[SCAN] Proteomics of Non-Model Organisms Lab

Title: Adaptation of Staphylococcus epidermidis to antimicrobial skin fatty acids: a multi-omics study

Speaker: Ana Coelho

From: Proteomics of Non-Model Organisms Lab, ITQB NOVA

Abstract: Staphylococcus epidermidis (SE), a human skin colonizer, is an opportunistic pathogen mainly associated with medical device infections. Phylogenetically, SE strains are clustered into lineage A/C, which includes strains isolated from infections and the colonization of healthy individuals, and lineage B, comprising mainly colonization isolates. Better understanding SE pathogenicity mechanisms is necessary to develop efficient strategies to prevent and treat challenging SE infections. Human skin, a key player in the innate immune system, releases compounds with antimicrobial properties, such as fatty acids (FAs). Using representative strains from each lineage we studied: 1) FAs as selective antimicrobials against the A/C strain using bacterial growth inhibition and cytotoxicity assays; and 2) the mechanism of action of lauric acid (LA); and 3) SE adaptation using proteomics and 1HNMR metabolomics.

The A/C strain showed a higher susceptibility to FAs, and LA was the most promising selective antimicrobial FA tested. Furthermore, no cytotoxicity for LA was found on a 3D reconstructed human epidermis model. Intracellular proteomics and metabolomics results propose that during prolonged LA exposure, B strain employs a coordinated adaptation strategy encompassing metabolic reprogramming, stress response management, and virulence factor modulation, ultimately prioritizing survival over cell proliferation. Time-course 1HNMR-based exometabolomics revealed pyruvate accumulation for B strain under LA stress. Under these conditions, our results suggest that rapid growth is supported by ATP generation, which aids adaptation to LA while sustaining biomass production. For A/C strain, LA stress increased glucose uptake, suggesting an increased glycolytic flux with carbon flow predominantly directed toward acetate production. Our data support the use of ATP-dependent chaperones as major players in the adaptation of S. epidermidis strains to LA.

Overall, this study highlights the potential use of LA as a topical formulation for the selective growth inhibition of SE pathogenic strains.

SCANs are weekly seminars that happen every Wednesday at noon by in-house researchers and invited speakers at ITQB NOVA.