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Molecular Evolution of the Pseudomonas aeruginosa DNA Gyrase gyrA Gene

Authors :
Mitsuru Sada
Hirokazu Kimura
Norika Nagasawa
Mao Akagawa
Kaori Okayama
Tatsuya Shirai
Soyoka Sunagawa
Ryusuke Kimura
Takeshi Saraya
Haruyuki Ishii
Daisuke Kurai
Takeshi Tsugawa
Atsuyoshi Nishina
Haruyoshi Tomita
Mitsuaki Okodo
Shinichiro Hirai
Akihide Ryo
Taisei Ishioka
Koichi Murakami
Source :
Microorganisms; Volume 10; Issue 8; Pages: 1660
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

DNA gyrase plays important roles in genome replication in various bacteria, including Pseudomonasaeruginosa. The gyrA gene encodes the gyrase subunit A protein (GyrA). Mutations in GyrA are associated with resistance to quinolone-based antibiotics. We performed a detailed molecular evolutionary analyses of the gyrA gene and associated resistance to the quinolone drug, ciprofloxacin, using bioinformatics techniques. We produced an evolutionary phylogenetic tree using the Bayesian Markov Chain Monte Carlo (MCMC) method. This tree indicated that a common ancestor of the gene was present over 760 years ago, and the offspring formed multiple clusters. Quinolone drug-resistance-associated amino-acid substitutions in GyrA, including T83I and D87N, emerged after the drug was used clinically. These substitutions appeared to be positive selection sites. The molecular affinity between ciprofloxacin and the GyrA protein containing T83I and/or D87N decreased significantly compared to that between the drug and GyrA protein, with no substitutions. The rate of evolution of the gene before quinolone drugs were first used in the clinic, in 1962, was significantly lower than that after the drug was used. These results suggest that the gyrA gene evolved to permit the bacterium to overcome quinolone treatment.

Details

ISSN :
20762607
Volume :
10
Database :
OpenAIRE
Journal :
Microorganisms
Accession number :
edsair.doi.dedup.....a59e5e4be67fefa247703f7aafa55c9d
Full Text :
https://doi.org/10.3390/microorganisms10081660