The Biofilm Lifestyle Involves an Increase in Bacterial Membrane Saturated Fatty Acids

Dubois‐Brissonnet, Florence; Trotier, Elsa; Briandet, Romain

doi:10.3389/fmicb.2016.01673

Cited by 83 publications

(70 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…that fluidifies membranes (28,34). Bacterial growth was simultaneously determined in the presence of either C 18 or C 18:1 without daptomycin, showing that no fatty acidinduced toxicity occurred in the tested conditions (see Fig.…”

Section: Resultsmentioning

confidence: 92%

“…In this context, we reasoned that, as the bacterial membrane is the daptomycin target, an investigation of membrane composition properties would give insight on the parameters affecting bactericidal activity. In particular, slow-growing and biofilm bacteria were recently shown to exhibit more rigid membranes than those of actively growing cells, which may be one reason for bacterial recalcitrance to daptomycin (28).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impact of Bacterial Membrane Fatty Acid Composition on the Failure of Daptomycin To Kill Staphylococcus aureus

Boudjemaa

Cabriel

Dubois‐Brissonnet

et al. 2018

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Daptomycin is a last-resort membrane-targeting lipopeptide approved for the treatment of drug-resistant staphylococcal infections, such as bacteremia and implant-related infections. Although cases of resistance to this antibiotic are rare, increasing numbers of clinical,in vitro, and animal studies report treatment failure, notably againstStaphylococcus aureus. The aim of this study was to identify the features of daptomycin and its target bacteria that lead to daptomycin treatment failure. We show that daptomycin bactericidal activity againstS. aureusvaries significantly with the growth state and strain, according to the membrane fatty acid composition. Daptomycin efficacy as an antibiotic relies on its ability to oligomerize within membranes and form pores that subsequently lead to cell death. Our findings ascertain that daptomycin interacts with tolerant bacteria and reaches its membrane target, regardless of its bactericidal activity. However, the final step of pore formation does not occur in cells that are daptomycin tolerant, strongly suggesting that it is incapable of oligomerization. Importantly, membrane fatty acid contents correlated with poor daptomycin bactericidal activity, which could be manipulated by fatty acid addition. In conclusion, daptomycin failure to treatS. aureusis not due to a lack of antibiotic-target interaction, but is driven by its capacity to form pores, which depends on membrane composition. Manipulation of membrane fluidity to restoreS. aureusdaptomycin bactericidal activityin vivocould open the way to novel antibiotic treatment strategies.

show abstract

Section: Resultsmentioning

confidence: 92%

mentioning

confidence: 99%

Impact of Bacterial Membrane Fatty Acid Composition on the Failure of Daptomycin To Kill Staphylococcus aureus

Boudjemaa

Cabriel

Dubois‐Brissonnet

et al. 2018

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…As swarming is reported to be a stage connected to biofilm formation, we hypothesize that the presence of SFAs-and, thus, membrane fluidity-may also play a role in biofilm formation (19,68). A recent study demonstrated that cells of Staphylococcus aureus, L. monocytogenes, P. aeruginosa, and Salmonella enterica serovar Typhimurium in biofilms are enriched in SFAs compared to planktonic cells (69). Our studies focus on the effects of phospholipid composition of cells in relatively early stages of biofilm development.…”

Section: Discussionmentioning

confidence: 94%

Rcs Phosphorelay Activation in Cardiolipin-Deficient Escherichia coli Reduces Biofilm Formation

