Co-harboring of Novel bla KPC-2 Plasmid and Integrative and Conjugative Element Carrying Tn6203 in Multidrug-Resistant Pseudomonas aeruginosa.

Heng Cai,Belinda Loh,Sebastian Leptihn,Yunsong Yu,Yiwei Zhu,Xiaoting Hua,Yue Li,Dandan Hu

doi:10.3389/fmicb.2021.674974

Abstract

Many strains of the opportunistic pathogen Pseudomonas aeruginosa have acquired resistance to multiple antibiotics. Carbapenem-resistant P. aeruginosa poses a global healthcare problem due to limited therapeutic options for the treatment of infections. Plasmids and integrative and conjugative elements (ICEs) are the major vectors of antibiotic-resistance gene transfer. In our study, four carbapenem-resistant strains of P. aeruginosa were isolated from the same patient in a tertiary referral hospital in China, one of these was resistant to gentamicin and tobramycin. In this strain P33, we observed a non-transferable plasmid, pP33-2, carrying a novel blaKPC−2 gene segment (ISKpn27-blaKPC−2-ISKpn6-korC-ORF-klcA-IS26), which we concluded to have been formed by IS26-mediated gene cluster translocation. In addition, by comparing the chromosomes of the P. aeruginosa strains that belong to the same sequence type, we identified an ICE, ICEP33, adjacent to a prophage. The attL site of ICEP33 is identical to the terminal part of the attR site of the prophage. The ICEP33 element contains the transposon Tn6203, which encodes antibiotic and metal resistance genes. The insertion of ICEP33 in the chromosome mediates resistance to multiple antibiotics. Our study contributes to the understanding of the acquisition of antibiotic resistance in P. aeruginosa facilitated by mobile genetic elements.

Highlights

Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a threat to human health, causing severe acute and chronic infections in hospitalized and immunocompromised patients (Horcajada et al, 2019)
P20 was isolated from the rectal swab on the day of admission; P22 and P23 were isolated from the rectal swab and throat swab on the fifth day after admission, respectively; and P33 was isolated from the tracheotomy tube on the twelfth day
The horizontal transmission of the antibiotic resistance genes in those strains was hypothesized to be mediated by mobile elements IS26 and integrative and conjugative elements (ICEs)

Summary

Introduction

Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a threat to human health, causing severe acute and chronic infections in hospitalized and immunocompromised patients (Horcajada et al, 2019). While carbapenems are currently one of the most important classes of antibiotics for the treatment of MDR P. aeruginosa strains, they are ineffective in nearly 30% of clinical cases in China (Hu et al, 2019a). The acquisition of carbapenemase genes is one of the main mechanisms of resistance to carbapenems (van Duin and Doi, 2017). Klebsiella pneumoniae carbapenemases (KPCs), belonging to Ambler’s class A beta-lactamases, have spread extensively and are often horizontally transferred via plasmids (Munoz-Price et al, 2013; Chen et al, 2014b). The previous reports have documented KPC-2-producing P. aeruginosa ST463 in Hangzhou, China, and typically, the blaKPC−2 genes were plasmid located (Hu et al, 2015b, 2019b). In addition to intrinsic resistances and chromosomal mutations, mobile genetic elements, such as plasmids and integrative and conjugative elements (ICEs), are responsible for spreading resistance genes to P. aeruginosa strains (Botelho et al, 2019)

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Conclusion