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.
Highlights
Shigella spp., Shigella flexneri, are common enteric pathogens isolated from non-human primates (NHPs), including macaques, that can cause acute dysentery and are associated with chronic episodic diarrhea
Given the frequent use of quinolones and potential for zoonotic transmission, the purpose of this report is to describe the isolation of plasmid-mediated multiple-antibiotic resistant S. flexneri strains recovered from three colony-maintained macaques, and the successful eradication of these drug-resistant S. flexneri isolates
Following unsuccessful enrofloxacin treatment of paired monkeys 05-15 and 05-16, feces were collected from the cage pan and strain 063102 was cultured
Summary
Shigella spp., Shigella flexneri, are common enteric pathogens isolated from non-human primates (NHPs), including macaques, that can cause acute dysentery and are associated with chronic episodic diarrhea. Animals may not appear ill, but Shigella spp. can be cultured from normally formed, but blood-streaked feces. These animals represent Shigella spp. reservoirs capable of transmitting the pathogen to other colony-maintained NHPs and pose important zoonotic risks to research, veterinary, and zoo personnel (Fox, 1975; Tribe and Fleming, 1983; Kennedy et al, 1993). Because of the high incidence of diarrhea in newly imported NHPs, antibiotics are often given prophylactically to reduce its clinical severity. Enrofloxacin has been used to successfully eradicate Shigella spp. from a variety of NHP species housed in a laboratory and zoological setting (Line et al, 1992; Banish et al, 1993). Widespread and prophylactic use of enrofloxacin and other antibiotics act as selective pressures for the emergence of antibiotic resistant organisms
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