Quinolone Resistance Determinants of Clinical Salmonella Enteritidis in Thailand

Abstract

Salmonella Enteritidis has emerged as a global concern regarding quinolone resistance and invasive potential. Although quinolone-resistant S. Enteritidis has been observed with high frequency in Thailand, information on the mechanism of resistance acquisition is limited. To elucidate the mechanism, a total of 158 clinical isolates of nalidixic acid (NAL)-resistant S. Enteritidis were collected throughout Thailand, and the quinolone resistance determinants were investigated in the context of resistance levels to NAL, norfloxacin (NOR), and ciprofloxacin (CIP). The analysis of point mutations in type II topoisomerase genes and the detection of plasmid-mediated quinolone resistance genes showed that all but two harbored a gyrA mutation, the qnrS1 gene, or both. The most commonly affected codon in mutant gyrA was 87, followed by 83. Double codon mutation in gyrA was found in an isolate with high-level resistance to NAL, NOR, and CIP. A new mutation causing serine to isoleucine substitution at codon 83 was identified in eight isolates. In addition to eighteen qnrS1-carrying isolates showing nontypical quinolone resistance, one carrying both the qnrS1 gene and a gyrA mutation also showed a high level of resistance. Genotyping by multilocus variable number of tandem repeat analysis suggested a possible clonal expansion of NAL-resistant strains nationwide. Our data suggested that NAL-resistant isolates with single quinolone resistance determinant may potentially become fluoroquinolone resistant by acquiring secondary determinants. Restricted therapeutic and farming usage of quinolones is strongly recommended to prevent the emergence of fluoroquinolone-resistant isolates.

Frequency of Antimicrobial Resistance Genes in Salmonella From Brazil by in silico Whole-Genome Sequencing Analysis: An Overview of the Last Four Decades

“…Salmonella Enteritidis (34.7%, 323/930) and S. Typhimurium (20.4%, 190/930) were the most commonly found serovars among the WGS deposited from Brazil. Salmonella Enteritidis and S. Typhimurium are the most common serovars reported in human sources in Latin America between 2001 and 2014 ( Hendriksen et al, 2011 ; Quesada et al, 2016 ), in the United States in 2016 ( Centers for Disease Control and Prevention [CDC], 2018 ), in member countries of the European Union in 2017 ( European Food Safety Authority [EFSA], and European Centre for Disease Prevention, and Control [ECDC], 2018 ), and in the majority of the researches and the studies regarding Salmonella around the world ( Asif et al, 2017 ; Borges et al, 2017 ; Campioni et al, 2017 ; Muvhali et al, 2017 ; Utrarachkij et al, 2017 ; Zhang et al, 2017 ; Magdy et al, 2019 ). The high presence of these serovars among the WGS deposited from Brazil may be related to the fact that the majority of researches about Salmonella in Brazil also concerns S. Enteritidis and S. Typhimurium and likewise worldwide ( Campioni et al, 2017 ; Almeida et al, 2018 ; Panzenhagen et al, 2018a , b ; Ritter et al, 2019 ).…”

Comparative Genomics and Phenotypic Investigations Into Antibiotic, Heavy Metal, and Disinfectant Susceptibilities of Salmonella enterica Strains Isolated in Australia

“…Resistance to nalidixic acid was identified in one isolate in this study that possessed a SNP in the QRDR of DNA gyrase gene gyrA resulting in amino acid change Asp87Gly. Mutations to the Quinolone Resistance Determining Regions (QRDR) in DNA gyrase genes, gyrA and gyrB , and DNA Topoisomerase genes, parC and parE , have been detected in fluoroquinolone-resistant strains of Salmonella , including those resistant to ciprofloxacin, norfloxacin and nalidixic acid (Gal-Mor et al, 2010; Utrarachkij et al, 2017; Vital et al, 2017). Nalidixic acid is not currently used as a treatment option of salmonellosis in Australia, with amoxicillin, trimethoprim-sulfamethoxazole and azithromycin used in human cases and apromycin used in calves, pigs and broiler infections (Lean et al, 2013).…”

WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium

“…In a past epidemiological study, the number of nontyphoidal Salmonella strains containing amino acid substitutions at position 87 was greater than that with amino acid substitutions at position 83. [17] In light of this, WQ-3810, with a higher antibacterial activity than ciprofloxacin and a higher antimicrobial activity against strains with amino acid substitutions at position 87, will likely be an effective quinolone antibacterial drug.…”

“…Mutations have been frequently reported at codons 83 and 87 of the amino acid sequence of GyrA in quinolone-resistant Salmonella. [16][17][18][19] Amino acids at these positions are considered to be strongly involved in the binding to quinolones. [20][21][22] Therefore, it is critical to find quinolones showing high affinity to DNA gyrases with amino acid substitutions at positions 83 and 87.…”