A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae

Microorganisms
Demeng TanTongyu Zhu

Abstract

Phage therapy is a potential and promising avenue for controlling the emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae, however, the rapid development of anti-phage resistance has been identified as an obstacle to the development of phage therapy. Little is known about the mechanism employed by MDR K. pneumoniae strains and how they protect themselves from lytic phage predation in vitro and in vivo. In this study, comparative genomic analysis shows undecaprenyl-phosphate glucose-1-phosphate transferase (WcaJ), the initial enzyme catalyzing the biosynthesis of colanic acid, is necessary for the adsorption of phage 117 (Podoviridae) to the host strain Kp36 to complete its lytic life cycle. In-frame deletion of wcaJ alone was sufficient to provide phage 117 resistance in the Kp36 wild-type strain. Complementation assays demonstrated the susceptibility of phage 117, and the mucoid phenotype could be restored in the resistant strain Kp36-117R by expressing the wild-type version of wcaJ. Remarkably, we found that bacterial mobile genetic elements (insA and insB) block phage 117 infections by disrupting the coding region of wcaJ, thus preventing phage adsorption to its phage receptor. Further, we revealed that t...Continue Reading

Datasets Mentioned

BETA
CP047192

Methods Mentioned

BETA
PCR
Assay

Software Mentioned

Burrows
SnpEff
Trimmomatic
MarkDuplicates
- Aligner ( BWA )
Genome Analyzer Toolkit ( GATK )
FastQC
BEDTools
SAMtools

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