Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus subtilisσW and σM regulons

Cao, Min; Wang, Tao; Ye, Rick; Helmann, John D.

doi:10.1046/j.1365-2958.2002.03050.x

Cited by 233 publications

(282 citation statements)

References 51 publications

Supporting

Mentioning

261

Contrasting

Order By: Relevance

“…When similar experiments were performed in B. subtilis, 10 min exposure was enough to obtain the induction of 129 genes (Cao et al, 2002), suggesting that some time is required for vancomycin to cross the mycobacterial outer membrane and exert its action. Quantitative RT-PCR was used to validate the differential expression of selected genes (Supplementary Tables S2 and S3, available with the online version of this paper).…”

Section: Resultsmentioning

confidence: 93%

“…1a). A 10X-MIC of vancomycin was also used by Cao et al (2002) in B. subtilis to identify an inducible defensive response against antibiotics coordinated by alternative sigma factors. Subinhibitory conditions were determined by growing bacteria in the presence of decreasing vancomycin concentrations (twofold serial dilutions) starting from the MIC (40 mg ml 21 ) (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…This approach has been successfully used to study the global transcriptional response of Bacillus subtilis and Staphylococcus aureus in response to several inhibitors of peptidoglycan biosynthesis (Cao et al, 2002;Mascher et al, 2003;Utaida et al, 2003), and in M. tuberculosis to study the transcriptional response to the detergent SDS (Manganelli et al, 2001) and to the mycolic acid biosynthesis inhibitor isoniazid (Wilson et al, 1999). These experiments contributed to the understanding of the physiological mechanisms used by bacteria to maintain surface homeostasis and to identify several potential targets for the development of new antibacterial drugs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Global transcriptional response to vancomycin in Mycobacterium tuberculosis

et al. 2009

View full text Add to dashboard Cite

In order to gain additional understanding of the physiological mechanisms used by bacteria to maintain surface homeostasis and to identify potential targets for new antibacterial drugs, we analysed the variation of the Mycobacterium tuberculosis transcriptional profile in response to inhibitory and subinhibitory concentrations of vancomycin. Our analysis identified 153 genes differentially regulated after exposing bacteria to a concentration of the drug ten times higher than the MIC, and 141 genes differentially expressed when bacteria were growing in a concentration of the drug eightfold lower than the MIC. Hierarchical clustering analysis indicated that the response to these different conditions is different, although with some overlap. This approach allowed us to identify several genes whose products could be involved in the protection from antibiotic stress targeting the envelope and help to confer the basal level of M. tuberculosis resistance to antibacterial drugs, such as Rv2623 (UspA-like), Rv0116c, PE20-PPE31, PspA and proteins related to toxin-antitoxin systems. Moreover, we also demonstrated that the alternative sigma factor s E confers basal resistance to vancomycin, once again underlining its importance in the physiology of the mycobacterial surface stress response. INTRODUCTIONMycobacterium tuberculosis remains one of the world's most prevalent and serious pathogens. It is estimated that every year 2 million people die as a direct result of tuberculosis and that there is a reservoir of 2 billion cryptically infected people (Dye et al., 1999). Of these asymptomatic carriers, around 5 % will develop active disease at some stage in their lives and in doing so will contribute to the ongoing transmission of infection (Raviglione, 2003). The recent emergence of multidrugresistant (MDR) and extensively drug-resistant (XDR-TB) strains (Gandhi et al., 2006) has raised the importance of searching for alternative targets to develop new antimycobacterial drugs.Due to the importance of its physiological role and its difference from the eukaryotic cell surface, the bacterial cell wall is one of the best candidates in the search for new drug targets. A large number of antibacterial drugs currently in use are directed against surface components or metabolic pathways that are involved in their synthesis. For example, b-lactams, cephalosporins, glycopeptides, phosphomycin, bacitracin and cycloserine inhibit peptidoglycan biosynthesis, while polymyxin interferes with the cell-membrane structure. Moreover, compounds such as isoniazid, pyrazinamide, ethambutol and ethionamide target typical components of the mycobacterial cell surface. In spite of a good knowledge of the chemical composition of the mycobacterial surface, not much is known about its organization and physiology (Barry, 2001). The recent demonstration of the presence of an outer membrane will surely boost research in this field (Hoffmann et al., 2008;Zuber et al., 2008).One strategy to study bacterial surface physiology is to characterize the variation o...

show abstract

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Global transcriptional response to vancomycin in Mycobacterium tuberculosis

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The cell membrane is the first barrier to an increased ionic strength, and the sensing mechanism would take place in it (Poolman et al, 2002(Poolman et al, , 2004. In addition, several sigma factors required for extracytoplasmic functions (membrane and wall synthesis) have been shown to respond to stress effectors (Cao et al, 2002). In particular, Horsburgh & Moir (1999) showed that in B. subtilis, the sigM gene product is required for normal cell growth under salt stress.…”

