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Understanding how Staphylococcus epidermidis adapts to nitrosative stress generated by the cells of innate immunity
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Staphylococcus epidermidis is an opportunistic pathogen that colonizes the human skin and mucosa. When it has the chance, this bacterium adheres to indwelling biodevices where it starts the formation of a biofilm. Biofilms are functional communities of microbial cells surrounded by a complex self-produced extracellular matrix of polymeric substances, which act as a shield against the host immune system and antibiotics. Macrophages, which produce the antimicrobial NO, are among the first cells to be recruited to fight biofilm infections. However, questions such as how biofilms respond to NO and, in particular, how S. epidermidis biofilms adapt to NO remain unexplored. In this work, we performed targeted metabolite profiling analysis and biofilm composition determination to uncover how S. epidermidis biofilms survive the deleterious action of NO. We observed that NO significantly inhibits biofilm production in two strong biofilm producers, namely 1457 and RP62A strains, but not that in 1457-M12, a weak biofilm producer. Moreover, we showed that the lower biofilm amounts (2-fold) produced in 1457 exposed to NO, are most likely due to the deleterious effect of NO on biofilm matrix proteins and number of viable cells, 2- and 4-fold less than in untreated biofilms, respectively. In RP62A, the lower biofilm amounts in the presence of NO can be explained by a significant decrease (4-fold) in cell viability. Additionally, our metabolic data indicated that resistance of biofilm-producing strains to NO was achieved through an increase in the activity of glycolysis and lactate dehydrogenase, and inhibition of several enzymes at the pyruvate node, TCA cycle, amino-sugar metabolism, and PIA synthesis. To further elucidate this behavior, the optimization of an intracellular metabolite extraction protocol was initiated.
Overall, this work contributed to the advance of knowledge on how biofilms, which are a major cause of antibiotic-resistant infections, resist NO stress of the innate immunity.
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Staphylococcus epidermidis biofilm nitrosative stress central carbon metabolism