Journal
ANTIBIOTICS-BASEL
Volume 10, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/antibiotics10060658
Keywords
Pseudomonas aeruginosa; MexXY multidrug efflux system; pyoverdine production
Categories
Funding
- JSPS KAKENHI [19K07547]
- Research Program of Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials in Network Joint Research Center for Materials and Devices
- Grants-in-Aid for Scientific Research [19K07547] Funding Source: KAKEN
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The study found that MexXY overexpression and deficiency in multidrug-resistant Pseudomonas aeruginosa can impact pyoverdine production, with MexXY deficiency leading to increased pyoverdine production. MexXY-deficient mutants may be more susceptible to iron deficiency, while high-risk clones are usually MexXY overproducers but defective pyoverdine producers.
Multidrug-resistant Pseudomonas aeruginosa poses a serious problem due to hospital- and healthcare-associated infections. A major drug resistance mechanism of P. aeruginosa involves active efflux via resistance nodulation cell division (RND)-type multidrug efflux pumps of which MexXY is increasingly recognized as a primary determinant of aminoglycoside resistance in P. aeruginosa. MexXY overexpression is often observed in drug-resistant P. aeruginosa clinical isolates. MexXY deficiency increased pyoverdine production in all four P. aeruginosa strains we tested. MexXY-overproducing multidrug-resistant P. aeruginosa PA7 exhibited the greatest effect among the strains. Complementation with a MexXY-expressing plasmid restored low-level pyoverdine production in a MexXY-deficient P. aeruginosa mutant from PA7, indicating that MexXY expression decreases pyoverdine production. Because P. aeruginosa produces pyoverdine to acquire iron, MexXY-deficient mutants might be more susceptible to iron deficiency than MexXY-producing strains or might require extra iron. High-risk clones of multidrug-resistant P. aeruginosa reportedly tend to be MexXY overproducers but defective pyoverdine producers. This study suggests that P. aeruginosa reduces production of a virulence factor after acquiring a drug resistance factor.
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