Impact of Antibiotics on Expression of Virulence‐Associated Exotoxin Genes in Methicillin‐Sensitive and Methicillin‐ResistantStaphylococcus aureus

Abstract

Extracellular protein toxins contribute to the pathogenesis of a wide variety of Staphylococcus aureus infections. The present study investigated the effects that cell-wall active antibiotics and protein-synthesis inhibitors have on transcription and translation of genes for Panton-Valentine leukocidin, alpha-hemolysin, and toxic-shock syndrome toxin 1, in both methicillin-sensitive and methicillin-resistant S. aureus. Subinhibitory concentrations of nafcillin induced and prolonged mRNA for Panton-Valentine leukocidin, alpha-toxin, and toxic-shock syndrome toxin 1 and increased toxin production. In contrast, clindamycin and linezolid markedly suppressed translation, but not transcription, of toxin genes. These results suggest (1) that protein-synthesis inhibition is an important consideration in the selection of antimicrobial agents to treat serious infections caused by toxin-producing gram-positive pathogens and (2) that, by inducing and enhancing toxin production, inadvertent use of beta-lactam antibiotics to treat methicillin-resistant S. aureus infections may contribute to worse outcomes.

The role of virulence determinants in community-associated MRSA pathogenesis

“…Notwithstanding the compelling epidemiological linkage between PVL and CA-MRSA strains, is there anything overlooked when analyzing the contribution of PVL to the pathogenesis of CA-MRSA? For example, PVL may be produced in abundance in the human host, perhaps in the context of antibiotic-induced bacterial SOS response that could result in prophage induction and enhanced expression of phage-encoded PVL [60,61]. Also, PVL may harm human cells other than leukocytes in a yet undiscovered interaction, which in this case would have to be human-specific, as mouse and rabbit infection models clearly do not show a PVL effect.…”

Socially mediated induction and suppression of antibiosis during bacterial coexistence

“…First, antibiotic concentrations in soil are believed to be too low to kill or inhibit competing bacteria (9). Second, subinhibitory (sub-MIC) concentrations of antibiotics induce responses in exposed organisms, such as increased biofilm formation (14) or expression of virulence genes (11,15) that may benefit these target cells (10). Thus, rather than weapons, these arguments have led to the idea that antibiotics are cooperative signals (16) used for intercellular communication, that they are "collective regulators of the homeostasis of microbial communities" (12).…”

Neumonía necrosante por Staphylococcus aureus extrahospitalario resistente a la meticilina:reporte de dos casos en Colombia

“…El uso de linezolide en la neumonía necrosante por SARM extrahospitalario puede tener un valor agregado que consiste en suprimir la expresión de la toxina PVL, α-hemolisina y TSST-1 (toxic shock síndrome toxin 1) (26). Esto último parece sugerir que, en todo caso, el uso de vancomicina como monoterapia puede no ser suficiente y habrá que considerar, inclusive, la asociación con otros medicamentos, como linezolide o clindamicina, además de garantizar un adecuado drenaje del foco.…”