Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Whole Genome Sequencing Uncovers the Genetic Determinants of Colistin Resistance in Multi-Drug Resistant Klebsiella pneumoniae Isolated from Patients Admitted in the ICU of a Tertiary Care Hospital in Kampala, Uganda

Version 1 : Received: 20 October 2023 / Approved: 23 October 2023 / Online: 23 October 2023 (13:26:48 CEST)

How to cite: Magulye, M.A.K.; Maghembe, R.S.; Sekyanzi, S.; Achan, B.; Mwesigwa, S.; Katagirya, E. Whole Genome Sequencing Uncovers the Genetic Determinants of Colistin Resistance in Multi-Drug Resistant Klebsiella pneumoniae Isolated from Patients Admitted in the ICU of a Tertiary Care Hospital in Kampala, Uganda. Preprints 2023, 2023101454. https://doi.org/10.20944/preprints202310.1454.v1 Magulye, M.A.K.; Maghembe, R.S.; Sekyanzi, S.; Achan, B.; Mwesigwa, S.; Katagirya, E. Whole Genome Sequencing Uncovers the Genetic Determinants of Colistin Resistance in Multi-Drug Resistant Klebsiella pneumoniae Isolated from Patients Admitted in the ICU of a Tertiary Care Hospital in Kampala, Uganda. Preprints 2023, 2023101454. https://doi.org/10.20944/preprints202310.1454.v1

Abstract

Multidrug resistance (MDR) among gram-negative bacteria is a global public health threat because it has exhausted all standard therapeutic options. This has necessitated clinicians to reconsider colistin, an “old sort” antibiotic which was deemed toxic for clinical use. Unfortunately, swift resistance towards colistin by K. pneumoniae has been reported in different parts of the world. The study aimed at investigating the genetic determinants of colistin resistance in K. pneumoniae isolated from patients admitted in a tertiary care hospital in Kampala, Uganda. 31 archived multidrug resistant K. pneumoniae isolates obtained from rectal swabs of patients admitted to the Mulago Hospital ICU were retrieved. From this collection, we selected 7 colistin resistant K. pneumoniae isolates for whole genome sequencing and molecular profile analysis. In silico sequence data analyses were performed using established web-based bioinformatics tools. The sequence analysis of the genes involved in colistin resistance revealed several non-synonymous mutations in nucleotide sequences of pmrA, pmrB, phoP, phoQ and mgrB genes. Insertion transposase genes for the insertion sequences IS1 and IS5 which are highly implicated in colistin resistance via modification or inactivation of mgrB gene were identified in all isolates and were located in the chromosomal DNA at different genomic positions. No plasmid-borne mcr genes were detected. More so, the strains harbored numerous multidrug resistant genes. This study underscores the need of genomic surveillance of K. pneumoniae strains to limit further spread of colistin resistance genes to avert the potential risk of pandrug resistance. And high throughput sequencing is imperative.

Keywords

Klebsiella pneumoniae, whole genome sequences (WGS), antimicrobial resistance (AMR), multidrug resistance (MDR), colistin resistance

Subject

Biology and Life Sciences, Immunology and Microbiology

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