Influence of the ABC Transporter YtrBCDEF of Bacillus subtilis on Competence, Biofilm Formation and Cell Wall Thickness

Benda, Martin; Schulz, Lisa Maria; Stülke, Jörg; Rismondo, Jeanine

doi:10.3389/fmicb.2021.587035

Cited by 12 publications

(10 citation statements)

References 57 publications

(89 reference statements)

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“…Cell wall modification is one of several mechanisms of being involved in antibiotic resistance and has been shown to play an important role in the resistance mechanism in S. aureus , C. difficile , S. pneumoniae and S. agalactiae 48 – 50 . Also, in recent studies it is suggested that transporters can have a direct or indirect influence on peptidoglycan biosynthesis or peptidoglycan remodeling as was shown recently for the ABC transporter YtrBCDEF in B. subtilis 51 .…”

Section: Introductionmentioning

confidence: 78%

New insights into the resistance mechanism for the BceAB-type transporter SaNsrFP

Gottstein

Zaschke-Kriesche

Unsleber

et al. 2022

Sci Rep

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Treatment of bacterial infections is one of the major challenges of our time due to the evolved resistance mechanisms of pathogens against antibiotics. To circumvent this problem, it is necessary to understand the mode of action of the drug and the mechanism of resistance of the pathogen. One of the most potent antibiotic targets is peptidoglycan (PGN) biosynthesis, as this is an exclusively occurring and critical feature of bacteria. Lipid II is an essential PGN precursor synthesized in the cytosol and flipped into the outer leaflet of the membrane prior to its incorporation into nascent PGN. Antimicrobial peptides (AMPs), such as nisin and colistin, targeting PGN synthesis are considered promising weapons against multidrug-resistant bacteria. However, human pathogenic bacteria that were also resistant to these compounds evolved by the expression of an ATP-binding cassette transporter of the bacitracin efflux (BceAB) type localized in the membrane. In the human pathogen Streptococcus agalactiae, the BceAB transporter SaNsrFP is known to confer resistance to the antimicrobial peptide nisin. The exact mechanism of action for SaNsrFP is poorly understood. For a detailed characterization of the resistance mechanism, we heterologously expressed SaNsrFP in Lactococcus lactis. We demonstrated that SaNsrFP conferred resistance not only to nisin but also to a structurally diverse group of antimicrobial PGN-targeting compounds such as ramoplanin, lysobactin, or bacitracin/(Zn)-bacitracin. Growth experiments revealed that SaNsrFP-producing cells exhibited normal behavior when treated with nisin and/or bacitracin, in contrast to the nonproducing cells, for which growth was significantly reduced. We further detected the accumulation of PGN precursors in the cytoplasm after treating the cells with bacitracin. This did not appear when SaNsrFP was produced. Whole-cell proteomic protein experiments verified that the presence of SaNsrFP in L. lactis resulted in higher production of several proteins associated with cell wall modification. These included, for example, the N-acetylmuramic acid-6-phosphate etherase MurQ and UDP-glucose 4-epimerase. Analysis of components of the cell wall of SaNsrFP-producing cells implied that the transporter is involved in cell wall modification. Since we used an ATP-deficient mutant of the transporter as a comparison, we can show that SaNsrFP and its inactive mutant do not show the same phenotype, albeit expressed at similar levels, which demonstrates the ATP dependency of the mediated resistance processes. Taken together, our data agree to a target protection mechanism and imply a direct involvement of SaNsrFP in resistance by shielding the membrane-localized target of these antimicrobial peptides, resulting in modification of the cell wall.

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Section: Introductionmentioning

confidence: 78%

New insights into the resistance mechanism for the BceAB-type transporter SaNsrFP

Gottstein

Zaschke-Kriesche

Unsleber

et al. 2022

Sci Rep

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“…Genes involved in these pathways have also been observed in other transcriptomic and experimental studies. IVM-An biofilm bacteria showed the highest expression of genes encoding different ABC transporters, which suggested that these bacteria might be less metabolically active compared to bacteria in aerobic biofilms 44 . This assumption was further supported by the lower expression of genes involved in ribosome organisation, indicative of a lower growth rate of IVM- An biofilm bacteria.…”

