Genomic Analysis of Ciprofloxacin-Resistant Salmonella enterica Serovar Kentucky ST198 From Spanish Hospitals.

Miriam Alkorta,Javier Fernández,María De Toro,Margarita Bances,Elizabeth Prieto,Silvia Hernáez,Rosaura Rodicio,Xenia Vázquez,M Rosario Rodicio,Pilar Lumbreras,Pedro De La Iglesia

doi:10.3389/fmicb.2021.720449

Abstract

Salmonella enterica serovar Kentucky (S. Kentucky) with sequence type (ST) 198 and highly resistant to ciprofloxacin (ST198-CipR) has emerged as a global MDR clone, posing a threat to public health. In the present study, whole genome sequencing (WGS) was applied to characterize all CipR S. Kentucky detected in five Spanish hospitals during 2009–2018. All CipR isolates (n = 13) were ST198 and carried point mutations in the quinolone resistance-determining regions (QRDRs) of both gyrA (resulting in Ser83Phe and Asp87Gly, Asp87Asn, or Asp87Tyr substitutions in GyrA) and parC (with Thr57Ser and Ser80Ile substitutions in ParC). Resistances to other antibiotics (ampicillin, chloramphenicol, gentamicin, streptomycin, sulfonamides, and tetracycline), mediated by the blaTEM–1B, catA1, aacA5, aadA7, strA, strB, sul1, and tet(A) genes, and arranged in different combinations, were also observed. Analysis of the genetic environment of the latter resistance genes revealed the presence of multiple variants of SGI1 (Salmonella genomic island 1)-K and SGI1-P, where all these resistance genes except catA1 were placed. IS26 elements, found at multiple locations within the SGI1 variants, have probably played a crucial role in their generation. Despite the wide diversity of SGI1-K- and SGI1-P-like structures, phylogenetic analysis revealed a close relationship between isolates from different hospitals, which were separated by a minimum of two and a maximum of 160 single nucleotide polymorphisms. Considering that S. enterica isolates resistant to fluoroquinolones belong to the high priority list of antibiotic-resistant bacteria compiled by the World Health Organization, continuous surveillance of the S. Kentucky ST198-CIPR clone is required.

Highlights

Salmonella enterica is one of the major causes of bacterial gastrointestinal infections in humans, worldwide, with estimates of 93.8 million cases each year and 155,000 deaths (Majowicz et al, 2010)
The assembly size of the sequenced genomes ranged from 4.785 Mb (HUD 1/14) to 4.857 Mb (HUA 10/18), and MLST performed in silico assigned all isolates to ST198
Kentucky ST198 resistant to ciprofloxacin and carrying SGI1-K- and SGI1-P-like structures were detected in five hospitals from Northern Spain

Summary

Introduction

Salmonella enterica is one of the major causes of bacterial gastrointestinal infections in humans, worldwide, with estimates of 93.8 million cases each year and 155,000 deaths (Majowicz et al, 2010). The high rate of resistance against traditional antimicrobials has prompted the use of newer broad-spectrum drugs, like third generation cephalosporins and fluoroquinolones (Hohmann, 2001), which are recommended by therapeutic international and national (including Spanish) guidelines as first choices for Salmonella severe infections (Gilbert et al, 2021; Mensa and Soriano, 2021). These compounds are listed by the World Health Organization (WHO) as “critically important antimicrobials” with the highest priority for human medicine (World Health Organization [WHO], 2016). Resistance to ampicillin, sulfonamides, tetracyclines ( common in other S. enterica serovars) and gentamicin (infrequently found in Salmonella) are very high as well, leading to multidrug resistance (MDR)

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