Influence of the TonB Energy-Coupling Protein on Efflux-Mediated Multidrug Resistance inPseudomonas aeruginosa

• DOI: 10.1128/aac.42.9.2225
• Publication Date: 2018-10-09T00:33:24Z
• Authors: Qixun Zhao; Xian-Zhi Li; Anita Mistry; Ramakrishnan Srik...; Li Zhang; Olga Lomovskaya; Keith Poole
• Keywords: 0301 basic medicine; 03 medical and health sciences; Bacterial Proteins; Iron; Operon; Pseudomonas aeruginosa; Membrane Proteins; Drug Resistance, Multiple; Anti-Bacterial Agents

ABSTRACTTonB couples the energized state of the cytoplasmic membrane to the operation of outer membrane receptors responsible for Fe(III) siderophore uptake across the outer membrane of gram-negative bacteria. AtonBmutant ofPseudomonas aeruginosadeficient in iron siderophore uptake was shown in the present study to be hypersusceptible to a wide variety of antibiotics, reminiscent of the phenotype of mutants defective in themexAB-oprMantibiotic efflux operon. This was not related to influences of atonBmutation on the iron status of the cell, and indeed, intrinsic antibiotic susceptibility andmexAB-oprMexpression were unaffected by iron levels in the growth medium. The presence oftonBon a multicopy plasmid increased the level of resistance of a MexAB-OprM+strain but not that of a MexAB-OprM−strain to a variety of antimicrobial agents.mexAB-oprMexpression was not, however, altered in atonBdeletion mutant, indicating that any influence of TonB on MexAB-OprM-mediated multidrug resistance was at the level of pump activity. Consistent with this, drug accumulation assays revealed that thetonBdeletion mutant exhibited decreased levels of drug efflux. Still, the multidrug resistance of analBstrain was not wholly abrogated by atonBmutation, indicating that it is likely not an essential component of the efflux apparatus. Similarly, elimination oftonBfrom annfxBstrain only partially compromised MexCD-OprJ-mediated multidrug resistance. Intriguingly, the drug susceptibility of amexAB-oprMdeletion strain was increased following deletion oftonB, suggesting that TonB may also influence antibiotic resistance mediated by determinants other than MexAB-OprM (and MexCD-OprJ). Thus, TonB plays an important role in both intrinsic and acquired antibiotic resistance inP. aeruginosa.