Genomic and phenotypic characterisation of fluoroquinolone resistance mechanisms in Enterobacteriaceae in Durban, South Africa

Sekyere, John Osei; Amoako, Daniel G.

doi:10.1371/journal.pone.0178888

Cited by 57 publications

(69 citation statements)

References 27 publications

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“…Only three observational studies reported on the presence of all currently known resistance determinants. 33,97,98 Since mutations in both acrR and marR genes were shown to result in no to low fold changes in ciprofloxacin MIC, we added five observational studies that fulfilled all inclusion and exclusion criteria except testing for the presence of mutations in acrR and marR genes, in a secondary analysis. Thus, eight observational studies published between 2012 and 2018 were included, contributing data on a total of 238 strains (Table S2).…”

Section: Resultsmentioning

confidence: 99%

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Remondini

Pasquini

et al. 2018

Preprint

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SynopsisIntroductionCiprofloxacin resistance in Escherichia coli is widespread and adds to the burden of E. coli infections. Reviews assessing the genetic basis of ciprofloxacin resistance have mostly been qualitative. However, to allow for the prediction of a resistance phenotype of clinical relevance based on genotypic characteristics, it is essential to quantify the contribution of prevalent genotypic determinants to resistance. We carried out a systematic review to assess the relative contribution of currently known genomic resistance determinants to the minimum inhibitory concentration (MIC) of ciprofloxacin in E. coli.MethodsPubMed and Web of Science were searched for English language studies that assessed both ciprofloxacin MIC and the presence or introduction of genetic determinants of ciprofloxacin resistance in E. coli. We included experimental and observational studies without time restrictions. Medians and ranges of MIC fold changes were calculated for each resistance determinant and for combinations of determinants.ResultsWe included 66 studies, describing 604 E. coli isolates that carried at least one genetic resistance determinant. Genes coding for targets of ciprofloxacin (gyrA and parC) are strongest contributors to ciprofloxacin resistance, with median MIC fold increases ranging from 24 (range 4-133) for single Ser83Leu (gyrA) mutants to 1533 (range 256-8533) for triple Ser83Leu, Asp87Asn/Gly (gyrA) and Ser80Ile/Arg (parC) mutants. Other resistance mechanisms, including efflux, physical blocking or enzymatic modification, conferred smaller increases in ciprofloxacin MIC (median MIC fold increases typically around 15, range 1-125). However, the (combined) presence of these other resistance mechanisms further increases resistance with median MIC fold increases of up to 4000, and even in the absence of gyrA and parC mutations up to 250.ConclusionThis report provides a comprehensive and quantitative overview of the contribution of different genomic determinants to ciprofloxacin resistance in E. coli. Additionally, the data demonstrate the complexity of resistance phenotype prediction from genomic data and could serve as a reference point for studies aiming to address ciprofloxacin resistance prediction using genomics, in E. coli.

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Section: Resultsmentioning

confidence: 99%

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Remondini

Pasquini

et al. 2018

Preprint

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“…Fluoroquinolone resistance mechanisms were further investigated by determining mutations in DNA gyrase ( gyrA ) and topoisomerase IV ( parC ) using fluoroquinolone‐susceptible P. rettgeri DSM 1131 (accession no. ACCI00000000) as the reference/wild‐type strain to call single‐nucleotide polymorphisms (SNPs) with tBLASTn . The same process was followed to determine the presence of colistin resistance‐conferring mutations in mgrB, pmrAB , and phoPQ .…”

Section: Methodsmentioning

confidence: 99%

“…ACCI00000000) as the reference/wild-type strain to call single-nucleotide polymorphisms (SNPs) with tBLASTn. 27 The same process was followed to determine the presence of colistin resistance-conferring mutations in mgrB, pmrAB, and phoPQ.…”

Section: Resistome Annotation Virulome Predictions and Identificatimentioning

confidence: 99%

Genomic analysis of a multidrug‐resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon

