Regulation of bacterial virulence gene expression by cell envelope stress responses

Flores-Kim, Josué; Darwin, Andrew J.

doi:10.4161/21505594.2014.965580

Cited by 37 publications

(35 citation statements)

References 199 publications

(294 reference statements)

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“…Therefore, the proper synthesis and maintenance of the PGN, but also a correct architecture, are essential not only for bacterial virulence but also for viability, since, for instance, defects in the structural lipoproteins (or their anchoring to PGN) usually drive the outer membrane to a loss of integrity, leading to periplasmic protein leakage, vesicle formation, blebbing, etc (25,28). As mentioned in the introduction, the PGN of Gram-positive bacterial species has classically been bestowed with great importance in terms of resistance against the action of immune weapons or certain antibiotics, but also as a key virulence factor often related to the inflammatory response elicited in the host (20)(21)(22)(29)(30)(31)(32). However, given the protection exerted by the outer membrane and the anchored lipopolysaccharide (LPS) and its thinner width, the PGN of Gram-negative species has not been given such a protagonistic role, or at least a role not as important as that of the Gram-positive PGN.…”

Section: Dealing With Cell Wall Structure: Peptidoglycan-associated Lmentioning

confidence: 99%

Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens

Juan

Torrens

Barceló

2018

Microbiol Mol Biol Rev

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The clinical and epidemiological threat of the growing antimicrobial resistance in Gram-negative pathogens, particularly for β-lactams, the most frequently used and relevant antibiotics, urges research to find new therapeutic weapons to combat the infections caused by these microorganisms. An essential previous step in the development of these therapeutic solutions is to identify their potential targets in the biology of the pathogen. This is precisely what we sought to do in this review specifically regarding the barely exploited field analyzing the interplay among the biology of the peptidoglycan and related processes, such as β-lactamase regulation and virulence. Hence, here we gather, analyze, and integrate the knowledge derived from published works that provide information on the topic, starting with those dealing with the historically neglected essential role of the Gram-negative peptidoglycan in virulence, including structural, biogenesis, remodeling, and recycling aspects, in addition to proinflammatory and other interactions with the host. We also review the complex link between intrinsic β-lactamase production and peptidoglycan metabolism, as well as the biological costs potentially associated with the expression of horizontally acquired β-lactamases. Finally, we analyze the existing evidence from multiple perspectives to provide useful clues for identifying targets enabling the future development of therapeutic options attacking the peptidoglycan-virulence interconnection as a key weak point of the Gram-negative pathogens to be used, if not to kill the bacteria, to mitigate their capacity to produce severe infections.

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Section: Dealing With Cell Wall Structure: Peptidoglycan-associated Lmentioning

confidence: 99%

Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens

Juan

Torrens

Barceló

2018

Microbiol Mol Biol Rev

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“…Given that the cell envelope is constantly exposed to the environment, adaptive responses must be maintained or cell viability will be lost (18,19). Across many bacterial species, the regulatory process surrounding the cell envelope stress response consists of extracytoplasmic function (ECF) factors and two-component systems (TCS) (20,21,22).…”

mentioning

confidence: 99%

“…Across many bacterial species, the regulatory process surrounding the cell envelope stress response consists of extracytoplasmic function (ECF) factors and two-component systems (TCS) (20,21,22). In the Firmicutes (low GϩC Gram-positive bacteria), numerous two-and three-component systems respond to envelopedamaging agents, including antimicrobial peptides and antibiotics (18,23). One such example is the LiaFSR (lipid II-interacting antibiotic response regulator and sensor) system, which was first identified in Bacillus subtilis (24).…”

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confidence: 99%

Exogenous Fatty Acids Protect Enterococcus faecalis from Daptomycin-Induced Membrane Stress Independently of the Response Regulator LiaR

