Analysis of chromosomal genes and proteins of gyrA and gyrB from Indonesian Local-Strain Salmonella enterica serovar Typhi

Introduction: Typhoid fever is an infection of the gastrointestinal tract caused by Salmonella Typhi. Ciprofloxacin is the most widely used second-line therapy; it provides good results in therapy. Indonesia has a unique resistance pattern of fluoroquinolones. Earlier studies of the gyrA and gyrB from local S. Typhi strains showed no mutation, and amino acid replacement was identified in all reported codons. In this study, we explored the whole sequence of the gyrA and gyrB further to understand the association of the unique characteristics of our local strains with fluoroquinolone resistance. Methodology: This was an analytical study with a cross-sectional approach. Isolates collection, identification, antibiotic sensitivity test, DNA extraction, gene amplification, purification, and sequencing were carried out. Bioedit was used for the analysis of sequencing data. Results: Four isolates were identified as S. Typhi. Three isolates were sensitive to nalidixic acid, ciprofloxacin, levofloxacin, and moxifloxacin. One isolate was intermediate to nalidixic acid, ciprofloxacin, levofloxacin, and resistant to moxifloxacin. The gyrA and gyrB genes were aligned with S. Typhi Ty2 reference sequence (NCBI GenBank AE014613.1). Three amino acid changes (Gly133Glu, Asn538Asp, and Thr856Ala) and one amino acid change (Ala416Ser) were found in gyrA and gyrB, respectively. Protein secondary structures of these isolates showed some changes in alpha helices, beta sheets, random coils, and beta turns, which could result in alterations of the properties of proteins. Conclusions: Some variations and protein secondary structure alterations were found in the gyrA and gyrB among local strains of S. Typhi, which might be associated with fluoroquinolone susceptibility