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A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae
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 mec...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142929/ https://www.ncbi.nlm.nih.gov/pubmed/32156053 http://dx.doi.org/10.3390/microorganisms8030378 |
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author | Tan, Demeng Zhang, Yiyuan Qin, Jinhong Le, Shuai Gu, Jingmin Chen, Li-kuang Guo, Xiaokui Zhu, Tongyu |
author_facet | Tan, Demeng Zhang, Yiyuan Qin, Jinhong Le, Shuai Gu, Jingmin Chen, Li-kuang Guo, Xiaokui Zhu, Tongyu |
author_sort | Tan, Demeng |
collection | PubMed |
description | 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 the wcaJ mutation likely occurred spontaneously rather than adapted by phage 117 predation under unfavorable environments. Taken together, our results address a crucial evolutionary question around the mechanisms of phage–host interactions, increasing our current understandings of anti-phage defense mechanisms in this important MDR pathogen. |
format | Online Article Text |
id | pubmed-7142929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71429292020-04-14 A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae Tan, Demeng Zhang, Yiyuan Qin, Jinhong Le, Shuai Gu, Jingmin Chen, Li-kuang Guo, Xiaokui Zhu, Tongyu Microorganisms Article 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 the wcaJ mutation likely occurred spontaneously rather than adapted by phage 117 predation under unfavorable environments. Taken together, our results address a crucial evolutionary question around the mechanisms of phage–host interactions, increasing our current understandings of anti-phage defense mechanisms in this important MDR pathogen. MDPI 2020-03-07 /pmc/articles/PMC7142929/ /pubmed/32156053 http://dx.doi.org/10.3390/microorganisms8030378 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tan, Demeng Zhang, Yiyuan Qin, Jinhong Le, Shuai Gu, Jingmin Chen, Li-kuang Guo, Xiaokui Zhu, Tongyu A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae |
title | A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae |
title_full | A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae |
title_fullStr | A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae |
title_full_unstemmed | A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae |
title_short | A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae |
title_sort | frameshift mutation in wcaj associated with phage resistance in klebsiella pneumoniae |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142929/ https://www.ncbi.nlm.nih.gov/pubmed/32156053 http://dx.doi.org/10.3390/microorganisms8030378 |
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