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Dynamic exometabolomics reveals metabolic adaptations of Staphylococcus epidermidis to pH-mimicking skin and bloodstream

Elisabete Morais,Ana M. Gil,M. Miragaia,Luís G. Gonçalves,A. V. Coelho

Published 2025 in bioRxiv

ABSTRACT

Staphylococcus epidermidis (SE) is a common human skin coloniser, which is often the cause of medical device-associated infections. SE population is composed of two clonal lineages, A/C and B, with distinct pathogenic potential. Although pH is known to change during infection when SE crosses the host skin to access the bloodstream, the impact of this pH alteration on SE pathogenicity is poorly understood. Recognizing how SE deals with pH increments will help designing effective prevention and treatment strategies against SE infections. To investigate the metabolic adaptations of representative A/C and B strains to different pH, we mimicked skin and blood pH conditions (5.5 and 7.4) and followed biomass formation, growth media pH and exometabolites over time. Although both strains share some metabolic patterns, specificities were identified for each strain and pH condition. The B strain was better adapted to use diverse carbon sources and at blood pH has a more active TCA cycle and amino acid catabolism. At blood pH, the B strain depletes formate from the extracellular media, while its extracellular accumulation by the A/C strain could work as a host invasion strategy. For both SE strains, TCA cycle regulation, purine biosynthesis and glutamate uptake could be associated with virulence, particularly biofilm production, especially relevant for ICE25 which is able to produce high adherence biofilm. The uptake and consumption of saccharides follow similar profiles and seem to be pH-regulated by both strains. The dynamic study of SE exometabolome has contributed to understanding the intracellular processes and their relationship with virulence.

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