In Vitro Assessment of the Fitness of Resistant M. tuberculosis Bacteria by Competition Assay

Bacteria become resistant by a number of different mechanisms, and these include mutation in chromosomal genes (1 ), acquisition of plasmids (2 ), insertion of bacteriophage, transposon or insertion sequence DNA (3 -5 ), or gene mosaicism (6 ). There is a dogma that bacteria that become resistant pay a significant physiological price and that if antimicrobial prescribing is controlled it will result in the eradication of resistant organisms. There are only very few studies that investigate the physiology of resistance acquisition and these do show that a physiological price is paid for this change (7 , 8 ). Once an organism acquires resistance through mutation, acquisition of resistance genes via plasmids, transposons and bacteriophages the initial physiological defect is compensated by the antibiotic selective pressure, which balances the physiological deficit imposed by the resistant mutation or additional DNA (8 , 9 ).