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Prevalence and mechanism of fluoroquinolone resistance in clinical isolates of Proteus mirabilis in Japan.

ABSTRACT: Fluoroquinolone (FQ) and cephalosporin (CEP) resistance among Enterobacteriaceae has been increasingly reported. FQ resistance occurs primarily through mutations in DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE). CEP resistance in Enterobacteriaceae is mainly due to the production of CTX-M type extended-spectrum ?-lactamases. Although prevalence and mechanisms of FQ and CEP resistance in Enterobacteriaceae such as Escherichia coli have been well studied, little is known about Proteus mirabilis in Japan. In this study, we assessed the prevalence and mechanism of FQ resistance in Japanese clinical isolates of P. mirabilis. We collected 5845 P. mirabilis isolates from eight hospitals between 2000 and 2013. Prevalence of FQ resistance was calculated as the annual average percentage of all P. mirabilis isolates. We selected 50 isolates exhibiting susceptibility, intermediate resistance, or resistance to levofloxacin (LVX) and identified amino acid substitutions in GyrA, GyrB, ParC, and ParE. The prevalence of FQ-resistant P. mirabilis gradually increased from 2001 to 2004, reaching 16.6% in 2005, and has remained relatively high (13.3-17.5%) since then. Low-level LVX-resistant strains (MIC, 8-16 mg/L) showed significant changes in GyrB (S464Y or -I, or E466D). High-level LVX-resistant strains (MIC, 32-128 mg/L) displayed significant changes in GyrA (E87K) and ParE (D420N). The highest-level LVX-resistant strains (MIC, ? 256 mg/L) presented significant changes in GyrA (E87K or -G), GyrB (S464I or -F), and ParE (D420N). Our findings suggest that substitutions in GyrA (E87) and ParE (D420) have played an important role in the emergence of high-level LVX-resistant P. mirabilis isolates (MIC, ? 32 mg/L) in Japan.

SUBMITTER: Nakano R

PROVIDER: S-EPMC6403068 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Project description:ObjectiveProteus mirabilis is the one of most important pathogens of catheter-associated urinary tract infections. The emergence of multidrug-resistant (MDR) P. mirabilis severely limits antibiotic treatments, which poses a public health risk. This study aims to investigate the resistance characteristics and virulence potential for a collection of P. mirabilis clinical isolates.Methods and resultsAntibiotic susceptibility testing revealed fourteen MDR strains, which showed high resistance to most β-lactams and trimethoprim/sulfamethoxazole, and a lesser extent to quinolones. All the MDR strains were sensitive to carbapenems (except imipenem), ceftazidime, and amikacin, and most of them were also sensitive to aminoglycosides. The obtained MDR isolates were sequenced using an Illumina HiSeq. The core genome-based phylogenetic tree reveals the high genetic diversity of these MDR P. mirabilis isolates and highlights the possibility of clonal spread of them across China. Mobile genetic elements SXT/R391 ICEs were commonly (10/14) detected in these MDR P. mirabilis strains, whereas the presence of resistance island PmGRI1 and plasmid was sporadic. All ICEs except for ICEPmiChn31006 carried abundant antimicrobial resistance genes (ARGs) in the HS4 region, including the extended-spectrum β-lactamase (ESBL) gene blaCTX-M-65. ICEPmiChn31006 contained the sole ARG blaCMY-2 and was nearly identical to the global epidemic ICEPmiJpn1. The findings highlight the important roles of ICEs in mediating the spread of ARGs in P. mirabilis strains. Additionally, these MDR P. mirabilis strains have great virulence potential as they exhibited significant virulence-related phenotypes including strong crystalline biofilm, hemolysis, urease production, and robust swarming motility, and harbored abundant virulence genes.ConclusionIn conclusion, the prevalence of MDR P. mirabilis with high virulence potential poses an urgent threat to public health. Intensive monitoring is needed to reduce the incidence of infections by MDR P. mirabilis.

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Prevalence and mechanism of fluoroquinolone resistance in clinical isolates of Proteus mirabilis in Japan.

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