Thermal control of virulence factors in bacteria: A hot topic

Lam, Oliver; Wheeler, Jun X.; Tang, Christoph M.

doi:10.4161/21505594.2014.970949

Cited by 58 publications

(46 citation statements)

References 138 publications

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“…Temperature-related changes in gene expression are typically regulated at the level of transcription, via changes in DNA structure that expose RNA polymerase, activator or repressor binding sites, or activation of alternative factors or through changes in promoter or repressor protein structure or oligomeric state that influence DNA binding. Alternatively, regulation can occur at the level of translation initiation through "RNA thermometer" structures that allow the ribosome access only at the elevated temperature (31). In this study, we have provided evidence for another mechanism of thermoregulation through direct protein structural changes in the P. aeruginosa methyltransferase EftM.…”

Section: Discussionmentioning

confidence: 65%

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Pseudomonas aeruginosa EftM Is a Thermoregulated Methyltransferase

Owings

Kuiper²,

Prezioso

et al. 2016

Journal of Biological Chemistry

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Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that trimethylates elongation factor-thermo-unstable (EF-Tu) on lysine 5. Lysine 5 methylation occurs in a temperature-dependent manner and is generally only seen when P. aeruginosa is grown at temperatures close to ambient (25°C) but not at higher temperatures (37°C). We have previously identified the gene, eftM (for EF-Tu-modifying enzyme), responsible for this modification and shown its activity to be associated with increased bacterial adhesion to and invasion of respiratory epithelial cells. Bioinformatic analyses predicted EftM to be a Class I S-adenosyl-L-methionine (SAM)-dependent methyltransferase. An in vitro methyltransferase assay was employed to show that, in the presence of SAM, EftM directly trimethylates EF-Tu. A natural variant of EftM, with a glycine to arginine substitution at position 50 in the predicted SAM-binding domain, lacks both SAM binding and enzyme activity. Mass spectrometry analysis of the in vitro methyltransferase reaction products revealed that EftM exclusively methylates at lysine 5 of EF-Tu in a distributive manner. Consistent with the in vivo temperature dependence of methylation of EF-Tu, preincubation of EftM at 37°C abolished methyltransferase activity, whereas this activity was retained when EftM was preincubated at 25°C. Irreversible protein unfolding at 37°C was observed, and we propose that this instability is the molecular basis for the temperature dependence of EftM activity. Collectively, our results show that EftM is a thermolabile, SAM-dependent methyltransferase that directly trimethylates lysine 5 of EF-Tu in P. aeruginosa.Protein post-translational modification adds an additional level of complexity that can influence protein function as well as change the protein charge and tertiary structure. The protein post-translational modification landscape is vast; more than half of the natural amino acids are substrates for chemical modification, and lysine, for example, can be modified with at least 10 different post-translational modifications, including methylation (1).Although first discovered on the bacterial flagellum (2), the study of lysine methylation in prokaryotes has lagged behind that of eukaryotes. In eukaryotes, the most well studied effect of lysine methylation is within the field of epigenetics, where patterns of methylation form the "histone code," and serve as another level of DNA transcriptional control (3). In bacteria, methylated lysines have been found on flagella, specific outer membrane proteins, and the ribosome translational machinery; however, for the most part, the functional consequences of these modifications are not known (2, 4 -8).Post-translational modification of proteins involved in protein synthesis has the potential to exert a significant effect on bacterial gene expression. Lysine methylation of components of the translational machinery, including essential translation factors such as elongation factor-thermo-unstable (EF-Tu), 6 which binds to and delivers aminoacyla...

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Section: Discussionmentioning

confidence: 65%

“…Bacteria possess multiple strategies to adapt to changes in temperature: the heat shock, cold shock, and the low and the high temperature responses (31). These distinct pathways each employ DNA, RNA, or protein molecules as the effectors of the response.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa EftM Is a Thermoregulated Methyltransferase

Owings

Kuiper²,

Prezioso

et al. 2016

Journal of Biological Chemistry

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“…In addition to H-NS temperature-dependent regulation, thermosensing mechanisms can act at different levels. Indeed, temperature regulation can occur at the DNA level through Yad Fimbriae Promote E. coli Environmental Persistence 5241 modulation of DNA supercoiling, as in the case of type 1 fimbrial regulation or of DNA curvature, through mRNA secondary or tertiary structure modification such as in Listeria monocytogenes silencing of virulence genes, or directly at the protein level (Johansson et al, 2002;Kelly et al, 2006;Lam et al, 2014). While we showed that temperature transcriptional regulation of yad expression is H-NS independent, the mechanism and/or regulator beyond this regulation still needs to be identified.…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of Escherichia coliYad fimbriae reveals their potential role in environmental persistence

Larsonneur

Martín

Mallet

et al. 2016

Environmental Microbiology

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Initial adhesion of bacterial cells to surfaces or host tissues is a key step in colonisation and biofilm formation processes, and is mediated by cell surface appendages. It was previously demonstrated that Escherichia coli K-12 possesses an arsenal of silenced chaperone-usher fimbriae that were functional when constitutively expressed. Among them, production of prevalent Yad fimbriae induces adhesion to abiotic surfaces. Functional characterisation of Yad fimbriae were undertook, and YadN was identified as the most abundant and potential major pilin, and YadC as the potential tip-protein of Yad fimbriae. It was showed that Yad production participates to binding of E. coli K-12 to human eukaryotic cells (Caco-2) and inhibits macrophage phagocytosis, but also enhances E. coli K-12 binding to xylose, a major component of the plant cell wall, through its tip-lectin YadC. Consistently, it was demonstrated that Yad production provides E. coli with a competitive advantage in colonising corn seed rhizospheres. The latter phenotype is correlated with induction of Yad expression at temperatures below 37°C, and under anaerobic conditions, through a complex regulatory network. Taken together, these results suggest that Yad fimbriae are versatile adhesins that beyond potential capacities to modulate host-pathogen interactions might contribute to E. coli environmental persistence.

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“…All of the above has important consequences for infectious diseases, as the cell membrane is one of the first contact sensing changes down to 1ºC (69). They importantly control virulence factors in bacteria (70,71).…”

Section: Molecular Consequences During Fever: a Theorymentioning

confidence: 99%