title: Genetic markers associated with resistance to beta-lactam and quinolone antimicrobials in non-typhoidalSalmonellaisolates from humans and animals in central Ethiopia.
abstract: BACKGROUND
  Beta-lactam and quinolone antimicrobials are commonly used for treatment of infections caused by non-typhoidalSalmonella(NTS) and other pathogens. Resistance to these classes of antimicrobials has increased significantly in the recent years. However, little is known on the genetic basis of resistance to these drugs inSalmonellaisolates from Ethiopia.
  
  
  METHODS
  Salmonellaisolates with reduced susceptibility to beta-lactams (n= 43) were tested for genes encoding for beta-lactamase enzymes, and those resistant to quinolones (n= 29) for mutations in the quinolone resistance determining region (QRDR) as well as plasmid mediated quinolone resistance (PMQR) genes using PCR and sequencing.
  
  
  RESULTS
  Beta-lactamase genes (bla) were detected in 34 (79.1%) of the isolates. The dominantblagene wasblaTEM, recovered from 33 (76.7%) of the isolates, majority being TEM-1 (24, 72.7%) followed by TEM-57, (10, 30.3%). TheblaOXA-10 andblaCTX-M-15 were detected only in a singleS.Concord human isolate. Double substitutions ingyrA (Ser83-Phe + Asp87-Gly) as well asparC (Thr57-Ser + Ser80-Ile) subunits of the quinolone resistance determining region (QRDR) were detected in allS.Kentucky isolates with high level resistance to both nalidixic acid and ciprofloxacin. Single amino acid substitutions, Ser83-Phe (n= 4) and Ser83-Tyr (n= 1) were also detected in thegyrA gene. An isolate ofS. Miami susceptible to nalidixic acid but intermediately resistant to ciprofloxacin had Thr57-Ser and an additional novel mutation (Tyr83-Phe) in theparC gene. Plasmid mediated quinolone resistance (PMQR) genes investigated were not detected in any of the isolates. In some isolates with decreased susceptibility to ciprofloxacin and/or nalidixic acid, no mutations in QRDR or PMQR genes were detected. Over half of the quinolone resistant isolates in the current study 17 (58.6%) were also resistant to at least one of the beta-lactam antimicrobials.
  
  
  CONCLUSIONS
  Acquisition ofblaTEM was the principal beta-lactamase resistance mechanism and mutations within QRDR ofgyrA andparC were the primary mechanism for resistance to quinolones. Further study on extended spectrum beta-lactamase and quinolone resistance mechanisms in other gram negative pathogens is recommended.
authors.affiliation: Aklilu Lemma Institute of Pathobiology, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.
authors.forename: Tadesse
authors.initials: T
authors.lastname: Eguale
authors.affiliation: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P O Box 30709, Nairobi, Kenya.
authors.forename: Josephine
authors.initials: J
authors.lastname: Birungi
authors.affiliation: Department of Microbiology, Immunology & Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Churchill Avenue, P.O. Box 9086, Addis Ababa, Ethiopia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Asrat
authors.affiliation: ICIPE-African Insect Science for Food and Health, P.O. Box 30772-00100, Nairobi, Kenya.
authors.forename: Moses N
authors.initials: MN
authors.lastname: Njahira
authors.affiliation: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P O Box 30709, Nairobi, Kenya.
authors.forename: Joyce
authors.initials: J
authors.lastname: Njuguna
authors.affiliation: Department of Veterinary Preventive Medicine, The Ohio State University, 1920 Coffey Rd., Columbus, OH 43210 USA.
authors.forename: Wondwossen A
authors.initials: WA
authors.lastname: Gebreyes
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, The Ohio State University, Biomedical Research Tower, 460 West 12th, Columbus, OH 432101214 USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Gunn
authors.affiliation: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P O Box 30709, Nairobi, Kenya.
authors.forename: Appolinaire
authors.initials: A
authors.lastname: Djikeng
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Churchill Avenue, P.O. Box 1176, Addis Ababa, Ethiopia.
authors.forename: Ephrem
authors.initials: E
authors.lastname: Engidawork
keywords: Animal strains; Antimicrobial resistance; Beta-lactamase; Ethiopia; Fluoroquinolone; Human strains; Mechanisms of resistance; Non-typhoidal Salmonella; Quinolone