Susceptibility of Mycobacterium tuberculosis Cytochrome <i>bd</i> Oxidase Mutants to Compounds Targeting the Terminal Respiratory Oxidase, Cytochrome <i>c</i>

Abstract

We deleted subunits I (<i>cydA</i>) and II (<i>cydB</i>) of the <i>Mycobacterium tuberculosis</i> cytochrome <i>bd</i> menaquinol oxidase. The resulting Δ<i>cydA</i> and Δ<i>cydAB</i> mutants were hypersusceptible to compounds targeting the mycobacterial <i>bc</i>₁ menaquinol-cytochrome <i>c</i> oxidoreductase and exhibited bioenergetic profiles indistinguishable from strains deficient in the ABC-type transporter, CydDC, predicted to be essential for cytochrome <i>bd</i> assembly. These results confirm CydAB and CydDC as potential targets for drugs aimed at inhibiting a terminal respiratory oxidase implicated in pathogenesis.