A Klebsiella pneumoniae NDM-1+ bacteriophage: Adaptive polyvalence and disruption of heterogenous biofilms

Abstract

Bacteriophage KL-2146 is a lytic virus isolated to infect Klebsiella pneumoniae BAA2146, a pathogen carrying the broad range antibiotic resistance gene New Delhi metallo-betalactamase-1 (NDM-1). Upon complete characterization, the virus is shown to belong to the Drexlerviridae family and is a member of the Webervirus genus located within the (formerly) T1-like cluster of phages. Its double-stranded (dsDNA) genome is 47,844 bp long and is predicted to have 74 protein-coding sequences (CDS). After challenging a variety of K. pneumoniae strains with phage KL-2146, grown on the NDM-1 positive strain BAA-2146, polyvalence was shown for a single antibiotic-sensitive strain, K. pneumoniae 13,883, with a very low initial infection efficiency in liquid culture. However, after one or more cycles of infection in K. pneumoniae 13,883, nearly 100% infection efficiency was achieved, while infection efficiency toward its original host, K. pneumoniae BAA-2146, was decreased. This change in host specificity is reversible upon re-infection of the NDM-1 positive strain (BAA-2146) using phages grown on the NDM-1 negative strain (13883). In biofilm infectivity experiments, the polyvalent nature of KL-2146 was demonstrated with the killing of both the multidrug-resistant K. pneumoniae BAA-2146 and drug-sensitive 13,883 in a multi-strain biofilm. The ability to infect an alternate, antibiotic-sensitive strain makes KL-2146 a useful model for studying phages infecting the NDM-1+ strain, K. pneumoniae BAA-2146.

Relationship between biofilm formation and antibiotic resistance of Klebsiella pneumoniae and updates on antibiofilm therapeutic strategies

“…Phage vB_Kpn_ZCKp20p isolated from urban and medical sewage showed the ability to lyse biofilm-producing MDR K. pneumoniae isolates without cytotoxicity to human skin fibroblasts, and could inhibit biofilm formation and disrupt mature biofilms (Zaki et al, 2023). Polyvalent phage KL-2146 can infect NDM producing Klebsiella and antibiotic-sensitive K. pneumoniae 13, 883, which was demonstrated to effectively disrupt biofilms possessing multiple Klebsiella strains (Gilcrease et al, 2023). Asif et al isolated a K-17 serotype specific K. pneumoniae phage JKP2, which could significantly eliminate preformed biofilms with a rate of 98% for 24-hour-old biofilm, 96% of 48-hour-old biofilm, 86% and 82% for mature biofilm on day 3 and 4, respectively (Asif et al, 2023).…”