Abstract

The purpose of this study was to characterize mechanisms of plasmid-mediated antimicrobial resistance in Shigella boydii. S. boydii strain 2246 with resistance to ciprofloxacin, ceftriaxone and azithromycin was isolated from a human case of watery diarrhea in a Chinese public hospital. Resistance in strain 2246 to ceftriaxone and azithromycin was attributable to the presence of blaCTX-M-14, and erm(B) and mph(A), respectively, which were co-located on a multidrug-resistant (MDR) plasmid p2246-CTXM. p2246-CTXM represented a novel IncFII-type MDR plasmid with a very complex chimera structure. Its master backbone was genetically closely related to the R100 plasmid, but p2246-CTXM had evolved to integrate additional R100-unrelated backbone regions as well as massive exogenous mobile elements that carried multiple resistance determinants. In p2246-CTXM, erm(B) together with its leading peptide gene erm(C), mph(A) together with its regulatory genes mrx and mphR(A), and blaCTX-M-14 were captured by three different mobile elements Tn6295, the IS26-mph(A)-mrx-mphR(A)-IS6100 unit, and a truncated ISEcp1-blaCTX-M-14-IS903D-iroN transposition unit, respectively, all of which were harbored in a large Tn3-family transposon Tn6285. p2246-CTXM still carried additional resistance determinants mer (mercury resistance), aacA4 (aminoglycoside resistance), cmlA1 (chloramphenicol resistance), and qacED1 (quaternary ammonium compound resistance). This is the first report of identifying a clinical S. boydii strain simultaneously resistant to ciprofloxacin, ceftriaxone, and azithromycin, and determining the complete sequence of a resistance plasmid from S. boydii.

Highlights

  • Shigellosis remains a common gastrointestinal disease in both developing and industrialized countries

  • As determined by PCR screening for the major plasmid-borne quinolone-resistance, ESBL, and macrolide-resistance genes, strain 2246 harbored blaCTX−M−14, erm(B), and mph(A) rather than any of the other genes tested

  • Strains 2246 and 2246-CTXM-EC600 had the ESBL enzyme activity (Supplementary Figure S1). Both 2246 and 2246-CTXM-EC600 were resistant to piperacillin, cefazolin, cefuroxime, and ceftriaxone, but remained susceptible to piperacillin/tazobactam, imipenem and meropenem, gentamicin and amikacin, and trimethoprim/sulfamethoxazole; 2246 rather than 2246-CTXM-EC600 was resistant to ciprofloxacin and levofloxacin (Table 1)

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Summary

Introduction

Shigellosis remains a common gastrointestinal disease in both developing and industrialized countries. The causative agent of shigellosis, can be serologically grouped into four species S. flexneri, S. sonnei, S. boydii, and S. dysenteriae. Plasmid p2246-CTXM from S. boydii countries, respectively, but a shift in the dominant species from S. flexneri to S. sonnei has occurred in countries with recent rapid improvement of socioeconomic conditions (Livio et al, 2014; Lima et al, 2015). The WHO recommends ciprofloxacin as the first choice for the treatment of multidrugresistant shigellosis, while ceftriaxone and azithromycin can be used as the alternatives for both adults and children and they are preferred among young children because of the concerns regarding the adverse effects of ciprofloxacin in young children (Christopher et al, 2010)

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