Antimicrobials as promoters of genetic variation

Blázquez, Jesús; Couce, Alejandro; Rodríguez-Beltrán, Jerónimo; Rodríguez‐Rojas, Alexandro

doi:10.1016/j.mib.2012.07.007

Cited by 164 publications

(118 citation statements)

References 93 publications

(59 reference statements)

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“…Moreover, we observed that the proportion of gene cassette variants in the hospital effluent was very low but increased along the wastewater flow. Antibiotics might indeed enrich the more efficient adaptive genes (Blázquez et al, 2012;Baquero et al, 2013).…”

Section: Gene Cassette Diversity and Shufflingmentioning

confidence: 99%

Quantitative and qualitative impact of hospital effluent on dissemination of the integron pool

et al. 2013

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There is increasing evidence that human activity, and especially the resulting effluent, has a major role in the dissemination of bacterial antibiotic-resistance determinants in the environment. Hospitals are the major antibiotic consumers and thus facilitate the spread of antibiotic resistance. Questions are increasingly being raised about the management of hospital effluents, but their involvement in antibiotic-resistance dissemination has never been assessed. Integrons are a paradigm of genetic transfer between the environmental resistome and both commensal and pathogenic bacteria. In order to assess the impact of hospital activities on antibiotic-resistance dissemination in the environment, we monitored integrons and their gene cassettes in hospital effluents, and their release in the environment. We found that bacterial communities present in a hospital effluent contained a high proportion of integrons. In terms of both their gene cassette diversity and gene cassette arrays, the urban effluent and municipal wastewater treatment plant (WWTP) influent were most similar, whereas the hospital effluent and recirculation sludge exhibited very specific patterns. We found that anthropogenic activities led to the release of abundant integrons and antibiotic-resistance gene cassettes, but we observed no specific impact of hospital activities on the receiving environment. Furthermore, although the WWTP did not reduce the normalized integron copy number, it reduced the diversity of gene cassette arrays contained in the raw wastewater, underlining the effect of the biological treatment on the anthropogenic integron pool arriving at the WWTP.

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Section: Gene Cassette Diversity and Shufflingmentioning

confidence: 99%

Quantitative and qualitative impact of hospital effluent on dissemination of the integron pool

et al. 2013

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“…Although mutator strains can have longterm disadvantages, owing to the accumulation of harmful mutations (10), in the face of strong selective challenges, the short-term benefits of resistance mutations can take precedence, leading to antibiotic treatment failure for infectious diseases (11). However, there have been only a few empirical comparisons of resistance evolution in mutator vs. nonmutator lines under long-term sublethal antibiotic exposure (12,13).…”

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confidence: 99%

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Long

Miller

Strauss

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

178

143

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Although it is well known that microbial populations can respond adaptively to challenges from antibiotics, empirical difficulties in distinguishing the roles of de novo mutation and natural selection have left several issues unresolved. Here, we explore the mutational properties of Escherichia coli exposed to long-term sublethal levels of the antibiotic norfloxacin, using a mutation accumulation design combined with whole-genome sequencing of replicate lines. The genome-wide mutation rate significantly increases with norfloxacin concentration. This response is associated with enhanced expression of error-prone DNA polymerases and may also involve indirect effects of norfloxacin on DNA mismatch and oxidative-damage repair. Moreover, we find that acquisition of antibiotic resistance can be enhanced solely by accelerated mutagenesis, i.e., without direct involvement of selection. Our results suggest that antibiotics may generally enhance the mutation rates of target cells, thereby accelerating the rate of adaptation not only to the antibiotic itself but to additional challenges faced by invasive pathogens.antibiotic resistance | mutation rate | resistance evolution | DNA repair | low-fidelity polymerases

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“…For instance, endogenous oxidative stress in biofilms of P. aeruginosa has been shown to promote mutagenesis via the mutagenic repair of double-strand breaks in DNA (5). In addition, it is becoming clear that low-dose antibiotic treatment itself promotes the development of mutational resistance (6,7). Conditions of low antibiotic levels might arise due to inappropriate dosages but also due to different distributions depending on the body compartments (6).…”

mentioning

confidence: 99%

“…Antibiotics, and especially fluoroquinolones, have been shown to promote genetic variation in planktonic cells by means of different pathways involving oxidative stress, the SOS response, or acting directly on DNA (7).…”

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confidence: 99%

Real-Time Monitoring of nfxB Mutant Occurrence and Dynamics in Pseudomonas aeruginosa Biofilm Exposed to Subinhibitory Concentrations of Ciprofloxacin

Zaborskytė

Andersen

Kragh

et al. 2017

Antimicrob Agents Chemother

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Biofilm infections caused by Pseudomonas aeruginosa are frequently treated with ciprofloxacin (CIP); however, resistance rapidly develops. One of the primary resistance mechanisms is the overexpression of the MexCD-OprJ pump due to a mutation in nfxB, encoding the transcriptional repressor of this pump. The aim of this study was to investigate the effect of subinhibitory concentrations of CIP on the occurrence of nfxB mutants in the wild-type PAO1 flow cell biofilm model. For this purpose, we constructed fluorescent reporter strains (PAO1 background) with an mCherry tag for constitutive red fluorescence and chromosomal transcriptional fusion between the P mexCD promoter and gfp leading to green fluorescence upon mutation of nfxB. We observed a rapid development of nfxB mutants by live confocal laser scanning microscopy (CLSM) imaging of the flow cell biofilm (reaching 80 to 90% of the whole population) when treated with 1/10 minimal biofilm inhibitory concentration of CIP for 24 h and 96 h. Based on the observed developmental stages, we propose that nfxB mutants emerged de novo in the biofilm during CIP treatment from filamentous cells, which might have arisen due to the stress responses induced by CIP. Identical nfxB mutations were found in fluorescent colonies from the same flow cell biofilm, especially in 24-h biofilms, suggesting selection and clonal expansion of the mutants during biofilm growth. Our findings point at the significant role of high-enough antibiotic dosages or appropriate combination therapy to avoid the emergence of resistant mutants in biofilms.

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Antimicrobials as promoters of genetic variation

Cited by 164 publications

References 93 publications

Quantitative and qualitative impact of hospital effluent on dissemination of the integron pool

Quantitative and qualitative impact of hospital effluent on dissemination of the integron pool

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Real-Time Monitoring of nfxB Mutant Occurrence and Dynamics in Pseudomonas aeruginosa Biofilm Exposed to Subinhibitory Concentrations of Ciprofloxacin

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