Question

Why is MRSA resistant to beta lactams?

Answer 1

They have the mecA gene. The gene encodes the protein PBP2A (penicillin binding protein 2A). PBP2A has a low affinity for beta-lactam antibiotics

Explanation:

Enzymes like D,D-transpeptidase are PBPs or penicillin-binding protein. However, a variant of PBP called PBP2A has a low affinity for beta-lactam antibiotics such as methicillin and penicillin.

This protein is enconded by the mecA gene. The origin of mecA gene is unknown but it was acquired by MSSA (meticilin-susceptible staphylococcus aureus) through horizontal gene transfer to becomeMRSA (meticilin-resistant staphylococcus aureus) But it is probable that the ancestral gene comes from Staphylococcus sciuri.

There are a few conformational changes of the transpeptide domain of PBP2a compared to normal PBP as can be observed in figure below. The distorted conformation/position causes lower affinity of beta-lactam to PBP2a

[1] The Basis for Resistance to
-Lactam Antibiotics by Penicillin binding Protein 2a of Methicillin-resistant Staphylococcus aureus, Cosimo Fuda, Maxim Suvorov, Sergei B. Vakulenko, and Shahriar Mobashery
http://www.jbc.org/content/279/39/40802.full.pdf+html
[2] Antimicrobial resistance: the example of Staphylococcus aureus Franklin D. Lowy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC154455/pdf/JCI0318535.pdf
[3] https://www.quora.com/How-did-certain-bacteria-become-resistant-to-certain-antibiotics/answer/Stuart-Rawson
[4] Structural Basis of β-Lactam Resistance in Methicillin-Resistant Strains of “Superbug” Revealed D. Lim and N.C.J. Strynadka https://www.bnl.gov/isd/documents/26322/sh_life_sci_3.pdf