How do bacteria become resistant to beta lactams?
1 Answer
Some can produce an enzyme called beta lactamase that breaks down beta-lactam antibiotics.
Some efflux pump is also important
Explanation:
The way that beta-lactam antibiotics work is that they bind to to the enzyme that forms cell wall. (called D,D-transpeptidase). Beta-lactamase have a similar structure D,D-transpeptidase which allows it to bind to beta-lactam. But unlike D,D-transpeptidase, it can also break down the beta lactam.
Beta-lactamase relies mainly on the following amino acid residues to function:-
1) Lys73 OR Glu166 (unsure) - activate -CONH- group inside beta-lactam structure
2) Ser70 - nucleophilic attack on carbonyl group inside beta-lactam structure. The Serine - Lysine configuration is frequently referred to as Ser-X-X-Lys
3) possible - Ser130, Lys234 - protonation of nitrogen group inside beta-lactam structure
There are a variety of antibiotics. Other mechanism for other antibiotic resistance is through the use of protein pump called efflux pump.
CmeDEF-based efflux pump is associated with resistance to antibiotics like ampicillin (which is also a beta-lactam).
Although antibiotics are the most clinically important substrates of efflux systems, it is probable that most efflux pumps have other natural physiological functions. Examples include:
- The E. coli AcrAB efflux system, which has a physiologic role of pumping out bile acids and fatty acids to lower their toxicity.
- The MexXY component of the MexXY-OprM multidrug efflux system of P. aeruginosa is inducible by antibiotics that target ribosomes via the PA5471 gene product
The importance of efflux pumps in bacterial antibiotic resistance M. A. Webber and L. J. V. Piddock http://jac.oxfordjournals.org/content/51/1/9.full.pdf+html
Evidence for Multiple-Antibiotic Resistance in Campylobacter jejuni Not Mediated by CmeB or CmeF Lilian Pumbwe,1 Luke P. Randall,2 Martin J. Woodward,2 and Laura J. V. Piddock http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1068584/pdf/0475-04.pdf
Interaction of CmeABC and CmeDEF in conferring antimicrobial resistance and maintaining cell viability in Campylobacter jejuni Masato Akiba†, Jun Lin‡, Yi-Wen Barton and Qijing Zhang http://jac.oxfordjournals.org/content/57/1/52.full.pdf
