Bioinformatics Interview Question:

Does multidrug resistance (MDR) arise by activation of stable genes encoding drug efflux pumps or by mutations of genes encoding other types of transporters in bacterial pathogens?

Submitted by: Administrator

MDR efflux pumps began causing clinical problems relatively recently, in parallel with the extensive use of antibiotics in medicine and as supplements in animal feeds. However, our analyses indicate that these MDR efflux pumps did not arise through recent mutations in genes encoding transporters that changed their substrate specificities.
Instead, such MDR pumps are encoded within the genomes of virtually all microorganisms, so these genes are present and thus need only to be activated to become problematic. Moreover, lateral transfer of genes among bacteria has occurred frequently, particularly for plasmid-encoded systems, suggesting that such genes can be acquired fairly readily even if they are not initially present. Finally, although mutations that enable transporters to act on different types of substrate are rare, experiments and phylogenetic analyses indicate that simple point mutations can readily narrow or broaden a particular transporter's specificity toward a single class of compounds. These findings provide clues for developing strategies to control MDR among bacterial pathogens.
Submitted by: