Abstract
Aspirin has provided clear benefits to human health. But salicylic acid (SAL) -the main aspirin biometabolite- exerts several effects on eukaryote and prokaryote cells. SAL can affect, for instance, the expression of Staphylococcus aureus virulence factors. SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation of S. aureus biofilm. The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify the S. aureus metabolism and/or metabolic regulators thus changing the expression of the main polysaccharides involved in biofilm formation. The exposure of biofilm to 2 mM SAL induced a 27% reduction in the intracellular free Fe2+ concentration compared with the controls. In addition, SAL depleted 23% of the available free Fe2+ cation in culture media. These moderate iron-limited conditions promoted an intensification of biofilms formed by strain Newman and by S. aureus clinical isolates related to the USA300 and USA100 clones. The slight decrease in iron bioavailability generated by SAL was enough to induce the increase of PIA expression in biofilms formed by methicillin-resistant as well as methicillin-sensitive S. aureus strains. S. aureus did not produce capsular polysaccharide (CP) when it was forming biofilms under any of the experimental conditions tested. Furthermore, SAL diminished aconitase activity and stimulated the lactic fermentation pathway in bacteria forming biofilms. The polysaccharide composition of S. aureus biofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in a codY-dependent manner. Moreover, SAL negatively affected codY transcription in mature biofilms thus relieving the CodY repression of the ica operon. Treatment of mice with SAL induced a significant increase of S aureus colonization. It is suggested that the elevated PIA expression induced by SAL might be responsible for the high nasal colonization observed in mice. SAL-induced biofilms may contribute to S. aureus infection persistence in vegetarian individuals as well as in patients that frequently consume aspirin.
Highlights
Staphylococcus aureus is a common commensal of the human nostrils (Kaspar et al, 2016)
Similar results were obtained by measuring the total free iron present in TSB supplemented with 0.25% of glucose (TSBg) (39.3 ± 7.1 μM) and TSBg with 5 mM of Salicylic acid (SAL) (21.4 ± 5.3 μM) by atomic absorption spectroscopy
The intracellular free Fe2+ concentration in S. aureus forming biofilms when grown in TSBg with 2 mM of SAL was 27% lower than that obtained in the control without SAL addition, and similar to that observed in TSBg treated with Chelex-100 (Figure 2)
Summary
Staphylococcus aureus is a common commensal of the human nostrils (Kaspar et al, 2016). In S. aureus, the extracellular matrix is composed of proteins, DNA and the polysaccharide intercellular adhesin (PIA). The amount of these matrix components may vary according to the surrounding environmental conditions (Furukawa et al, 2006). The PIA and CP synthesis depends upon the tricarboxylic acid (TCA) cycle and the expression of both polysaccharides is opposite in iron-deficient conditions (Vuong et al, 2005; Sadykov et al, 2010a). At this point it is worth mentioning that the TCA cycle is regulated by Fur (ferric uptake regulator) in an iron-dependent manner and by CodY, among other transcriptional factors (Richardson et al, 2015)
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