Biology subjects

Kengmo Tchoupa, A.

Publications and source records attributed to Kengmo Tchoupa, A..

3 recordsLinked to original sources

bioRxiv2023

Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus

Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was more common in blood and nose isolates than in skin strains, suggesting a particularly important role of Lip2 for skin colonization. Accordingly, in a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid - a human-specific AFA - in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth. Our data support a model in which S. aureus exploits and/or exacerbates lipid disorders to colonize otherwise inhospitable niches.

microbiology↗

bioRxiv2022

Prokaryotic phospholipid translocation by ubiquitous PplT domain proteins

Flippase proteins exchanging phospholipids between the cytoplasmic membrane leaflets have been identified in Eukaryotes but remained largely unknown in Prokaryotes. Only MprF proteins that synthesize aminoacyl phospholipids in some bacteria have been found to contain a domain that translocates the produced lipids. We show here that this domain, which we named prokaryotic phospholipid translocator (PplT), is widespread in Bacteria and Archaea, encoded as a separate protein or fused to different types of enzymes. We also demonstrate that the Escherichia coli PplT protein interacts with many phospholipid-synthetic enzymes and deletion of pplT impaired bacterial growth, which supports its potential role in membrane lipid metabolism. PplT domain proteins may be general prokaryotic lipid flippases with critical roles in cellular homeostasis.

microbiology↗

bioRxiv2019

The type VII secretion system protects Staphylococcus aureus against antimicrobial host fatty acids

The Staphylococcus aureus type VII secretion system (T7SS) exports several proteins that are pivotal for bacterial virulence. The mechanisms underlying T7SS-mediated staphylococcal survival during infection nevertheless remain unclear. Here we show that the absence of EsxC, a small secreted effector implicated in bacterial persistence, results in cell membrane defects in S. aureus. Interestingly, isogenic mutants lacking EsxC, other T7SS effectors EsxA and EsxB, or the membrane-bound ATPase EssC, are more sensitive to killing by the host-derived antimicrobial fatty acid, linoleic acid (LA), compared to the wild-type (WT). LA induces more cell membrane damage in the T7SS mutants compared to the WT. Although WT and mutant strains did not differ in their ability to bind labelled LA, membrane lipid profiles show that T7SS mutants are less able to incorporate LA into their membrane phospholipids. Furthermore, proteomic analyses of WT and mutant cell fractions reveal that, in addition to compromising membranes, T7SS defects induce oxidative stress and hamper their response to LA challenge. Thus, our findings indicate that T7SS is crucial for S. aureus membrane integrity and homeostasis, which is critical when bacteria encounter antimicrobial fatty acids.

microbiology↗