Section: Introductionmentioning

confidence: 99%

Role of anionic phospholipids in the adaptation of Bacillus subtilis to high salinity

et al. 2006

View full text Add to dashboard Cite

The importance of the content of anionic phospholipids [cardiolipin (CL) and phosphatidylglycerol (PG)] in the osmotic adaptation and in the membrane structure of Bacillus subtilis cultures was investigated. Insertion mutations in the three putative cardiolipin synthase genes (ywiE, ywnE and ywjE) were obtained. Only the ywnE mutation resulted in a complete deficiency in cardiolipin and thus corresponds to a true clsA gene. The osmotolerance of a clsA mutant was impaired: although at NaCl concentrations lower than 1?2 M the growth curves were similar to those of its wild-type control, at 1?5 M NaCl (LBN medium) the lag period increased and the maximal optical density reached was lower. The membrane of the clsA mutant strain showed an increased PG content, at both exponential and stationary phase, but no trace of CL in either LB or LBN medium. As well as the deficiency in CL synthesis, the clsA mutant showed other differences in lipid and fatty acids content compared to the wild-type, suggesting a cross-regulation in membrane lipid pathways, crucial for the maintenance of membrane functionality and integrity. The biophysical characteristics of membranes and large unilamellar vesicles from the wild-type and clsA mutant strains were studied by Laurdan's steady-state fluorescence spectroscopy. At physiological temperature, the clsA mutant showed a decreased lateral lipid packing in the protein-free vesicles and isolated membranes compared with the wild-type strain. Interestingly, the lateral lipid packing of the membranes of both the wild-type and clsA mutant strains increased when they were grown in LBN. In a conditional IPTG-controlled pgsA mutant, unable to synthesize PG and CL in the absence of IPTG, the osmoresistance of the cultures correlated with their content of anionic phospholipids. The transcriptional activity of the clsA and pgsA genes was similar and increased twofold upon entry to stationary phase or under osmotic upshift. Overall, these results support the involvement of the anionic phospholipids in the growth of B. subtilis in media containing elevated NaCl concentrations.

show abstract

“…ECF s factors regulate the expression of target genes in response to changing physicochemical conditions in the cellular environment (Helmann, 2002). In the case of SigO and RsoA, the two-subunit s factor is expressed in the cell after exposure to certain cell-wall-acting antibiotics and acid stress conditions (Cao et al, 2002;Hachmann et al, 2009;MacLellan et al, 2009b). The SigO-RsoA regulon member gene rsiO (formerly known as yvrL) (see Fig.…”

Section: Introductionmentioning

confidence: 99%

The atypical two-subunit σ factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress

2016

View full text Add to dashboard Cite

The atypical two-subunit s factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress Extracytoplasmic function (ECF) s factors constitute a major component of the physicochemical sensory apparatus in bacteria. Most ECF s factors are co-expressed with a negative regulator called an anti-s factor that binds to its cognate s factor and sequesters it from productive association with core RNA polymerase (RNAP). Anti-s factors constitute an important element of signal transduction pathways that mediate an appropriate transcriptional response to changing environmental conditions. The Bacillus subtilis genome encodes seven canonical ECF s factors and six of these are co-expressed with experimentally verified anti-s factors. B. subtilis also expresses an ECF-like atypical two-subunit s factor composed of subunits SigO and RsoA that becomes active after exposure to certain cell-wall-acting antibiotics and to growth under acidic conditions. This work describes the identification and preliminary characterization of a protein (RsiO, formerly YvrL) that constitutes the anti-s factor cognate to SigO-RsoA. Synthesis of RsiO represses SigO-RsoA-dependent transcription initiation by binding the N-terminus of SigO under neutral (pH 7) conditions. Reconstitution of the SigO-RsoA-RsiO regulatory system into a heterologous host reveals that the imposition of acid stress (pH 5.4) abolishes the ability of RsiO to repress SigO-RsoA-dependent transcription and this correlates with loss of RsiO binding affinity for SigO. A current model for RsiO function indicates that RsiO responds, either directly or indirectly, to increased extracytoplasmic hydrogen ion concentration and becomes inactivated. This results in the release of SigO into the cytoplasm, where it productively associates with RsoA and core RNAP to initiate transcription from target promoters in the cell.

show abstract

Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus subtilisσ^W and σ^M regulons

Cited by 233 publications

References 51 publications

Global transcriptional response to vancomycin in Mycobacterium tuberculosis

Global transcriptional response to vancomycin in Mycobacterium tuberculosis

Role of anionic phospholipids in the adaptation of Bacillus subtilis to high salinity

The atypical two-subunit σ factor from Bacillus subtilis is regulated by an integral membrane protein and acid stress

Contact Info

Product

Resources

About