Harp

Saito

Bourdon

et al. 2016

Appl Environ Microbiol

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Enterococcus faecalis is a commensal bacterium of the gastrointestinal tract that can cause nosocomial infections in immunocompromised humans. The hallmarks of this organism are its ability to survive in a variety of stressful habitats and, in particular, its ability to withstand membrane damage. One strategy used by E. faecalis to protect itself from membrane-damaging agents, including the antibiotic daptomycin, involves incorporation of exogenous fatty acids from bile or serum into the cell membrane. Additionally, the response regulator LiaR (a member of the LiaFSR [lipid II-interacting antibiotic response regulator and sensor] system associated with cell envelope stress responses) is required for the basal level of resistance E. faecalis has to daptomycin-induced membrane damage. This study aimed to determine if membrane fatty acid changes could provide protection against membrane stressors in a LiaR-deficient strain of E. faecalis. We noted that despite the loss of LiaR, the organism readily incorporated exogenous fatty acids into its membrane, and indeed growth in the presence of exogenous fatty acids increased the survival of LiaR-deficient cells when challenged with a variety of membrane stressors, including daptomycin. Combined, our results suggest that E. faecalis can utilize both LiaR-dependent and -independent mechanisms to protect itself from membrane damage. IMPORTANCEEnterococcus faecalis is responsible for a significant number of nosocomial infections. Worse, many of the antibiotics used to treat E. faecalis infection are no longer effective, as this organism has developed resistance to them. The drug daptomycin has been successfully used to treat some of these resistant strains; however, daptomycin-resistant isolates have been identified in hospitals. Many daptomycin-resistant isolates are found to harbor mutations in the genetic locus liaFSR, which is involved in membrane stress responses. Another mechanism shown to increase tolerance to daptomycin involves the incorporation of exogenous fatty acids from host fluids like serum or bile. This improved tolerance was found to be independent of liaFSR and suggests that there are additional ways to impact sensitivity to daptomycin. Thus, further studies are needed to understand how host fatty acid sources can influence antibiotic susceptibility. Enterococcus faecalis is a Gram-positive, facultative anaerobe that resides in the gastrointestinal tract of humans and many other mammalian species (1). Additionally, the organism is known to persist in the external environment for significant periods of time, demonstrating its ability to withstand a variety of changing conditions. Despite the commensal nature of E. faecalis, it is a significant contributor to nosocomial infections, including bloodstream, skin and soft tissue, and urinary tract infections, endocarditis, and meningitis in immunocompromised patients (2, 3). Eradication of E. faecalis, especially in regard to such infections, is challenging as the organism is inherently resistant to a va...

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“…49,50 It is important to note that while the electrolyte composition of 50 mM KCl was tolerated by our bacteria strains (see SI-4), it is possible that the absence of carbon source and physiological media conditions could cause a certain degree of cellular stress, possibly affecting the charge in the bacterial cell envelope. 51 However, similarly high normalized currents were also found when we used a physiological media (M9m) as the electrolyte to scan B. subtilis Dhag (SI-10, Figure S-12).…”

Section: Resultsmentioning

confidence: 57%

Scanning ion conductance microscopy reveals differences in the ionic environments of gram positive and negative bacteria

Cremin

Jones

Teahan

et al. 2020

Preprint

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This paper reports on the use of scanning ion conductance microscopy (SICM) to locally map the ionic properties and charge environment of two live bacterial strains: the gramnegative Escherichia coli and the gram-positive Bacillus subtilis. SICM results find heterogeneities across the bacterial surface, and significant differences among the grampositive and -negative bacteria. The bioelectrical environment of the B. subtilis was found to be considerably more negatively charged compared to E. coli. SICM measurements, fitted to a simplified finite element method (FEM) model, revealed surface charge values of −80 to −140 mC m−2 for the gram-negative E. coli. The gram-positive B. subtilis show a much higher conductivity around the cell wall, and surface charge values between −350 and −450 mC m−2 were found using the same simplified model. SICM was also able to detect regions of high negative charge near B. subtilis, not detected in the topographical SICM response and attributed to extracellular polymeric substance. To further explore how the B. subtilis cell wall structure can influence the SICM current response, a more comprehensive FEM model, accounting for the physical properties of the gram-positive cell wall, was developed. The new model provides a more realistic description of the cell wall and allowed investigation of the relation between its key properties and SICM currents, building foundations to further investigate and improve understanding of the gram-positive cellular microenvironment.Abstract Figure

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Regulation of bacterial virulence gene expression by cell envelope stress responses

Cited by 37 publications

References 199 publications

Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens

Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens

Exogenous Fatty Acids Protect Enterococcus faecalis from Daptomycin-Induced Membrane Stress Independently of the Response Regulator LiaR

Scanning ion conductance microscopy reveals differences in the ionic environments of gram positive and negative bacteria

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