kolstø, Anne-Brit (2007). Bruk av mikromatriser for å studere genregulering i Bacillus cereus. Fulltekst i vitenarkiv
• Fægri, Karoline; Hegna, Ida Kristin; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2007). Comparative analysis of global gene expression in Bacillus cereus ATCC 14579 and a deletion mutant of a membrane transporter with similarity to tetracycline resistance genes. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Klevan, Are; Tourasse, Nicolas; Stabell, Fredrik Bernhard; Kristoffersen, Simen Martens & Kolstø, Anne-Brit (2007). Mobile chromosomal repeat elements unique to the Bacillus cereus group − chromosomal organization, transcription, and secondary structure. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Ravel, Jacques; Rasko, David A; Rosovitz, MJ; Tourasse, Nicolas & Kolstø, Anne-Brit (2007). Comprehensive whole genome sequence analysis of clinical Bacillus cereus isolates from different human infections. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Tourasse, Nicolas; Hegna, Ida Kristin & Kolstø, Anne-Brit (2007). Functional and comparative genomics in pathogenic Bacillus species. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2007). Mikrobiologi-konferanse i FI-regi. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. s. 10–10. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2007). Bacillus ACT 2007 - Oslo, 17-21 June 2007. NBS-nytt. ISSN 0801-3535. s. 28–30. Fulltekst i vitenarkiv
• Biørnstad, Truls Johan; Jensen, Christine; Gohar, Michel; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2007). Biofilm formation in Bacillus cereus group pathogens − screening of isolates and functional dissection of candidate genes potentially involved in the process. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Klevan, Are; Tourasse, Nicolas; Stabell, Fredrik Bernhard & Kolstø, Anne-Brit (2007). Mobile chromosomal repeat elements in Bacillus cereus, B. thuringiensis and B. anthracis. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Ravnum, Solveig; Tourasse, Nicolas; Økstad, Ole Andreas Løchen; Kolstø, Anne-Brit & Davies, William (2007). Gene transcription responses to bile salts in Bacillus cereus ATCC 14579 – in vitro modeling of GI-tract bile exposure. Fulltekst i vitenarkiv
• Biørnstad, Truls Johan; Jensen, Christine; Gohar, Michel; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2006). Screening for biofilm formation among bacteria from the Bacillus cereus group and dissection of candidate genes potentially involved in the process. Fulltekst i vitenarkiv
• Fægri, Karoline; Ravnum, Solveig; Økstad, Ole Andreas Løchen; Tourasse, Nicolas & Kolstø, Anne-Brit (2006). Comparative analysis of global gene expression in Bacillus cereus ATCC 14579 and a derivative strain following gene deletion of delta-PlcR, a transcriptional regulator of extracellular virulence. Fulltekst i vitenarkiv
• Kristoffersen, Simen Martens; Ravnum, Solveig; Økstad, Ole Andreas Løchen; Kolstø, Anne-Brit & Davies, William (2006). Transcriptome analysis of bile salt treated Bacillus cereus ATCC 14579. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Stabell, Fredrik Bernhard; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2006). An evolutionary snapshot of the repeated element bcr1 in Bacillus cereus group strains close to the Bacillus anthracis cluster − transcription analysis, RNA folding, and traces of mobility. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen (2006). Infeksjonssykdommenes retur - hva kan genomforskning på patogene bakterier fortelle oss? Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Tourasse, Nicolas; Rasko, David A; Meisal, Roger; Helgason, Erlendur & Kolstø, Anne-Brit [Vis alle 8 forfattere av denne artikkelen] (2006). Gene discovery by comparative genome hybridization (GDCGH) − investigating gene diversity in the Bacillus cereus group of bacterial pathogens. Fulltekst i vitenarkiv
• Fægri, Karoline; Ravnum, Solveig; Økstad, Ole Andreas Løchen; Tourasse, Nicolas & Kolstø, Anne-Brit (2006). Comparing wt Bacillus cereus with a transcriptional regulator mutant. Fulltekst i vitenarkiv Vis sammendrag

  PlcR is a pleiotropic transcriptional regulator found in Bacillus cereus, an opportunistic pathogen, and Bacillus thuringiensis, an insect pathogen. The PlcR regulator has been shown to positively control a wide range of virulence factors that are exported to the extracellular environment, including a multitude of degradative enzymes, hemolysins, enterotoxins, phospholipases. We have used microarrays to perform genomewide comparisons of gene expression in B. cereus ATCC 14579 (type strain) against a plcR deletion mutant to find genes that are regulated, directly or indirectly, by PlcR. In addition to confirming the results of earlier studies, we identify several new genes regulated by PlcR, including genes involved in motility, additional degradative enzymes, and prophage-related genes. Some of these genes carry an upstream regulatory PlcR-box and may thus be directly regulated. We also observe a considerable number of genes that may be subject to indirect regulation, and the mutation seems to influence central metabolic pathways involved in energy metabolism and lipid biosynthesis.

• Klevan, Are; Tourasse, Nicolas; Stabell, Fredrik Bernhard; Helgason, Erlendur; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2006). Genome dynamics in Bacillus cereus group pathogens - in silico experiments predict mobility of the bcr1 repeat element is related to RNA secondary structure stability. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Helgason, Erlendur; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2006). Novel aspects of population and genome dynamics in the Bacillus cereus group of bacterial pathogens. Fulltekst i vitenarkiv
• Tourasse, Nicolas; Helgason, Erlendur; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2006). The Bacillus cereus group: novel aspects of population structure and genome dynamics. Fulltekst i vitenarkiv
• Biørnstad, Truls Johan; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2006). Screening for biofilm formation among bacteria from the Bacillus cereus group. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Helgason, Erlendur; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2005). The repeated element bcr1: Distribution, evolution and possible mobility in the Bacillus cereus group of bacteria. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Helgason, Erlendur; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2005). Repeated element bcr1 from the Bacillus cereus group: Distribution, evolution and possible mobility in a set of strains closely related to B. anthracis. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Stabell, Fredrik Bernhard; Helgason, Erlendur; Kolstø, Anne-Brit & Økstad, Ole Andreas Løchen (2005). Exploring the phylogeny of Bacillus cereus strains close to the B. anthracis cluster through distribution and sequence analysis of the repeated element bcr1. Fulltekst i vitenarkiv
• Klevan, Leif Are; Tourasse, Nicolas; Helgason, Erlendur; Økstad, Ole Andreas Løchen & Kolstø, Anne-Brit (2005). Distribution, evolution and possible mobility of the repeated element bcr1 by examination of Bacillus cereus group strains from the B. anthracis cluster. Fulltekst i vitenarkiv
• Økstad, Ole Andreas Løchen; Tourasse, Nicolas; Stabell, Fredrik Bernhard; Sundfær, Cathrine Kleven; Klevan, Are & Risøen, Per Arne [Vis alle 8 forfattere av denne artikkelen] (2004). bcr1, a novel mobile element specific to the Bacillus cereus group? Fulltekst i vitenarkiv

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