Dataset Information

Molecular and Physiological Characterization of Fluoroquinolone-Highly Resistant Salmonella Enteritidis Strains.

ABSTRACT: Four clinical isolates of Salmonella Enteritidis, susceptible to ciprofloxacin, and their spontaneous ciprofloxacin resistant (MICs from 8 to 16 ?g/mL) and highly resistant (MIC 2048 ?g/mL) mutants were used to gain an insight into the dynamics of development of fluoroquinolone (FQs) resistance in S. Enteritidis serovar. The first two high-frequency (i.e., mutations that occurred in each tested strain) mutations occurred in the gyrA, resulting in amino acid substitutions S83Y and S83F as well as D87G. Amino acid substitution D87G was significantly associated with the highly resistant mutants. Another high-frequency mutation, deletion in the ramRA intergenic region, was determined among the same group of highly resistant mutants. More importantly, each of these deletion mutations affected the RamR binding site. The effect of one 41 bp deletion mutation was empirically tested. The results showed that the deletion was responsible for resistance to ceftiofur and amoxicillin/clavulanic acid and decreased susceptibility to azithromycin and tetracycline. Performing gene expression assays across all ciprofloxacin susceptible groups, we found a consistent and significant upregulation of the ramA, acrB, and tolC (efflux pump associated genes) and downregulation of ompF (porin), clearly illustrating the importance of not only efflux but also porin-mediated permeability in the development of FQs resistance. Our data also showed that S. Enteritidis could acquire multiple mutations in QRDR region, further resulting in no up regulation of the ramA, acrB and tolC genes. These QRDR mutations and no activation of the AcrAB efflux pump seem to preserve the fitness of this organism compared to the S. Enteritidis strains that did not acquire multiple QRDR mutations. This report describes the dynamics of FQ-associated mutations in the highly resistant in FQ mutants in S. Enteritidis. In addition, we characterized a deletion in the ramRA integenic region, demonstrating that this frequent mutation in the highly resistant FQ mutants provide resistance or reduce susceptibility to multiple families of antibiotics.

SUBMITTER: Vidovic S

PROVIDER: S-EPMC6465633 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Molecular and Physiological Characterization of Fluoroquinolone-Highly Resistant Salmonella Enteritidis Strains.

Vidovic Sinisa S An Ran R Rendahl Aaron A

Frontiers in microbiology 20190409

Four clinical isolates of Salmonella Enteritidis, susceptible to ciprofloxacin, and their spontaneous ciprofloxacin resistant (MICs from 8 to 16 μg/mL) and highly resistant (MIC 2048 μg/mL) mutants were used to gain an insight into the dynamics of development of fluoroquinolone (FQs) resistance in S. Enteritidis serovar. The first two high-frequency (i.e., mutations that occurred in each tested strain) mutations occurred in the gyrA, resulting in amino acid substitutions S83 ...[more]

PMID: 31024504

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Project description:BackgroundSalmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes associated with iNTS disease in sSA have recently been described, often requiring treatment with fluoroquinolone antibiotics. In industrialised countries, antimicrobial use in poultry production has led to frequent fluoroquinolone resistance amongst globally prevalent enterocolitis-associated lineages.Methodology/principal findingsTwenty seven S. Enteritidis isolates from patients with iNTS disease and two poultry isolates, collected between 2007 and 2015 in the Ashanti region of Ghana, were whole-genome sequenced. These isolates, notable for a high rate of diminished ciprofloxacin susceptibility (DCS), were placed in the phyletic context of 1,067 sequences from the Public Health England (PHE) S. Enteritidis genome database to understand whether DCS was associated with African or globally-circulating clades of S. Enteritidis. Analysis showed four of the major S. Enteritidis clades were represented, two global and two African. All thirteen DCS isolates, containing a single gyrA mutation at codon 87, belonged to a global PT4-like clade responsible for epidemics of poultry-associated enterocolitis. Apart from two DCS isolates, which clustered with PHE isolates associated with travel to Spain and Brazil, the remaining DCS isolates, including one poultry isolate, belonged to two monophyletic clusters in which gyrA 87 mutations appear to have developed within the region.Conclusions/significanceExtensive phylogenetic diversity is evident amongst iNTS disease-associated S. Enteritidis in Ghana. Antimicrobial resistance profiles differed by clade, highlighting the challenges of devising empirical sepsis guidelines. The detection of fluoroquinolone resistance in phyletically-related poultry and human isolates is of major concern and surveillance and control measures within the region's burgeoning poultry industry are required to protect a human population at high risk of iNTS disease.

Dataset Information

Molecular and Physiological Characterization of Fluoroquinolone-Highly Resistant Salmonella Enteritidis Strains.

Publications

Molecular and Physiological Characterization of Fluoroquinolone-Highly Resistant <i>Salmonella</i> Enteritidis Strains.

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