Mbelle

Sekyere

Amoako

et al. 2019

Annals of the New York Academy of Sciences

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Whole‐genome sequence analysis was performed on a multidrug‐resistant Providencia rettgeri PR002 clinical strain isolated from the urine of a hospitalized patient in Pretoria, South Africa, in 2013. The resistome, mobilome, pathogenicity island(s), as well as virulence and heavy‐metal resistance genes of the isolate, were characterized using whole‐genome sequencing and bioinformatic analysis. PR002 had a genome assembly size of 4,832,624 bp with a GC content of 40.7%, an A/C2 plasmid replicase gene, four integrons/gene cassettes, 17 resistance genes, and several virulence and heavy metal resistance genes, confirming PR002 as a human pathogen. A novel integron, In1483, harboring the gene blaOXA‐2, was identified, with other uncharacterized class 1 integrons harboring aacA4cr and dfrA1. Aac(3′)‐IIa and blaSCO‐1, as well as blaPER‐7, sul2, and tet(B), were found bracketed by composite Tn3 transposons, and IS91, IS91, and IS4 family insertion sequences, respectively. PR002 was resistant to all antibiotics tested except amikacin, carbapenems, cefotaxime‐clavulanate, ceftazidime‐clavulanate, cefoxitin, and fosfomycin. PR002 was closely related to PR1 (USA), PRET_2032 (SPAIN), DSM_1131, and NCTC7477 clinical P. rettgeri strains, but not close enough to suggest it was imported into South Africa from other countries. Multidrug resistance in P. rettgeri is rare, particularly in clinical settings, making this case an important incident requiring urgent attention. This is also the first report of an A/C plasmid in P. rettgeri. The array, multiplicity, and diversity of resistance and virulence genes in this strain are concerning, necessitating stringent infection control, antibiotic stewardship, and periodic resistance surveillance/monitoring policies to preempt further horizontal and vertical spread of these resistance genes.

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“…The oqxA gene appears to be rare among isolates identified in Denmark, Sweden, and South Korea. Recent reports suggest that it is common in South Africa and potentially other parts of the continent but there are few studies performed in sub-Saharan Africa have sought these genes (5,(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

A large self-transmissible plasmid from Nigeria confers resistance to multiple antibacterials without a carrying cost

Monárrez

Braun

Coburn-Flynn

et al. 2019

Preprint

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Antimicrobial resistance is rapidly expanding, in a large part due to mobile genetic elements.We screened 94 fecal fluoroquinolone-resistant Escherichia coli isolates from Nigeria for six plasmid-mediated quinolone resistance (PMQR) genes. Sixteen isolates harbored at least one of the PMQR genes and four were positive for aac-6-Ib-cr. In one strain, aac-6-Ib-cr was mapped to a 125 Kb self-transmissible IncFII plasmid, pMB2, which also bears bla CTX-M-15 , seven other functional resistance genes and multiple resistance pseudogenes. We hypothesized that pMB2 had been selected by antimicrobials and that its large size would confer a growth disadvantage.However, laboratory strains carrying pMB2 grew at least as fast as isogenic strains lacking the plasmid in both rich and minimal media. We excised a 32 Kb fragment containing the sitABCD and another putative transporter, pefB, a papB homolog, and several open-reading frames of unknown function. The resulting 93 Kb mini-plasmid conferred slower growth rates and lower fitness than wildtype pMB2. Trans-complementing the deletion with the cloned sitABCD genes confirmed that they accounted for the growth advantage conferred by pMB2 in iron-depleted media. The mini-plasmid additionally conferred autoaggregation and was less transmissible and both phenotypes could be complemented with a pefB clone. pMB2 is a large plasmid with a flexible resistance region that contains multiple loci that can account for evolutionary success in the absence of antimicrobials. Ancillary functions conferred by resistance plasmids can mediate their retention and transmissibility, worsening the trajectory for antimicrobial resistance and potentially circumventing efforts to contain resistance through restricted use.

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Genomic and phenotypic characterisation of fluoroquinolone resistance mechanisms in Enterobacteriaceae in Durban, South Africa

Cited by 57 publications

References 27 publications

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Genomic analysis of a multidrug‐resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon

A large self-transmissible plasmid from Nigeria confers resistance to multiple antibacterials without a carrying cost

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