Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Klebsiella pneumoniae Clinical Strains of Hypervirulent Capsular Serotypes K1 and K2 Demonstrating Resistance against Human Serum Bactericidal Activity and Virulence in Galleria mellonella Model

Version 1 : Received: 8 January 2024 / Approved: 9 January 2024 / Online: 10 January 2024 (03:51:05 CET)

A peer-reviewed article of this Preprint also exists.

AL-Busaidi, B.; AL-Muzahmi, M.; AL-Shabibi, Z.; Rizvi, M.; AL-Rashdi, A.; AL-Jardani, A.; Farzand, R.; AL-Jabri, Z. Hypervirulent Capsular Serotypes K1 and K2 Klebsiella pneumoniae Strains Demonstrate Resistance to Serum Bactericidal Activity and Galleria mellonella Lethality. Int. J. Mol. Sci. 2024, 25, 1944. AL-Busaidi, B.; AL-Muzahmi, M.; AL-Shabibi, Z.; Rizvi, M.; AL-Rashdi, A.; AL-Jardani, A.; Farzand, R.; AL-Jabri, Z. Hypervirulent Capsular Serotypes K1 and K2 Klebsiella pneumoniae Strains Demonstrate Resistance to Serum Bactericidal Activity and Galleria mellonella Lethality. Int. J. Mol. Sci. 2024, 25, 1944.

Abstract

Hypervirulent Klebsiella pneumoniae (hvKp) is a variant that has been increasingly linked to severe, life threatening infections including pyogenic liver abscess and bloodstream infections. HvKp belonging to the capsular serotypes K1 and K2 have been reported worldwide, however very scarce studies are available on the their genomics and virulence. In the current study we report four hypermucoviscous hvKp ESBL clinical strains of capsular serotype K1 and K2 isolated from pus and urine of critically ill patients in tertiary care hospitals in Oman. These strains belong to diverse sequence types (STs) namely ST-23(K1), ST-231(K2), ST-881(K2), and ST-14(K2). To study their virulence, Galleria Mellonella model and resistance to human serum killing were used. The G. mellonella model revealed that the K1/ST-23 isolate is the most virulent as 50% of the larvae died in the first day, followed by isolate K2/ST-231 for which 75% of the larvae died in the second day and isolate K2/ST-14 for which 50% of the larvae died in the second day. Resistance to human serum killing showed there was complete inhibition of bacterial growth of all four isolates by the end of the first hour and up to the third hour. For ST-23(K1), ST-231(K2), ST-881(K2), and ST-14(K2), there was a gradual decrease in the number of colonies up to the second to third hour, which indicates neutralization of bacterial cells by the serum components. However, this was followed by sudden increase of bacterial growth, indicating possible resistance of bacteria against human serum bactericidal activity. Whole genome sequencing (WGS) revealed that hvKp strains display unique genetic arrangement of k-loci. Whole genome SNP-based phylogenetic analysis revealed that these hvKp isolates are phylogenetically distinct, belonging to diverse clades and belong to different STs in comparison to global isolates. This is the first report from Oman detailing the WGS of hvKp clinical isolates and assessing their resistance and virulence genomics, which reinforce our understanding of their epidemiology and dissemination in clinical settings.

Keywords

Hypermucoviscous1; Klebsiella pneumoniae2; Hypervirulent3; Mobile genetic elements4; capsule serotypes5; Virulence6; Whole genome sequencing7; sequence types8

Subject

Medicine and Pharmacology, Epidemiology and Infectious Diseases

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