The Active Component of Aspirin, Salicylic Acid, PromotesStaphylococcus aureusBiofilm Formation in a PIA-dependent Manner.
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 ofStaphylococcus aureusvirulence factors. SAL can also form complexes with iron cations and it has been shown that different iron chelating molecules diminished the formation ofS. aureusbiofilm. The aim of this study was to elucidate whether the iron content limitation caused by SAL can modify theS. aureusmetabolism 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 byS. aureusclinical 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-sensitiveS. aureusstrains.S. aureusdid 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 ofS. aureusbiofilms was examined and FTIR spectroscopic analysis revealed a clear impact of SAL in acodY-dependent manner. Moreover, SAL negatively affectedcodYtranscription in mature biofilms thus relieving the CodY repression of theicaoperon. Treatment of mice with SAL induced a significant increase ofS aureuscolonization. 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 toS. aureusinfection persistence in vegetarian individuals as well as in patients that frequently consume aspirin.
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Instituto de Investigaciones en Microbiología y Parasitología Médica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires Buenos Aires, Argentina.
Cristian
C
Dotto
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Instituto de Investigaciones en Microbiología y Parasitología Médica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires Buenos Aires, Argentina.
Andrea
A
Lombarte Serrat
Facultad de Ciencias Exactas, Centro de Investigación y Desarrollo de Fermentaciones Industriales (CINDEFI), Centro Científico Technológico Consejo Nacional de Investigaciones Científicas y Tócnicas (CTT CONICET La Plata), Universidad Nacional de La Plata La Plata, Argentina.
Natalia
N
Cattelan
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Instituto de Investigaciones en Microbiología y Parasitología Médica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires Buenos Aires, Argentina.
María S
MS
Barbagelata
Facultad de Ciencias Exactas, Centro de Investigación y Desarrollo de Fermentaciones Industriales (CINDEFI), Centro Científico Technológico Consejo Nacional de Investigaciones Científicas y Tócnicas (CTT CONICET La Plata), Universidad Nacional de La Plata La Plata, Argentina.
Osvaldo M
OM
Yantorno
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Instituto de Investigaciones en Microbiología y Parasitología Médica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires Buenos Aires, Argentina.
Daniel O
DO
Sordelli
Functional Microbiology, Institute for Microbiology, University of Veterinary Medicine Vienna, Austria.
Monika
M
Ehling-Schulz
Functional Microbiology, Institute for Microbiology, University of Veterinary Medicine Vienna, Austria.
Tom
T
Grunert
Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Instituto de Investigaciones en Microbiología y Parasitología Médica, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires Buenos Aires, Argentina.
Fernanda R
FR
Buzzola
MRSA; PIA; Staphylococcus aureus; biofilm; codY; iron; salicylic acid