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The Effects of Sub-inhibitory Antibiotic Concentrations on Pseudomonas aeruginosa : Reduced Susceptibility Due to Mutations.

التفاصيل البيبلوغرافية
العنوان: The Effects of Sub-inhibitory Antibiotic Concentrations on Pseudomonas aeruginosa : Reduced Susceptibility Due to Mutations.
المؤلفون: Ramsay KA; Department of Biochemistry, University of Otago, Dunedin, New Zealand., McTavish SM; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Wardell SJT; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Lamont IL; Department of Biochemistry, University of Otago, Dunedin, New Zealand.
المصدر: Frontiers in microbiology [Front Microbiol] 2021 Dec 20; Vol. 12, pp. 789550. Date of Electronic Publication: 2021 Dec 20 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101548977 Publication Model: eCollection Cited Medium: Print ISSN: 1664-302X (Print) Linking ISSN: 1664302X NLM ISO Abbreviation: Front Microbiol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Pseudomonas aeruginosa chronically infects in the lungs of people with cystic fibrosis and other forms of lung disease. Infections are treated with antibiotics, but over time, the bacteria acquire mutations that reduce their antibiotic susceptibility. The effects of inhibitory amounts of antibiotics in selecting for antibiotic-resistant mutants have been well studied. However, the concentrations of antibiotics that reach infecting bacteria can be sub-inhibitory and but may nonetheless promote emergence of antibiotic-resistant bacteria. Therefore, the aim of this research was to investigate the effects of sub-inhibitory concentrations of antibiotics on the antibiotic susceptibility of P. aeruginosa . Two P. aeruginosa reference strains, PAO1 and PA14, and six isolates from individuals with cystic fibrosis were studied. The bacteria were passaged in the presence of antibiotics (ceftazidime, ciprofloxacin, meropenem or tobramycin) at sub-inhibitory amounts. Fifteen populations of bacteria (up to five per strain) were exposed to each of the four antibiotics. Antibiotic susceptibility was determined following 10 passages on agar supplemented with antibiotic and compared with susceptibility prior to antibiotic exposure. Antibiotic exposure resulted in susceptibility being significantly (>2-fold) reduced for 13 of the 60 populations. Seven samples had reduced susceptibility to ciprofloxacin, three to tobramycin, two to ceftazidime and one to meropenem. Whole-genome sequencing revealed the mutations arising following antibiotic exposure. Mutants with reduced antibiotic susceptibility had mutations in genes known to affect antibiotic resistance, including regulators of efflux pumps ( mexR , mexS , mexZ and nalC ) and the fusA1 gene that is associated with aminoglycoside resistance. Genes not previously associated with resistance, including gacS , sigX and crfX and two genes with no known function, were also mutated in some isolates with reduced antibiotic susceptibility. Our results show that exposure to sub-inhibitory amounts of antibiotics can select for mutations that reduce the susceptibility of P. aeruginosa to antibiotics and that the profile of mutations is different from that arising during selection with inhibitory antibiotic concentrations. It is likely that exposure to sub-inhibitory amounts of antibiotics during infection contributes to P. aeruginosa becoming antibiotic-resistant.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Ramsay, McTavish, Wardell and Lamont.)
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فهرسة مساهمة: Keywords: Pseudomonas aeruginosa; antibiotic resistance; cystic fibrosis; genetic mutations; resistance mechanisms; sub-inhibitory concentration; sub-lethal concentration
تواريخ الأحداث: Date Created: 20220106 Latest Revision: 20231108
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8721600
DOI: 10.3389/fmicb.2021.789550
PMID: 34987489
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-302X
DOI:10.3389/fmicb.2021.789550