Clinical use of tigecycline may contribute to the widespread dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae strains

ABSTRACT

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses grave threats to human health. These strains increased dramatically in clinical settings in China in the past few years but not in other parts of the world. Four isogenic K. pneumoniae strains, including classical K. pneumoniae, carbapenem-resistant K. pneumoniae (CRKP), hypervirulent K. pneumoniae (hvKP) and CR-hvKP, were created and subjected to phenotypic characterization, competition assays, mouse sepsis model and rat colonization tests to investigate the mechanisms underlying the widespread nature of CR-hvKP in China. Acquisition of virulence plasmid led to reduced fitness and abolishment of colonization in the gastrointestinal tract, which may explain why hvKP is not clinically prevalent after its emergence for a long time. However, tigecycline treatment facilitated the colonization of hvKP and CR-hvKP and reduced the population of Lactobacillus spp. in animal gut microbiome. Feeding with Lactobacillus spp. could significantly reduce the colonization of hvKP and CR-hvKP in the animal gastrointestinal tract. Our data implied that the clinical use of tigecycline to treat carbapenem-resistant K. pneumoniae infections facilitated the high spread of CR-hvKP in clinical settings in China and demonstrated that Lactobacillus spp. was a potential candidate for anticolonization strategy against CR-hvKP.

KEYWORDS:

• Carbapenem-resistant hypervirulent Klebsiella pneumoniae
• tigecycline
• virulence plasmid
• fitness
• colonization

Acknowledgements

MMX performed the experiments and drafted the manuscript; LWY and KCC participated in animal colonization experiments and faecal microbiome analysis; QX, CY and XNC helped with animal experiments; EWCC edited the manuscript; FYL supervised the animal colonization experiments; and SC edited the manuscript and supervised the project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The complete sequence of virulence plasmid p16ZR-26-Vir has been deposited into the GenBank database under the accession number OP168824. Metagenomic sequencing data has been deposited into the NCBI database under the BioProject accession number PRJNA909428.

Additional information

Funding

This work was supported by the Research Grants Council of Hong Kong Special Administrative Region, China (Project Reference Number: T11-104/22-R, 11100321 and 11100922).