Sequence of the putative alanine racemase operon in Staphylococcus aureus: insertional interruption of this operon reduces d-alanine substitution of lipoteichoic acid and autolysis

Kullik, I.; Jenni, R.; Berger‐Bächi, Brigitte

doi:10.1016/s0378-1119(98)00404-1

Cited by 31 publications

(26 citation statements)

References 26 publications

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“…The mazEF genes encode a TA system (17) located immediately upstream of the rsbUVW-sigB operon and have been reported to be transcriptionally linked during heat shock (19,29,43). However, the transcriptional profile of these genes outside of heat shock has not been well characterized.…”

Section: Resultsmentioning

confidence: 99%

“…Staphyloxanthin production in various strains was quantitated as described earlier (30). Spontaneous and induced autolysis assays were performed as described previously (29).…”

Section: Methodsmentioning

confidence: 99%

“…We also examined autolysis in these strains because (i) Kullik et al noted an autolysis defect in IKA54, a S. aureus 8325-4 strain with an integrated plasmid disrupting the 1.1-kb region of alr and mazE (29), and (ii) autolysis is negatively regulated by arlRS, which in turn is positively controlled by sigB (35). While rates of spontaneous autolysis were found to be unchanged in these strains (data not shown), significant differences were seen when cells were exposed to 0.05% Triton X-100, an autolysis-inducing condition (Fig.…”

Section: Vol 191 2009mentioning

confidence: 99%

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Regulation of the mazEF Toxin-Antitoxin Module in Staphylococcus aureus and Its Impact on sigB Expression

2009

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In Staphylococcus aureus, the sigB operon codes for the alternative sigma factor B and its regulators that enable the bacteria to rapidly respond to environmental stresses via redirection of transcriptional priorities. However, a full model of B regulation in S. aureus has not yet emerged. Earlier data has suggested that mazEF, a toxin-antitoxin (TA) module immediately upstream of the sigB operon, was transcribed with the sigB operon. Here we demonstrate that the promoter P mazE upstream of mazEF is essential for full B activity and that instead of utilizing autorepression typical of TA systems, sigB downregulates this promoter, providing a negative-feedback loop for sigB to repress its own transcription. We have also found that the transcriptional regulator SarA binds and activates P mazE . In addition, P mazE was shown to respond to environmental and antibiotic stresses in a way that provides an additional layer of control over sigB expression. The antibiotic response also appears to occur in two other TA systems in S. aureus, indicating a shared mechanism of regulation.The ability of the major human pathogen Staphylococcus aureus to respond to challenging biotic (e.g., the nares of healthy individuals) (27) and abiotic environments (e.g., catheters, clothing, and doorknobs) (45) has promoted its persistence and transmission within hosts. As a result, S. aureus is now endemic to many hospitals and has become the leading cause of postoperative surgical infections (46). Furthermore, these adaptive responses have contributed to the sharp increase in S. aureus skin and soft tissue infections seen in nonrisk populations in the community (26). The ability of S. aureus to survive adverse host conditions is mediated by the alternative sigma factor B , which redirects RNA polymerase to transcribe genes involved in environmental stress responses (22 Immediately upstream of the rsbUVW-sigB operon, which codes for B and its regulators, are two small genes, mazF (SA1873) and mazE (SAS0167) (see Fig. 1E), which similar to their Escherichia coli namesakes (1), encode a toxin-antitoxin (TA) system (17). TA systems are common among prokaryotes and typically consist of a labile antitoxin that binds and inactivates a more stable toxin (18). Cellular proteases (e.g., Lon and ClpP) normally degrade these antitoxins, ensuring toxin activation if antitoxin production ever becomes interrupted. Starvation and antibiotic exposure are the most well-described stimuli of TA systems, leading to hypotheses that TA systems could be used as either a form of bacterial programmed cell death or as a way to selectively shut down the bacterium's metabolism (1, 18). Other hypotheses have laid out possible roles of TA systems in stabilizing nearby sections of the chromosome, in phage resistance, or in mediating the emergence of persister cells (33).In the present study, we expand the existing model of B regulation in S. aureus to include the transcriptional contribution from P mazE . We describe how the P mazE impacts B activity and how its activati...

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Section: Resultsmentioning

confidence: 99%

“…Staphyloxanthin production in various strains was quantitated as described earlier (30). Spontaneous and induced autolysis assays were performed as described previously (29).…”

Section: Methodsmentioning

confidence: 99%

Section: Vol 191 2009mentioning

confidence: 99%

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Regulation of the mazEF Toxin-Antitoxin Module in Staphylococcus aureus and Its Impact on sigB Expression

2009

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“…For example, dlt mutations in B. subtilis resulted in enhanced autolysis and increased susceptibility to methicillin (270,271). Furthermore, the cell walls of the mutants were more negatively charged, as indicated by the increased binding of the cationic protein cytochrome c. Effects of D-Ala ester content on autolysis were also observed in a variety of other bacterial species including S. aureus (64,140,181,197), Lactococcus lactis (234), and Lactobacillus plantarum (188). Other consequences of D-Ala depletion include increased susceptibility to a variety of different antimicrobial compounds (61,132,136,137,196,197), decreased survival in neutrophils (49,137), decreased virulence (61,138), decreased epithelial cell invasion (137), and decreased biofilm formation (61).…”

Section: Teichoic Acidsmentioning

confidence: 99%

Molecular Control of Bacterial Death and Lysis

Rice

Bayles

2008

Microbiol Mol Biol Rev

320

312

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SUMMARY Although the phenomenon of bacterial cell death and lysis has been studied for over 100 years, the contribution of these important processes to bacterial physiology and development has only recently been recognized. Contemporary study of cell death and lysis in a number of different bacteria has revealed that these processes, once thought of as being passive and unregulated, are actually governed by highly complex regulatory systems. An emerging paradigm in this field suggests that, analogous to programmed cell death in eukaryotes, regulated cell death and lysis in bacteria play an important role in both developmental processes, such as competence and biofilm development, and the elimination of damaged cells, such as those irreversibly injured by environmental or antibiotic stress. Further study in this exciting field of bacterial research may provide new insight into the potential evolutionary link between control of cell death in bacteria and programmed cell death (apoptosis) in eukaryotes.

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“…Many gram-positive and gram-negative bacteria carry genes that are homologous to mazEF (14,33). It is interesting that in several gram-positive bacteria, including Staphylococcus aureus, Bacillus subtilis (33), and Bacillus anthracis, the mazEF homologues are located immediately upstream of the sigB gene (27,33). This gene encodes B , which is a general stressresponse component (26).…”

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confidence: 99%

Escherichia coli mazEF -Mediated Cell Death Is Triggered by Various Stressful Conditions

2004

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mazEF is an Escherichia coli suicide module specific for a stable toxin and a labile antitoxin. Inhibiting mazEF expression appeared to activate the module to cause cell death. Here we show that several stressful conditions, including high temperatures, DNA damage, and oxidative stress, also induce mazEF-mediated cell death. We also show that this process takes place only during logarithmic growth and requires an intact relA gene.

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Sequence of the putative alanine racemase operon in Staphylococcus aureus: insertional interruption of this operon reduces d-alanine substitution of lipoteichoic acid and autolysis

Cited by 31 publications

References 26 publications

Regulation of the mazEF Toxin-Antitoxin Module in Staphylococcus aureus and Its Impact on sigB Expression

Regulation of the mazEF Toxin-Antitoxin Module in Staphylococcus aureus and Its Impact on sigB Expression

Molecular Control of Bacterial Death and Lysis

Escherichia coli mazEF -Mediated Cell Death Is Triggered by Various Stressful Conditions

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