2019

View full text Add to dashboard Cite

Biofilm formation is a complex process that requires a number of transcriptional, proteomic, and physiological changes to enable bacterial survival. The lipid membrane presents a barrier to communication between the machinery within bacteria and the physical and chemical features of their extracellular environment, and yet little is known about how the membrane influences biofilm development. We found that depleting the anionic phospholipid cardiolipin reduces biofilm formation in Escherichia coli cells by as much as 50%. The absence of cardiolipin activates the regulation of colanic acid synthesis (Rcs) envelope stress response, which represses the production of flagella, disrupts initial biofilm attachment, and reduces biofilm growth. We demonstrate that a reduction in the concentration of cardiolipin impairs translocation of proteins across the inner membrane, which we hypothesize activates the Rcs pathway through the outer membrane lipoprotein RcsF. Our study demonstrates a molecular connection between the composition of membrane phospholipids and biofilm formation in E. coli and suggests that altering lipid biosynthesis may be a viable approach for altering biofilm formation and possibly other multicellular phenotypes related to bacterial adaptation and survival. IMPORTANCE There is a growing interest in the role of lipid membrane composition in the physiology and adaptation of bacteria. We demonstrate that a reduction in the anionic phospholipid cardiolipin impairs biofilm formation in Escherichia coli cells. Depleting cardiolipin reduced protein translocation across the inner membrane and activated the Rcs envelope stress response. Consequently, cardiolipin depletion produced cells lacking assembled flagella, which impacted their ability to attach to surfaces and seed the earliest stage in biofilm formation. This study provides empirical evidence for the role of anionic phospholipid homeostasis in protein translocation and its effect on biofilm development and highlights modulation of the membrane composition as a potential method of altering bacterial phenotypes related to adaptation and survival.

show abstract

“…ATP levels are likely low in the ΔscmR strain (SI Appendix, Table S5). Furthermore, biofilm construction is enhanced in the mutant (SI Appendix, Table S7), and this process requires fatty acids (37,38), which may be siphoned away from AHL synthesis, again resulting in lower levels of AHL. Together, the AHL quantification studies further underline the role of QS in silencing biosynthetic genes and curbing secondary metabolism at high cell densities.…”

Section: Resultsmentioning

confidence: 99%

Discovery of scmR as a global regulator of secondary metabolism and virulence in Burkholderia thailandensis E264

Mao

Bushin

Moon

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

140

View full text Add to dashboard Cite

Bacteria produce a diverse array of secondary metabolites that have been invaluable in the clinic and in research. These metabolites are synthesized by dedicated biosynthetic gene clusters (BGCs), which assemble architecturally complex molecules from simple building blocks. The majority of BGCs in a given bacterium are not expressed under normal laboratory growth conditions, and our understanding of how they are silenced is in its infancy. Here, we have addressed this question in the Gram-negative model bacterium Burkholderia thailandensis E264 using genetic, transcriptomic, metabolomic, and chemical approaches. We report that a previously unknown, quorum-sensing-controlled LysR-type transcriptional regulator, which we name ScmR (for secondary metabolite regulator), serves as a global gatekeeper of secondary metabolism and a repressor of numerous BGCs. Transcriptionally, we find that 13 of the 20 BGCs in B. thailandensis are significantly (threefold or more) upor down-regulated in a scmR deletion mutant (ΔscmR). Metabolically, the ΔscmR strain displays a hyperactive phenotype relative to wild type and overproduces a number of compound families by 18-to 210-fold, including the silent virulence factor malleilactone. Accordingly, the ΔscmR mutant is hypervirulent both in vitro and in a Caenorhabditis elegans model in vivo. Aside from secondary metabolism, ScmR also represses biofilm formation and transcriptionally activates ATP synthesis and stress response. Collectively, our data suggest that ScmR is a pleiotropic regulator of secondary metabolism, virulence, biofilm formation, and other stationary phase processes. A model for how the interplay of ScmR with pathwayspecific transcriptional regulators coordinately silences virulence factor production is proposed.biosynthetic gene clusters | natural products | Burkholderia thailandensis | regulation | virulence

show abstract

The Biofilm Lifestyle Involves an Increase in Bacterial Membrane Saturated Fatty Acids

Cited by 83 publications

References 33 publications

Impact of Bacterial Membrane Fatty Acid Composition on the Failure of Daptomycin To Kill Staphylococcus aureus

Impact of Bacterial Membrane Fatty Acid Composition on the Failure of Daptomycin To Kill Staphylococcus aureus

Rcs Phosphorelay Activation in Cardiolipin-Deficient Escherichia coli Reduces Biofilm Formation

Discovery of scmR as a global regulator of secondary metabolism and virulence in Burkholderia thailandensis E264

Contact Info

Product

Resources

About