Interplay between plasmid-mediated and chromosomal-mediated fluoroquinolone resistance and bacterial fitness in Escherichia coli

Machuca, Jesús; Briales, Alejandra; Labrador, G.; Díaz-de-Alba, Paula; López-Rojas, Rafael; Docobo-Pérez, Fernando; Martínez-Martínez, Luis; Rodríguez-Baño, Jesús; Pachón, M. E.; Pascual, Álvaro; Rodríguez-Martínez, José Manuel

doi:10.1093/jac/dku308

Cited by 77 publications

(63 citation statements)

References 55 publications

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“…Escherichia coli can survive for a long period outside the intestinal tract of mammals (Sjögren, 1995). In addition, mutations conferring resistance to quinolones are not always associated with a fitness cost for the bacteria; instead, fitness may actually increase (de Lastours et al, 2014;Machuca et al, 2014). It is therefore logical to assume that QREC may be introduced to, and established in, naïve farm animals through purchase of animals carrying resistant bacteria or through contaminated farm equipment.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows

Duse

Waller

Emanuelson

et al. 2015

Journal of Dairy Science

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Quinolone resistance may emerge in gut bacteria (e.g., in Escherichia coli) of animals. Such bacteria could cause infections in the animal itself or be transmitted to humans via the food chain. Quinolone resistance is also observed in fecal E. coli of healthy dairy cattle, but the prevalence varies between farms, not solely as a result of varying degree of fluoroquinolone exposure. The objective of this study was to identify risk factors for the fecal shedding of quinolone-resistant E. coli (QREC) from dairy calves and postpartum cows. Rectal swabs from 15 preweaned calves and 5 postpartum cows per farm were collected on 23 Swedish dairy farms to determine the prevalence of QREC. Risk factors for the shedding of QREC were investigated using multivariable statistical models. Quinolone-resistant E. coli were found on all but one farm. Factors associated with QREC shedding by calves were being younger than 18 d, being fed milk from cows treated with antimicrobials, recent use of fluoroquinolones in the herd, carriage of QREC by postpartum cows, and using the calving area never or rarely as a sick pen compared with often. Factors associated with QREC shedding by cows were calving in group pens or freestalls compared with single pens or tiestalls, purchasing cattle, sharing animal transports with other farmers, and poor farm hygiene. Proper biosecurity and improved hygiene, as well as minimizing fluoroquinolone exposure and waste milk feeding, may be important factors to reduce the burden of QREC on dairy farms.

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Section: Discussionmentioning

confidence: 99%

Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows

Duse

Waller

Emanuelson

et al. 2015

Journal of Dairy Science

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“…Wild-type E. coli ATCC 25922 and nine different isogenic strains carrying combinations of the most prevalent chromosomal mutations (⌬marR, gyrA-S83L, gyrA-D87N, and parC-S80R) were used. Isogenic strains were those constructed previously by Machuca et al (23). Moreover, six uropathogenic E. coli (UPEC) strains with well-characterized LLQR mutations that had been isolated from patients in the University Hospital Marques de Valdecilla and University Hospital Virgen Macarena during 2009 were studied (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli

Martín-Gutiérrez

Rodríguez-Beltrán

Rodríguez-Martínez

et al. 2016

Antimicrob Agents Chemother

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Escherichia coli isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in E. coli. However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (⌬marR, gyrA-S83L, gyrA-D87N, and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR E. coli variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in E. coli. Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR E. coli in UTIs.C iprofloxacin (CIP) is one of the agents commonly utilized for treatment of urinary tract infections (UTIs) (1-3). It is used as an appropriate therapy in patients with UTI not requiring hospitalization in areas where the prevalence of resistance is under 10%. In addition, it is considered an effective treatment in the prevention of UTI in kidney transplant recipients (4, 5). However, during recent years a clear increase in resistance to fluoroquinolones (FQ) has been described worldwide (6, 7).The predominant causative agent of community-acquired UTI, Escherichia coli, acquires resistance mainly through chromosomal mutations in the genes encoding subunits of the DNA gyrase (gyrA and gyrB genes) and topoisomerase IV (parC and parE genes) or in regulatory genes affecting permeability or efflux (8). Some of these mutations lead to generation of low-level-quinolone-resistant (LLQR) E. coli mutants, with a CIP MIC that is higher than the epidemiological cutoff value but still below the resistance breakpoint for most FQs. A high (from 17% to 39%, depending on the study) prevalence of LLQR E. coli in UTIs has been previously described (8,9). However, the causes of this prevalence are unclear, as the high CIP levels found in the bladder after treatment should be sufficient to eradicate any susceptible bacteria.It has been stated that small increases in MIC values produced by LLQR mutations have a profound impact on t...

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“…Additionally, plasmid-mediated quinolone resistance (PMQR) mechanisms (Qnr proteins that protect the quinolone targets; the acetylation of ciprofloxacin and norfloxacin by Aac(6′)-Ib-cr; and the plasmid-mediated efflux pumps, QepA and OqxAB) have also been described and are epidemiologically relevant (Rodríguez-Martínez et al, 2011, 2016b; Jacoby et al, 2014). All these determinants (chromosomal or plasmid mediated) on their own confer low-level quinolone resistance (LLQR), and multiple mechanisms must be combined to achieve clinical levels of resistance (Morgan-Linnell and Zechiedrich, 2007; Morgan-Linnell et al, 2009; Briales et al, 2011; Machuca et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli

et al. 2017

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Bactericidal activity of quinolones has been related to a combination of DNA fragmentation, reactive oxygen species (ROS) production and programmed cell death (PCD) systems. The underlying molecular systems responsible for reducing bactericidal effect during antimicrobial therapy in low-level quinolone resistance (LLQR) phenotypes need to be clarified. To do this and also define possible new antimicrobial targets, the transcriptome profile of isogenic Escherichia coli harboring quinolone resistance mechanisms in the presence of a clinical relevant concentration of ciprofloxacin was evaluated. A marked differential response to ciprofloxacin of either up- or downregulation was observed in LLQR strains. Multiple genes implicated in ROS modulation (related to the TCA cycle, aerobic respiration and detoxification systems) were upregulated (sdhC up to 63.5-fold) in mutants with LLQR. SOS system components were downregulated (recA up to 30.7-fold). yihE, a protective kinase coding for PCD, was also upregulated (up to 5.2-fold). SdhC inhibition sensitized LLQR phenotypes (up to ΔLog = 2.3 after 24 h). At clinically relevant concentrations of ciprofloxacin, gene expression patterns in critical systems to bacterial survival and mutant development were significantly modified in LLQR phenotypes. Chemical inhibition of SdhC (succinate dehydrogenase) validated modulation of ROS as an interesting target for bacterial sensitization.

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Interplay between plasmid-mediated and chromosomal-mediated fluoroquinolone resistance and bacterial fitness in Escherichia coli

Cited by 77 publications

References 55 publications

Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows

Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows

Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli

Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli

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