Sunday, November 8, 2015

Genentech's Trojan horse destroys cocooned Staphylococcus aureus

Genentech did it again. It is truly amazing that since its inception in late 70s, Genentech, a bona fide biotech company, keeps its original spirit alive and encourages and supports R&D scientists to conduct and produce quality research befitting publication in top journals. I think in this regard Genentech does not have a single peer in whole of biotech industry.  


First, they showed that unlike freely floating extracellular S. aureus, intracellularly entrenched, hard to reach S. aureus are of clinical relevance


Indeed, in vitro experiments confirmed that intracellular S. aureus are resistance to conventional antibiotic application.


To overcome this resistance, Genentech's team designed antibody-antibiotic complex, called rifalogue, that was made of anti-S. aureus antibody and antibiotic rifampicin complex. The authors first showed that in vitro once rifalogue attached to S. aureus is internalized by cells rifampicin is released from complexes [in endosomes] and destroys S. aureus.


Finally, the authors confirmed effectiveness of this strategy against S. aureus in in vivo experiments as well.


In summary, these results (re)-opens the door for immunotherapy against infectious agents.

I would admit that for me data seems extremely clear-cut. This is a little bit concerning. I want to see these results confirmed in other labs. Another puzzling point is its mechanism of action. The model proposes that rifalogue works by engaging S. aureus with its Fab part and mammalian cells by its FcR. This suggests that rifalogue can't access or destroy S. aureus already cocooned within cells, but it could prevent freely floating S. aureus becoming intracellular. But regular rifampicin is capable of destroying freely floating S. aureus too. So this is a paradox for me [because results showed that rifalogue was still highly effective, even after delay of 24h, against "potentially" intracellular S. aureus]. 

David Usharauli

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