In 474 genome sequenced Pseudomonas aeruginosa isolates from 34 cystic fibrosis (CF) patients, 40% of these harbor mutations in the mexZ gene encoding a negative regulator of the MexXY-OprM efflux pump associated with aminoglycoside and fluoroquinolone resistance. Surprisingly, resistance to aminoglycosides and fluoroquinolones of mexZ mutants was far below the breakpoint of clinical resistance. However, the fitness increase of the mutant bacteria in presence of the relevant antibiotics, as demonstrated in competition experiments between mutant and ancestor bacteria, showed that 1) very small phenotypic changes cause significant fitness increase with severe adaptive consequences, and 2) standardized phenotypic tests fail to detect such low-level variations. The frequent appearance of P. aeruginosa mexZ mutants in CF patients is directly connected to the intense use of the target antibiotics, and low-level antibiotic resistance, if left unnoticed, can result in accumulation of additional genetic changes leading to high-level resistance.
Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts / J. Frimodt-Moller, E. Rossi, J.A.J. Haagensen, M. Falcone, S. Molin, H.K. Johansen. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018 Aug), pp. 12512.1-12512.13.
|Titolo:||Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts|
ROSSI, ELIO (Secondo)
|Parole Chiave:||Adaptation, Physiological; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Cystic Fibrosis; Fluoroquinolones; Genetic Fitness; Humans; Phenotype; Pseudomonas Infections; Pseudomonas aeruginosa; Sequence Analysis, RNA; Whole Genome Sequencing; Drug Resistance, Microbial; Mutation|
|Settore Scientifico Disciplinare:||Settore BIO/19 - Microbiologia Generale|
Settore BIO/11 - Biologia Molecolare
Settore BIO/18 - Genetica
Settore MED/07 - Microbiologia e Microbiologia Clinica
|Data di pubblicazione:||ago-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41598-018-30972-y|
|Appare nelle tipologie:||01 - Articolo su periodico|