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

Xenia Vázquez; Javier Fernández; Margarita Bances; Pilar Lumbreras; Miriam Alkorta; Silvia Hernáez; Elizabeth Prieto; Pedro de la Iglesia; María de Toro; M Rosario Rodicio; Rosaura Rodicio

doi:10.3389/fmicb.2021.720449

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

Front Microbiol. 2021 Oct 5:12:720449. doi: 10.3389/fmicb.2021.720449. eCollection 2021.

Authors

Xenia Vázquez^{1

2}, Javier Fernández^{2

3

4}, Margarita Bances⁵, Pilar Lumbreras², Miriam Alkorta⁶, Silvia Hernáez⁷, Elizabeth Prieto⁸, Pedro de la Iglesia⁹, María de Toro¹⁰, M Rosario Rodicio^{1

2}, Rosaura Rodicio^{2

11}

Affiliations

¹ Área de Microbiología, Departamento de Biología Funcional, Universidad de Oviedo (UO), Oviedo, Spain.
² Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
³ Servicio de Microbiología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
⁴ Research and Innovation, Artificial Intelligence and Statistical Department, Pragmatech AI Solutions, Oviedo, Spain.
⁵ Laboratorio de Salud Pública (LSP) del Principado de Asturias, Dirección General de Salud Pública, Oviedo, Spain.
⁶ Servicio de Microbiología, Hospital Universitario Donostia (HUD)-IIS Biodonostia, San Sebastián, Spain.
⁷ Servicio de Microbiología, Hospital Universitario de Álava (HUA), Vitoria-Gasteiz, Spain.
⁸ Servicio de Microbiología, Hospital Universitario San Agustín, Avilés, Spain.
⁹ Servicio de Microbiología, Hospital Universitario de Cabueñes, Gijón, Spain.
¹⁰ Plataforma de Genómica y Bioinformática, Centro de Investigación Biomédica de La Rioja (CIBIR), Logroño, Spain.
¹¹ Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo (UO), Oviedo, Spain.

Abstract

Salmonella enterica serovar Kentucky (S. Kentucky) with sequence type (ST) 198 and highly resistant to ciprofloxacin (ST198-Cip ^R ) 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 Cip ^R S. Kentucky detected in five Spanish hospitals during 2009-2018. All Cip ^R 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 bla _TEM- ₁ _B , 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-CIP ^R clone is required.

Keywords: IS26; SGI1-K; ST198; Salmonella enterica serovar Kentucky; fluoroquinolone resistance; multidrug resistance; phylogenetic analysis; whole genome sequencing.