Clavulanic acid. It’s not an antibiotic in the classical sense of the word, but where would be without it? Probably one of the most important discoveries in the history of antibiotic development.
Clavulanic acid, or potassium clavulanate, was discovered in the early 1970s by scientists at Beecham pharmaceuticals. Produced naturally by the bacterium Streptomyces clavuligerus, it is a potent inhibitor of (Class A) beta-lactamases.
We know that Streptomyces are soil bacteria and there are hundreds of different Streptomyces species recorded in the taxonomy. A majority of Streptomyces species produce beta-lactam antibiotics and a lot of them also produce beta-lactamases, showing the lengths that these bacteria would go to to survive amongst other streptomyces and also other micro-organisms living in close proximity
It is interesting therefore that one of the Streptomyces species (Streptomyces clavuligerus) had the “brains” to produce a beta-lactamase inhibitor. Why? This would have given the bacterium a selection advantage aginst other beta-lactamase producing Streptomyces in a beta-lactam rich environment, in a sense “dis-arming” its competitors.
For Streptomyces clavuligerus, it is thus impressive that it has produced a third line of defence after beta-lactams and beta-lactamases, demonstrating just how sophisticated antibiotic defences are amongst soil streptomyces.
We have obviously taken full advantage of this from a clinical point of view. By combining clavulanic acid with penicillins such as amoxycillin (co-amoxyclav) or ticarcillin (co-ticarclav), it extends antimicrobial activity way beyond what is afforded by the penicillin alone.
This takes my thoughts onto the major clinical problem of carbapenemases. We know that carbapenems (often produced naturally by Streptomyces) and carbapenemases (often originating in Bacillus species) occur naturally. It is thus highly possible, even probable, that carbapenemase inhibitors are also present in the environment. We just have to find them.
Bacteria will go to extraordinary lengths to ensure their own survival….
For a nice article on cutting edge research being done with beta-lactamases, click here. It also includes the Ambler classification of beta-lactamases, which I often read, then forget, then read again, then forget…..and so on!
For another related article on carbapenemases, click here