title: GyrA ser83 and ParC trp106 Mutations in Salmonella enterica Serovar Typhi Isolated from Typhoid Fever Patients in Tertiary Care Hospital.
abstract: BACKGROUND
  Typhoid fever is endemic in India and other developing countries, causing major public health problems with high morbidity and mortality. The resistance of Salmonella enterica serovar Typhi (S. Typhi) towards commonly prescribed antimicrobials is increasing in developing countries. However, there have been several reports of the therapeutic failure of fluoroquinolones in patients with Salmonella infection. Resistance to quinolones/ fluoroquinolones commonly arises due to target site mutation.
  
  
  OBJECTIVE
  The present study was planned to analyze mutation in Quinolone Resistance Determining Region (QRDR) of quinolone resistant Salmonella isolates.
  
  
  METHODS
  A total of 133 S. Typhi isolates (blood (n = 131), stool (n=1) and bone marrow aspirate (n=1)) from tertiary care hospitals in Chennai and Puducherry, were included in this study. Minimum Inhibitory Concentrations (MIC) were carried out according to the Clinical Laboratory Standard Institute (CLSI)guidelines 2014. Mutations in gyrA and parC genes were analyzed by PCR-RFLP (Restriction Fragment Length Polymorphism) method followed by DNA sequencing.
  
  
  RESULTS
  Of the 133 S. Typhi, 99.2% were resistant to nalidixic acid and 21% were resistant to ciprofloxacin by MIC method. 94% of isolates showed Ser 83 mutation in gyrA and 21.8% of isolates showed Trp106-Gly mutation in parC.
  
  
  CONCLUSIONS
  Mutations in gyrA and parC genes are highly prevalent among Salmonella species. Irrational use of fluoroquinolones may increase the accumulation of mutations in the DNA gyrase and topoisomerase encoding genes, which lead to the emergence of high level fluoroquinolone-resistant Salmonella strains in future.
authors.affiliation: Scientist-C, Model Rural Health Research Unit, National Institute of Epidemiology (ICMR), Primary Health Centre , Nadukallur, Tirunelveli, Tamil Nadu, India .
authors.forename: Muthu
authors.initials: M
authors.lastname: Gopal
authors.affiliation: Research Scholar, Department of Microbiology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras , Taramani, Chennai, India .
authors.forename: Sathishkumar
authors.initials: S
authors.lastname: Elumalai
authors.affiliation: Scientist-C, Centre for Drug Discovery and Development, Sathyabama University , Jeppiaar Nagar, Rajiv Gandhi Road, Chennai, India .
authors.forename: Suresh
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Scientist, National Hub for Healthcare Instrumentation Development, Centre for Biotechnology, Anna University , Chennai, India .
authors.forename: Vishnuprabu
authors.initials: V
authors.lastname: Durairajpandian
authors.affiliation: Professor, Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras , Taramani, Chennai, India .
authors.forename: Munirajan Arasambattu
authors.initials: MA
authors.lastname: Kannan
authors.affiliation: Specialist Cum Head of Department of Microbiology, ESIC Hospital , K.K.Nagar, Chennai, Tamil Nadu, India .
authors.forename: Esthermary
authors.initials: E
authors.lastname: Selvam
authors.affiliation: Assistant Professor, Department of Microbiology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras , Taramani, Chennai, India .
authors.forename: Srivani
authors.initials: S
authors.lastname: Seetharaman
keywords: Ciprofloxacin; MDRST; NARST; Nalidixic acid; QRDR