How does clindamycin inhibit toxin production by Group A Strep and Staphylococcus aureus (both MSSA and MRSA)?
Answer: The toxins are proteins. Translation of mRNA to make proteins happens on the ribosomes. Clindamycin blocks the ribosomes (it’s an anti-ribosomal antibiotic). That’s how it inhibits toxin production. Linezolid, which also binds to the 50s subunit does the same thing. See the journal of infectious disease article cited below.
KTA: [Clindamycin doesn’t bind to the toxin. Antibiotics that inhibit cell wall synthesis do so slowly while all the while, the bacteria can still synthesize toxins. I personally hypothesize that it would be natural for the bacteria to ramp up toxin production when it’s cell wall is being attacked. It has to fight back!]
Penicillin (PCN) works by inhibiting bacterial cell wall synthesis and replication. Clindamycin binds to the 50s ribosomal subunit and inhibits protein synthesis. As such, clindamycin “shuts down production of toxins”. Clindamycin or clindamycin + PCN are advocated for devastating streptococcal soft tissue infections including necrotizing fasciitis, myositis and toxic shock syndrome (TSS) (NEJM 334: 240, 1996).
“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” J Infect Dis. 2007 Jan 15;195(2):202-11
Notice that “in a prokaryotic cell, transcription and translation are coupled; that is, translation begins while the mRNA is still being synthesized. In a eukaryotic cell, transcription occurs in the nucleus, and translation occurs in the cytoplasm.” Notice that translation happens on the ribosomes and transcription happens on the DNA or RNA. Click here to see depiction.
Important Links
References
https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540131/all/Clindamycin
NEJM 334: 240, 1996. http://www.nejm.org/doi/full/10.1056/NEJM199601253340407
J Infect Dis. 2007 Jan 15;195(2):202-11. https://www.ncbi.nlm.nih.gov/pubmed/17191165