Antibiotic‐mediated recombination: ciprofloxacin stimulates SOS‐independent recombination of divergent sequences in <i>Escherichia coli</i>

López, Elena; Elez, Marina; Matić, Ivan; Blázquez, Jesús

doi:10.1111/j.1365-2958.2007.05642.x

Cited by 124 publications

(105 citation statements)

References 66 publications

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“…Furthermore, in the clinical E. coli isolates that were rendered FQ resistant through selection in the presence of ciprofloxacin, no loss of PAIs occurred (20,31). Moreover, E. coli 536 shows a loss of PAIs that appears without gyra mutation and without any antibiotics in the medium (32), indicating that their instability could be exacerbated by several stimuli (32), of which the presence of quinolone is just one (29).…”

Section: Discussionmentioning

confidence: 99%

Virulence Factors in Urinary Escherichia coli Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance

Piatti¹,

et al. 2008

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Quinolone-and fluoroquinolone-resistant Escherichia coli strains harbor fewer virulence factors than susceptible strains. The reasons underlying this correlation are incompletely understood. We investigated the phylogenetic background, the presence of the papC, hlyA, and cnf1 (pathogenicity island II J96 -associated), fimA, iss, and iutA genes, and the presence of type 1 fimbriae, P fimbriae, and hemolysin in 243 urinary E. coli isolates resistant only to quinolones (8%), resistant to both quinolones and fluoroquinolones (51%), or susceptible to both drugs (41%). Group B2 accounted for 56% of the isolates, showing a significantly higher prevalence among fluoroquinolone-susceptible strains than among resistant strains (65% versus 50% [P ‫؍‬ 0.03]). hly and cnf1 were significantly more associated with susceptibility (P < 0.001) and with group B2 (P < 0.001 for group B2 versus groups A and D). However, within group B2, fluoroquinolone-resistant strains showed lower prevalences of papC, hlyA, and cnf1 than their susceptible counterparts (P < 0.001). In contrast, the incidence of iutA appeared higher for refractory isolates, including group B2, than for susceptible isolates (P < 0.001). Only in group B2 did fluoroquinolone-resistant strains reveal a lesser ability to agglutinate Saccharomyces cerevisiae (7%) than quinolone-resistant (87%) and susceptible (80%) isolates, despite uniform possession of fimA genes. No similar contrast emerged for expression of hemolysin and P fimbriae. Mutations conferring quinolone and fluoroquinolone resistance may thus require a particular genetic background, not strictly correlated with phylogenetic groups. More interestingly, the mutational event itself can affect the expression of type 1 fimbriae, at least in the prevalent and complex B2 strains.Urinary tract infections (UTIs) in humans are the most frequent bacterial disease, affecting both inpatients and outpatients. Especially the uncomplicated cases are mainly due to extraintestinal pathogenic Escherichia coli (ExPEC) (39). In recent years, management of UTIs has become increasingly problematic due to the emergence of resistance to first-line antibiotics among the causative bacteria, particularly among uropathogenic E. coli (UPEC) strains. This phenomenon involves quinolones (Q) and fluoroquinolones (FQ) (25), drugs of paramount importance in the treatment of several other infectious diseases. Indeed, the renal excretion of these molecules and the availability of oral and parenteral formulations have allowed them to compete with aminoglycosides and betalactams in the therapy of complicated UTIs, especially in the hospital setting. Their appropriate spectrum and good tolerability have also led to increased empirical adoption in uncomplicated infections, although their usage for these conditions in outpatients is still under debate.In E. coli, as in other gram-negative bacteria, DNA gyrase, which codifies type II DNA topoisomerases, is the main target of Q and FQ, and mutation in gyrA is the most common way to acquire resistance....

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Section: Discussionmentioning

confidence: 99%

Virulence Factors in Urinary Escherichia coli Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance

Piatti¹,

et al. 2008

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“…The fluoroquinolone antibiotic ciprofloxacin, an inhibitor of type II DNA topoisomerases, stimulates intrachromosomal and conjugational recombination of DNA sequences, including resistance genes, in E. coli (Ló pez et al, 2007). This stimulation also occurs in a hyper-recombinogenic mismatch repair mutS mutant.…”

Section: Using Insertional Inactivation Of the Muts Gene Inmentioning

confidence: 99%

Bacterial hypermutation: clinical implications

Jolivet‐Gougeon

Kovács

Gall‐David

et al. 2011

Journal of Medical Microbiology

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Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research. IntroductionEradication of infectious diseases is constantly challenged by micro-organisms that develop new survival strategies. Previous studies suggest that mutational events play a predominant role in bacterial adaptation and confer a selective advantage (Chou et al., 2009;Cooper, 2007). Early experiments aimed at detecting mutators used mutagenized laboratory strains of bacteria, sometimes coupled with different selection strategies. LeClerc et al. (1996) reported high mutation frequency among Escherichia coli and Salmonella pathogens, challenging the theory that mutators were rare among bacterial populations. Taken together, these findings demonstrated that natural populations could respond to environmental selection in two ways, i.e. by enhanced mutation frequencies and by recombination. Transient mutator status, which involves reversion or recombination within the mutator alleles or depletion of the methyl-directed mismatch repair (MMR) system proteins, allows the organism to temporarily benefit from the elevated mutation frequency for adaptation while reducing the risk of accumulating deleterious mutations. Using a mathematical model, Rosche & Foster (1999) showed that transient hypermutators play a role in adaptive mutation in E. coli. Molecular mechanisms of hypermutationProteins involved in the DNA mismatch repair pathway help replace nucleotides introduced erroneously into the replicated DNA and also hinder recombination between non-identical DNA sequences. Deficiencies in any of the DNA mismatch repair pathway mechanisms can lead to a hypermutator phenotype. DNA repairSiegel & Bryson (1967) discovered the mutS gene in an azaserine-resistant derivative of E. coli that had a mutator phenotype and carried a deletion in the mutS gene. The majority of naturally occurring strong mutators have defects in the MMR system; the mutations are mainly in mutS (Oliver et al., 2002), but deletions in genes encoding beta-clamp proteins and in mutH, mutL and mutU (uvrD) have also been described (Fig. 1). Inactivation of basal excision repair genes, e.g. mutY, mutM, ...

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“…Under sustained exposure to norfloxacin, mutation rates revealed by reporter constructs can be elevated 2-9 times (18,23). Norfloxacin is also thought to elevate intracellular reactive oxygen species (ROS) levels (24,25), which may further increase the rate of genomic mutation and the subsequent rate of acquisition of multidrug resistance (23,26).…”

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

Long

Miller

Strauss

et al. 2016

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

177

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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Antibiotic‐mediated recombination: ciprofloxacin stimulates SOS‐independent recombination of divergent sequences in Escherichia coli

Cited by 124 publications

References 66 publications

Virulence Factors in Urinary Escherichia coli Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance

Virulence Factors in Urinary Escherichia coli Strains: Phylogenetic Background and Quinolone and Fluoroquinolone Resistance

Bacterial hypermutation: clinical implications

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

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