Inhibition of host cell division by T5 protein 008 (Hdi)

Author:

Mahata Tridib1,Molshanski-Mor Shahar1,Goren Moran G.1,Kohen-Manor Miriam1,Yosef Ido1,Avram Oren2,Salomon Dor1ORCID,Qimron Udi1ORCID

Affiliation:

1. Department of Clinical Microbiology and Immunology, School of Medicine, Tel Aviv University, Tel Aviv, Israel

2. The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

Abstract

ABSTRACT Bacteriophages (phages) have evolved effective methods of exploiting host-cell machinery by redirecting molecular pathways. In this study, we describe an inhibitor of bacterial growth, T5.008, encoded by the T5 phage. High-throughput sequencing of genomic DNA from bacterial mutants resistant to T5.008 identified mutations in the Escherichia coli ftsZ gene, suggesting that T5.008 targets the cell division protein FtsZ. We validated this finding by replacing a residue in FtsZ with one that confers protection from T5.008 inhibition. We used time-lapse microscopy to show that T5.008 interferes with FtsZ ring formation and stability, thereby inhibiting division. We also demonstrated that phages expressing T5.008 can prevent host division before lysis much more efficiently than those lacking T5.008. We also showed that T5.008 provides a competitive advantage to the T5 phage. This strategy of inhibiting division during phage infection likely enables T5 phage to utilize host-cell resources efficiently. IMPORTANCE We have identified a novel phage-encoded inhibitor of the major cytoskeletal protein in bacterial division, FtsZ. The inhibition is shown to confer T5 bacteriophage with a growth advantage in dividing hosts. Our studies demonstrate a strategy in bacteriophages to maximize their progeny number by inhibiting escape of one of the daughter cells of an infected bacterium. They further emphasize that FtsZ is a natural target for bacterial growth inhibition.

Funder

EC | European Research Council

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

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