Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying bla VIM-2 and bla KPC-2 Genes That Spread on Different Genetic Environment in Colombia

Ana M Rada; Elsa De La Cadena; Carlos A Agudelo; Christian Pallares; Eliana Restrepo; Adriana Correa; María V Villegas; Cesar Capataz

doi:10.3389/fmicb.2021.663020

Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying bla _VIM-2 and bla _KPC-2 Genes That Spread on Different Genetic Environment in Colombia

Front Microbiol. 2021 Aug 27:12:663020. doi: 10.3389/fmicb.2021.663020. eCollection 2021.

Authors

Ana M Rada^{1

2}, Elsa De La Cadena³, Carlos A Agudelo^{4

5}, Christian Pallares³, Eliana Restrepo¹, Adriana Correa⁶, María V Villegas³, Cesar Capataz⁷

Affiliations

¹ Department of Microbiology and Parasitology, Bacteria and Cancer Group, Universidad de Antioquia, Medellín, Colombia.
² Faculad de Ciencias de la Salud, Biociencias Group, Institución Universitaria Colegio Mayor de Antioquia, Medellín, Colombia.
³ Grupo de Resistencia Antimicrobiana y Epidemiología Hospitalaria, Universidad El Bosque, Bogotá, Colombia.
⁴ Clinica Universitaria Bolivariana, Medellín, Colombia.
⁵ School of Health Sciences, Universidad Pontificia Bolivariana, Medellín, Colombia.
⁶ Facultad de Ciencias Básicas, Universidad Santiago de Cali, Cali, Colombia.
⁷ Fundación Clínica del Norte, Bello, Colombia.

Abstract

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with an increase in the frequency of infections caused by multidrug resistant (MDR) and extensively drug resistant (XDR) strains, limiting the available therapeutic options. The most troublesome resistance is the acquisition and production of carbapenemases such as Verona integron-encoded metallo-β-lactamases (VIM), the most frequent and widespread, and the Klebsiella pneumoniae carbapenemases (KPC), which has continuously spread in the last decade. Its dissemination is linked to their location on mobile genetic elements (MGEs). In Colombia, VIM and KPC have been increasing in its frequency showing major successful dissemination. In this article, we molecularly characterized and analyzed the genetic context of bla _VIM and bla _KPC in carbapenem-resistant P. aeruginosa (CRPA) isolates from infected and colonized patients in two tertiary-care hospitals, one in Medellín and the other in a municipality close to Medellín, both areas with high carbapenemase endemicity in Colombia (2013-2015). Using whole-genome sequencing (WGS), we identified a remarkable variety of genetic backgrounds in these MDR P. aeruginosa isolates carrying bla _KPC- ₂ and bla _VIM- ₂. There were a diversity of class 1 integron and variations in the gene cassettes associated to bla _VIM- ₂, as well as a possible event of spread of bla _KPC- ₂ mediated by a plasmid that contained part of Tn4401b in one infection case. The dissemination of bla _VIM- ₂ and bla _KPC- ₂ in P. aeruginosa in this area in Colombia has been strongly influenced by successful international clones, carrying these genes and additional determinants of resistance on MGEs, accompanied by gene rearrangement under an antimicrobial selection pressure. These findings emphasize the need to implement control strategies based on rational antibiotic use.

Keywords: Pseudomonas aeruginosa; blaKPC–2; blaVIM–2; genetic diversity; integron; plasmid.