Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques

Abstract

Non-human primates (NHPs) for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants isolation and antibiotic testing of enteric pathogens before treating macaques with quinolones prophylactically or therapeutically.

<p><em>Shigella</em>: Antibiotic-Resistance Mechanisms And New Horizons For Treatment</p>

“…Dissemination and acquisition of macrolide mphA resistance mechanisms in Shigella spp. has been shown to be mainly due to spread of plasmids from E. coli 140. All the discovered mphA -associated plasmids have been identified in E. coli isolates, indicating their role as a repository from which antimicrobial resistance to Shigella spp.…”

Formal Comment on “Mitigation of endemic GI-tract pathogen-mediated inflammation through development of multimodal treatment regimen and its impact on SIV acquisition in rhesus macaques” by Bochart et al. (2021)

“…However, drug resistant Shigella and Campylobacter are serious threats to human and macaque health. Not only do both Shigella and Campylobacter have decreasing rates of susceptibility to fluoroquinolones (17% and 28%, respectively) and macrolides (14% and 4%, respectively), but there are reports in both humans and macaques regarding emerging fluoroquinolone-resistant Shigella strains [ 4 , 8 – 10 ]. A recent study showed that Shigella flexneri isolated from macaques contained chromosomal and plasmid-mediated fluoroquinolone resistance [ 8 ].…”

Shigellosis and Development of Multiple Antimicrobial Resistance Mechanisms of Shigella spp.

“…Class C b-Lactamase, known as AmpC-type enzymes are encoded by both chromosomal and plasmid genes. CMY-2, a plasmid encoded AmpC b-lactamase firstly identified in S. sonnei isolates which was obtained from a dysentery outbreak in Taiwan and there after CMY-2 have been reported in several countries like China, Iran, Costa Rica and India [53][54][55] . Different AmpC genes are listed in table1.…”