Chromosomal and plasmid-mediated fluoroquinolone resistance in human Salmonella enterica infection in Ghana

Abstract

BackgroundSalmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana.MethodsThis was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR.ResultsOf 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 μg/ml.ConclusionThis study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.

In-vitro Antimicrobial Activity of the Combined Effect of Kalanchoe Crenata and Vernonia Amygdalina on Salmonella Species

“…Poor food hygiene, poverty and inadequate supply of clean water has resulted in the increase in typhoid infections and acute gastroenteritis in African [8]. In recent years multidrug resistance to the typhoid infection has increased worldwide [9][10][11].…”

Inhibitory concentrations of ciprofloxacin induce an adaptive response promoting the intracellular survival ofSalmonellaTyphimurium

“…This potent group of bactericidal chemicals act by binding to bacterial type II topoisomerases DNA gyrase I (GyrA and GyrB) and Topoisomerase IV (ParC and ParE) to disrupt DNA supercoiling, which leads to cell death (4)(5)(6). Resistance to fluoroquinolones is associated with specific mutations in the gyrA, gyrB, parC and/or parE genes, although the extent of resistance can be further modulated by mutations in efflux pumps and porins and also via the acquisition of plasmid-mediated quinolone resistance (PMQR) genes (7)(8)(9)(10)(11).…”

Quinolone resistance amongSalmonellaKentucky and Typhimurium isolates in Tunisia: first report ofSalmonellaTyphimurium ST34 in Africa andqnrB19in Tunisia

“…2015; Acheampong et al . 2019). In recent years, the Kentucky serotype emerged in Egypt and spread throughout Africa and the Middle East (between 2002 and 2008) (Le Hello et al .…”

“…2003; Acheampong et al . 2019). Importantly, isolates with ciprofloxacin minimum inhibitory concentrations (MICs) as low as 0·125 µg ml −1 have been associated with treatment failure (Aarestrup et al .…”