Tag Archives: carbapenemases

“Clavulanic Acid and Treasure Hunting”

Antimicrobial Resistance,

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….

Michael

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

“Carbapenemases: As old as the Hills..”

History of Microbiology, The Science of Microbiology, , ,

There has been a lot in the press recently about carbapenem resistant enterobacteraciae (CRE).

As people with a professional interest in infection, it is important we know in detail the origins of carbapenems and carbapenemases. Such knowledge and understanding also focuses the mind when trying to control them.

"Meropenem molecule"
“Meropenem molecule”

Carbapenems are derived from Thienamycin, a naturally occuring substance found in Streptomyces cattleya, which is a bacteria found commonly in soil in the environment. Other bacteria residing close to these carbapenem like substances in the environment thus have to protect themselves to avoid being destroyed. Thus carbapenemases evolved in other environmental bacteria such as Bacillus cereus, Bacillus anthracis and Shewanella, amongst others.

What we have done is take these naturally occuring compounds, purified them (with only very minor modifications), concentrated them and started administering them to humans in the form of carbapenem antibiotics, thus ramping up the selection pressure on the human bacterial flora.

It is thus not surprising that human enterobacteraciae, faced with this selection pressure have decided that they want defences against carbapenems, and have “acquired” the resistance genes from the environmental bacteria, most likely by transfer on mobile genetic elements.

Many people still perceive carbapenemases as being a relatively new phenomenen. We know that they are not new however. Both carbapenems and carbapenemases have probably been around for millions of years. We have just moved the battle between carbapenems and carbapenemases from the “hills” into the human flora, where it really matters….

Michael

Off camping this weekend!, I will write a short article next week sometime on “protecting the carbapenems”.