Veronika Smith

• Smith, Veronika; Josefsen, Malin; Lindbäck, Toril; Hegna, Ida Kristin; Finke, Sarah; Tourasse, Nicolas Jacques; Nielsen-LeRoux, Christina; Økstad, Ole Andreas & Fagerlund, Annette (2020). MogR is a ubiquitous transcriptional repressor affecting motility, biofilm formation and virulence in Bacillus thuringiensis. Frontiers in Microbiology.  ISSN 1664-302X.  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.

• Finke, Sarah; Fagerlund, Annette; Smith, Veronika; Krogstad, Veronica; Zhang, Mimmi Jingxi; Saragliadis, Athanasios; Linke, Dirk; Nielsen-Leroux, Christina & Økstad, Ole Andreas (2019). Bacillus thuringiensis CbpA is a collagen binding cell surface protein under c-di-GMP control. The Cell Surface.  ISSN 2468-2330.  5, s 1- 12 . doi: 10.1016/j.tcsw.2019.100032 Fulltekst i vitenarkiv.
• Fagerlund, Annette; Smith, Veronika; Kjendseth, Åsmund Røhr; Lindbäck, Toril; Parmer, Marthe Petrine; Andersson, K. Kristoffer; Reubsaet, Leon & Økstad, Ole Andreas Løchen (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 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.

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