Enterococcus faecalis Readily Adapts Membrane Phospholipid Composition to Environmental and Genetic Perturbation

Abstract

The bacterial lipid membrane, consisting both of fatty acid (acyl) tails and polar head groups, responds to changing conditions through alteration of either the acyl tails and/or head groups. This plasticity is critical for cell survival as it allows maintenance of both the protective nature of the membrane as well as functioning membrane protein complexes. Bacteria that live in fatty-acid rich environments, such as those found in the human host, can exploit host fatty acids to synthesize their own membranes, in turn, altering their physiology. Enterococcus faecalis is such an organism: it is a commensal of the mammalian intestine where it is exposed to fatty-acid rich bile, as well as a major cause of hospital infections during which it is exposed to fatty acid containing-serum. Within, we employed an untargeted approach to detect the most common phospholipid species of E. faecalis OG1RF via ultra-high performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). We examined not only how the composition responds upon exposure to host fatty acids but also how deletion of genes predicted to synthesize major polar head groups impact lipid composition. Regardless of genetic background and differing basal lipid composition, all strains were able to alter their lipid composition upon exposure to individual host fatty acids. Specific gene deletion strains, however, had altered survival to membrane damaging agents. Combined, the enterococcal lipidome is highly resilient in response to both genetic and environmental perturbation, likely contributing to stress survival.

C-phycocyanin alleviated cisplatin-induced oxidative stress and inflammation via gut microbiota—metabolites axis in mice

“…Enterococcus faecalis is a mammalian gut microbiota enriched in fatty acid-rich bile ( 45 ). Enterococcus faecalis , as a conditional pathogenic microorganism, changes into a pathogenic state when intestinal ecology is dysregulated, resulting in extensive infection ( 46 ).…”

Human serum induces daptomycin tolerance inEnterococcus faecalisand viridans group streptococci

“…In addition to peptidoglycan accumulation, serum-induced daptomycin tolerance in S. aureus occurs via an increase in cardiolipin abundance in the membrane. Therefore, we examined serum-induced daptomycin tolerance in E. faecalis mutant strains defective for one or both of the cardiolipin synthases (Δ cls1 , Δ cls2 ) and/or one of the two lysylphosphatidylglycerol synthases present in E. faecalis (Δ mprF2 ) [39].…”

Bacterial cell membranes and their role in daptomycin resistance: A review

“…DAP possesses a cyclic peptide core linked to a fatty acyl chain and requires calcium to adopt an amphipathic conformation that facilitates oligomerization and insertion into the bacterial membrane. In addition, complex formation with calcium masks the lipopeptides’s negative charge and increases its affinity for the membrane lipid PG, the major constituent of Gram-positive membranes (typically comprising 50%–65% of the total APL content in S. aureus and E. faecalis ( Müller et al, 2016 ; DeMars et al, 2020 ; Kotsogianni et al, 2021 ; Woodall et al, 2021 ). Recent structural analysis of Ca 2+ -DAP in lipid bilayers containing PG shows that DAP forms tetramers within the outer leaflet ( Beriashvili et al, 2020 ).…”

“…Interestingly, a different analysis of membrane lipids of the DAP-R E. faecalis strain performed by 2D-TLC during exponential growth showed a significant increase in PG, a reduction in CL, and no differences in lysyl-PG as compared to S613, while levels of GP-DGDAG were not reported ( Khan et al, 2019 ). Thus, lipid alterations other than a decrease in membrane PG are likely to also contribute to DAP-R. A recent study showed that the absence of CL in E. faecalis OG1RF, achieved by deletion of both CL synthases, increased sensitivity to DAP and other cell damaging agents such as SDS, while the absence of lysyl-PG, resulting from deletion of mprF2 , did not change sensitivity to DAP but rendered the mutant more resistant to SDS ( Woodall et al, 2021 ). The triple mutant, which lacked CL and lysyl-PG, restored membrane tolerance to DAP and SDS to the level of parental strain OG1RF.…”