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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.

Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques