Salicylic Acid DiminishesStaphylococcus aureusCapsular Polysaccharide Type 5 Expression

Abstract

Capsular polysaccharides (CP) of serotypes 5 (CP5) and 8 (CP8) are major Staphylococcus aureus virulence factors. Previous studies have shown that salicylic acid (SAL), the main aspirin metabolite, affects the expression of certain bacterial virulence factors. In the present study, we found that S. aureus strain Reynolds (CP5) cultured with SAL was internalized by MAC-T cells in larger numbers than strain Reynolds organisms not exposed to SAL. Furthermore, the internalization of the isogenic nonencapsulated Reynolds strain into MAC-T cells was not significantly affected by preexposure to SAL. Pretreatment of S. aureus strain Newman with SAL also enhanced internalization into MAC-T cells compared with that of untreated control strains. Using strain Newman organisms, we evaluated the activity of the major cap5 promoter, which was significantly decreased upon preexposure to SAL. Diminished transcription of mgrA and upregulation of the saeRS transcript, both global regulators of CP expression, were found in S. aureus cultured in the presence of SAL, as ascertained by real-time PCR analysis. In addition, CP5 production by S. aureus Newman was also decreased by treatment with SAL. Collectively, our data demonstrate that exposure of encapsulated S. aureus strains to low concentrations of SAL reduced CP production, thus unmasking surface adhesins and leading to an increased capacity of staphylococci to invade epithelial cells. The high capacity of internalization of the encapsulated S. aureus strains induced by SAL pretreatment may contribute to the persistence of bacteria in certain hosts.Staphylococcus aureus is an opportunistic pathogen that causes both community-acquired and life-threatening nosocomial infections (35). Although S. aureus can colonize mucosal surfaces of healthy humans, it is also a major cause of skin and soft tissue infections and has the invasive potential to cause severe infections, including osteomyelitis, endocarditis, and bacteremia with metastatic complications (35). The pathogenicity of S. aureus depends upon successful adaptation of the microorganism to the host and the coordinated expression of virulence factors. S. aureus is usually surrounded by a thin capsule, and capsular polysaccharides (CP) of serotypes 5 (CP5) and 8 (CP8) are the most prevalent ones in clinical isolates from humans (40). S. aureus CP5 and CP8 are antiphagocytic and positively contribute to the virulence of this pathogen (27, 40). Production of CP5 (or CP8) may be deeply modified by different global regulators (agr, arlRS, saeRS, and sarA) and transcriptional factors (mgrA, B ) (30,31,34,55,59). A recent report has shown that the sbcDC locus mediates repression of CP5 production as a part of the SOS response in S. aureus (5). Furthermore, the expression of CP5 (7) is highly sensitive to diverse environmental signals, such as iron concentration, specific nutrients, CO 2 concentration, or subinhibitory concentrations of ciprofloxacin and mitomycin C (5,17,26,40).Aspirin is a nonsteroidal anti-inflammatory agent that is...

The Active Component of Aspirin, Salicylic Acid, Promotes Staphylococcus aureus Biofilm Formation in a PIA-dependent Manner

“…As shown in Figure 6A, SAL treatment of planktonic cultures of the Newman strain caused a perturbation of the surface polysaccharide composition that was not reverted by iron addition. In the light of our previous work and the results described herein it is suggested that CP instead of PIA expression is affected by SAL treatment due to the fact that CP production under planktonic culture conditions is limited (Alvarez et al, 2010). In contrast to planktonic growth, PCA of the Newman biofilms revealed that iron limitation by SAL exposure induced polysaccharide production alterations that were partially reverted by iron addition (Figure 6B).…”

“…The expression of virulence factors and regulatory genes is modified by SAL in several bacterial species (Pomposiello et al, 2001; Denkin et al, 2005). Previous findings from our laboratory demonstrated that exposure of encapsulated S. aureus strains to low concentrations of SAL reduced CP production and increased the Eap adhesin expression under planktonic conditions (Alvarez et al, 2010, 2011). On the other hand, Johnson et al (2008) observed that an increase of Eap expression under depleted iron conditions contributed to biofilm formation, a finding that becomes relevant due to the fact that SAL can form complexes with iron cations (Cheng et al, 1996; Pozdnyakov et al, 2015).…”

“…In our previous work it was demonstrated that CP expression is reduced when planktonic S. aureus is grown in the presence of low concentrations of SAL (Alvarez et al, 2010). Thus, to establish the effect of iron chelation by SAL on S. aureus surface polysaccharides, chemometric-assisted FTIR spectroscopic measurements were performed from S. aureus planktonic cultures and biofilms.…”

“…The number of copies of each sample transcript was determined with the aid of the 7500 system SDS software (Applied Biosystems, Carlsbad, CA, USA). The 2 −ΔΔCt value represents the difference in threshold cycle (Ct) between the target and control ( gyrB ) genes treated with SAL or SAL with Fe 2+ , minus the difference in Ct between untreated (TSBg) target and control genes (Alvarez et al, 2010). …”

Rapid and Reliable Identification of Staphylococcus aureus Capsular Serotypes by Means of Artificial Neural Network-Assisted Fourier Transform Infrared Spectroscopy

“…Preimmune rabbit serum and absorbed sera were nonreactive by immunodiffusion against bacterial extracts containing CP5 and CP8. Isolates that were nonreactive in the colony immunoblot assay were confirmed to be NT by the double immunodiffusion assay, using the capsule extracts as previously described (35). Briefly, a 1% agarose gel was prepared on a glass slide and wells were punched in a circular fashion around a central hole.…”