Abstract
Biofilms are communities of microorganisms attached to a surface or each other. Biofilm-associated cells are the etiologic agents of recurrent Staphylococcus aureus infections. Infected human tissues are hypoxic or anoxic. S. aureus increases biofilm formation in response to hypoxia, but how this occurs is unknown. In the current study we report that oxygen influences biofilm formation in its capacity as a terminal electron acceptor for cellular respiration. Genetic, physiological, or chemical inhibition of respiratory processes elicited increased biofilm formation. Impaired respiration led to increased cell lysis via divergent regulation of two processes: increased expression of the AtlA murein hydrolase and decreased expression of wall-teichoic acids. The AltA-dependent release of cytosolic DNA contributed to increased biofilm formation. Further, cell lysis and biofilm formation were governed by the SrrAB two-component regulatory system. Data presented support a model wherein SrrAB-dependent biofilm formation occurs in response to the accumulation of reduced menaquinone.
Highlights
Staphylococcus aureus is a commensal bacterium that is estimated to colonize between 20–50% of the healthy human population (Naimi et al, 2003; Graham et al, 2006; Enright et al, 2002; Ohara-Nemoto et al, 2008; Zafar et al, 2007)
Biofilm formation was examined in diverse S. aureus isolates that vary in their ability to form biofilms (LAC, SH1000, MW2, N315)
Previous work found that hypoxic growth results in increased biofilm formation of S. aureus
Summary
Staphylococcus aureus is a commensal bacterium that is estimated to colonize between 20–50% of the healthy human population (Naimi et al, 2003; Graham et al, 2006; Enright et al, 2002; Ohara-Nemoto et al, 2008; Zafar et al, 2007). The dominant fraction of invasive infections caused by this bacterium occur in the context of bacteremia (Klevens et al, 2007). S. aureus can infect and cause diseases of the lungs (penumonia), skin (cellulitis), skeletal tissues (ostoemyelitis), and heart tissue (endocarditis), as well as septic shock (Klevens et al, 2007; Tong et al, 2015). While bacteremia and endocarditis infections have a lower degree of mortality, they are associated with a higher degree of recurrence, suggestive of therapeutic recalcitrance (Klevens et al, 2007). A recent epidemiological analysis of ~8,700 cases of invasive S. aureus infections in the US found that nearly 92% cases required hospitalization (Klevens et al, 2007)
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