The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus

Abstract

is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying virulence modulation by antibiotics were reviewed. The relevance of observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease.

β-lactam Antibiotics Stimulate the Pathogenicity of Methicillin-resistant Staphylococcus aureus Via SarA-controlled Tandem Lipoprotein Expression

“…It is reported that the subinhibitory concentrations of β-lactam antibiotics can induce the production of some S. aureus toxins, such as alpha-toxin [12], PVL [2], and enterotoxins [13], or immune evasion molecules, such as SPA [14]. Here, S. aureus N315, which is a globally prevalent sequence type 5 (ST5) MRSA strain [21], was tested for its antibiotic response to identify new factors contributing to MRSA pathogenesis in antibiotic induction.…”

“…β-lactams as antibiotics block the cell wall synthesis of bacteria to exert antimicrobial effects. By contrast, β-lactams as inductors may trigger global regulatory networks to modulate virulence in S. aureus [13]. RT-qPCR revealed that the expression of global regulators, including sarA, agrA, RNAIII, rot, ccpA, and saeR , increased in OXA-treated N315 compared with those in the untreated ones (Fig 6A).…”

“…It has been reported that between 30% and 80% of individuals infected with MRSA are inappropriately treated often with β-lactam antibiotics because of the failure to recognize MRSA infection initially [10,11]. Accumulated data have demonstrated that the subinhibitory concentrations of β-lactam antibiotics can promote S. aureus pathogenicity by increasing the expression of alpha-toxin [12], Panton-Valentine leukocidin (PVL) [2], enterotoxins [13], or staphylococcal protein A (SPA) in vitro [14]. Nevertheless, the contribution of the certain altered virulence factor to the MRSA pathogenesis in vivo has yet determined, and the molecular mechanisms underlying β-lactams modulating MRSA pathogenesis remain largely unknown.…”

Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

“…Antibiotics may, therefore, inhibit some detrimental effects of infection without necessarily reducing the bacterial burden. Indeed, subinhibitory concentrations of antibiotics modulate the expression of global virulence loci in S. aureus (i.e., SarA , Sae , and Agr ) . The resulting changes in the profile of secreted virulence factors may lead to a reduced impact on tissue degradation or cell cytotoxicity .…”

“…Indeed, subinhibitory concentrations of antibiotics modulate the expression of global virulence loci in S. aureus (i.e., SarA, Sae, and Agr). 111 The resulting changes in the profile of secreted virulence factors may lead to a reduced impact on tissue degradation or cell cytotoxicity. 40,112,113 Alternatively, it is possible that antibiotics initially reduce the bacterial burden, allowing bone healing to be initiated before the infection reactivates.…”