Extensive Drug-Resistant Salmonella enterica Isolated From Poultry and Humans: Prevalence and Molecular Determinants Behind the Co-resistance to Ciprofloxacin and Tigecycline

Abstract

The emergence of extensive drug-resistant (XDR) <i>Salmonella</i> in livestock animals especially in poultry represents a serious public health and therapeutic challenge. Despite the wealth of information available on <i>Salmonella</i> resistance to various antimicrobials, there have been limited data on the genetic determinants of XDR <i>Salmonella</i> exhibiting co-resistance to ciprofloxacin (CIP) and tigecycline (TIG). This study aimed to determine the prevalence and serotype diversity of XDR <i>Salmonella</i> in poultry flocks and contact workers and to elucidate the genetic determinants involved in the co-resistance to CIP and TIG. Herein, 115 <i>Salmonella enterica</i> isolates of 35 serotypes were identified from sampled poultry (100/1210, 8.26%) and humans (15/375, 4.00%), with the most frequent serotype being <i>Salmonella</i> Typhimurium (26.96%). Twenty-nine (25.22%) <i>Salmonella enterica</i> isolates exhibited XDR patterns; 25 out of them (86.21%) showed CIP/TIG co-resistance. Exposure of CIP- and TIG-resistant isolates to the carbonyl cyanide 3-chlorophenylhydrazone (CCCP) efflux pump inhibitor resulted in an obvious reduction in their minimum inhibitory concentrations (MICs) values and restored the susceptibility to CIP and TIG in 17.24% (5/29) and 92% (23/25) of the isolates, respectively. Molecular analysis revealed that 89.66% of the isolates contained two to six plasmid-mediated quinolone resistance genes with the predominance of <i>qepA</i> gene (89.66%). Mutations in the <i>gyrA</i> gene were detected at codon S83 (34.62%) or D87 (30.77%) or both (34.62%) in 89.66% of XDR <i>Salmonella</i>. The <i>tet</i>(A) and <i>tet</i>(X4) genes were detected in 100% and 3.45% of the XDR isolates, respectively. Twelve TIG-resistant XDR <i>Salmonella</i> had point mutations at codons 120, 121, and 181 in the <i>tet(A)</i> interdomain loop region. All CIP and TIG co-resistant XDR <i>Salmonella</i> overexpressed <i>ramA</i> gene; 17 (68%) out of them harbored 4-bp deletion in the <i>ramR</i> binding region (T-288/A-285). However, four CIP/TIG co-resistant isolates overexpressed the <i>oqxB</i> gene. In conclusion, the emergence of XDR <i>S. enterica</i> exhibiting CIP/TIG co-resistance in poultry and humans with no previous exposure to TIG warrants an urgent need to reduce the unnecessary antimicrobial use in poultry farms in Egypt.