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

Eddie B Gilcrease; Sherwood R Casjens; Ananda Bhattacharjee; Ramesh Goel

doi:10.3389/fmicb.2023.1100607

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

Front Microbiol. 2023 Feb 17:14:1100607. doi: 10.3389/fmicb.2023.1100607. eCollection 2023.

Authors

Eddie B Gilcrease¹, Sherwood R Casjens^{2

3}, Ananda Bhattacharjee⁴, Ramesh Goel¹

Affiliations

¹ Department of Civil and Environmental Engineering, University of Utah, Salt Lake City, UT, United States.
² School of Biological Sciences, University of Utah, Salt Lake City, UT, United States.
³ Division of Microbiology and Immunology, Pathology Department, University of Utah, Salt Lake City, UT, United States.
⁴ Department of Environmental Sciences, University of California, Riverside, CA, United States.

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. GRAPHICAL ABSTRACT.

Keywords: Klebsiella pneumoniae; NDM-1; antibiotic resistance; lytic phage; polyvalency.