Section: Resultsmentioning

confidence: 99%

A core transcriptional response for biofilm formation by Y. pseudotuberculosis

Mahmud

Nilsson

Soni

et al. 2022

Preprint

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Previous transcriptional profiling of the enteropathogen Yersinia pseudotuberculosis during persis-tent stages of colonisation of mouse cecal lymphoid follicles indicated the possible involvement of biofilm in infection maintenance. Not much is known about the mechanisms responsible for biofilm formation by this pathogen, and most current knowledge is based on results of experiments con-ducted using the related Y. pestis pathogen that forms biofilm in the flea gut. In this study, we per-formed transcriptional profiling of Y. pseudotuberculosis in biofilms from different biofilm-inducing conditions, bile exposure, amino acid deprivation and in vivo mimicking conditions with and with-out oxygen. The comparison of differential expression of genes in biofilm versus planktonic bacteria showed a set of 54 core genes that were similarly regulated, independent of inducing condition. This set included many genes that were previously shown to be associated with biofilms, such as hutG, hsmF, hmsT and cpxP that were upregulated and other genes such as hmsP and rfaH that were downregulated. There were also novel biofilm-associated genes, including genes encoding hypo-thetical proteins. To identify the genes involved in inducing biofilm formation, the gene expression of bacteria during an early initial phase when biofilm starts to form after induction by bile or amino acid depletion was determined. Comparisons of the resulting gene expression profiles with the pro-files of non-induced bacteria incubated for the same period of time showed a set of core genes asso-ciated with early biofilm formation. This set included genes involved in quorum sensing, pili bio-genesis and genes indicative of a potential metabolic shift involving nitrogen utilisation. Genes en-coding components of sugar phosphotransferase systems were also upregulated during biofilm in-duction. Assays of biofilm formation by bacteria deleted of some of these core genes showed that strains lacking hpr and luxS, which are known to be important for functional sugar phosphotransfer-ase systems and quorum sensing, as well as glnL encoding a sensory histidine kinase were most negatively affected. Most of the deletion mutant strains tested were affected, but the effect was less severe, suggesting high levels of redundancy in the pathways involved in biofilm formation by this pathogen.

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“…While emphasizing a low Spo0A~P as a main cause of inefficient expression of the comK gene in Rho + cells, these results strongly suggest that a stable high level of Rho also impedes the expression of other gene(s) directly or indirectly involved in the development of genetic competence. There is nothing unusual about this, since many proteins that have been shown to be essential for genetic transformation act independently and downstream of ComK [80,[114][115][116]. Interestingly, many of these proteins play essential roles in the RNA metabolism [114][115][116].…”

Section: Discussionmentioning

confidence: 99%

“…There is nothing unusual about this, since many proteins that have been shown to be essential for genetic transformation act independently and downstream of ComK [80,[114][115][116]. Interestingly, many of these proteins play essential roles in the RNA metabolism [114][115][116]. As in the case of Rho, their respective roles in the development of genetic competence remain elusive [114,116].…”

Section: Discussionmentioning

confidence: 99%

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Termination factor Rho mediates transcriptional reprogramming ofBacillus subtilisstationary phase

Bidnenko

Nicolas

Guérin

et al. 2022

Preprint

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Reprogramming of gene expression during transition from exponential growth to stationary phase is crucial for bacterial survival. In the model Gram-positive bacterium Bacillus subtilis, this process is mainly governed by the activity of the global transcription regulators AbrB, CodY and Spo0A. We recently showed that the transcription termination factor Rho, known for its ubiquitous role in the inhibition of antisense transcription, is involved in Spo0A-mediated regulation of differentiation programs specific to the stationary phase in B. subtilis. To identify other aspects of the regulatory role of Rho during adaptation to starvation, we have constructed a B. subtilis strain that expresses rho at a relatively stable high level in order to circumvent its decrease occurring in the wild-type cells entering the stationary phase. We show that B. subtilis cells stably expressing Rho fail to sporulate and to develop genetic competence, which is largely, but not exclusively, due to abnormally low expression of the master regulator Spo0A. Moreover, in addition to a global decrease of antisense transcription, these cells exhibit genome-wide alterations of sense transcription. A significant part of these alterations affects genes from global regulatory networks of cellular adaptation to the stationary phase and reflects the attenuated de-repression of the AbrB and CodY regulons and the weakened stringent response. Accordingly, stabilization of Rho level reprograms stationary phase-specific physiology of B. subtilis cells, negatively affects cellular adaptation to nutrient limitations and alters cell-fate decision-making to such an extent that it blocks development of genetic competence and sporulation. Taken together, these results indicate that the activity of termination factor Rho constitutes a previously unknown layer of control over the stationary phase and post-exponential adaptive strategies in B. subtilis, from the adjustment of cellular metabolism to the activation of survival programs.

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Influence of the ABC Transporter YtrBCDEF of Bacillus subtilis on Competence, Biofilm Formation and Cell Wall Thickness

Cited by 12 publications

References 57 publications

New insights into the resistance mechanism for the BceAB-type transporter SaNsrFP

New insights into the resistance mechanism for the BceAB-type transporter SaNsrFP

A core transcriptional response for biofilm formation by Y. pseudotuberculosis

Termination factor Rho mediates transcriptional reprogramming ofBacillus subtilisstationary phase

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