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PMID: 22300632 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A vast collection of microbial genes that are toxic to bacteria.

Genome research ·Vol. 22 ·No. 4 ·2012-04-00 ·Pages 802-9

Kimelman A, Levy A, Sberro H, Kidron S, Leavitt A, Amitai G, Yoder-Himes DR, Wurtzel O, Zhu Y, Rubin EM, Sorek R

Abstract

In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non-coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions.

MeSH Terms
Anti-Bacterial Agents/metabolism,pharmacology Bacterial Proteins/genetics,metabolism Base Sequence Binding Sites/genetics Cloning, Molecular DNA, Bacterial/genetics,metabolism,pharmacology DNA-Binding Proteins/genetics,metabolism Escherichia coli/genetics,metabolism Gene Expression Regulation, Bacterial Genes, Bacterial/genetics Genome, Bacterial/genetics Microbial Viability/drug effects,genetics Molecular Sequence Data Protein Binding RNA, Bacterial/genetics,metabolism,pharmacology RNA, Transfer/genetics,metabolism,pharmacology Sequence Homology, Nucleic Acid Transcription, Genetic
Chemicals
Anti-Bacterial Agents Bacterial Proteins DNA, Bacterial DNA-Binding Proteins DnaA protein, Bacteria RNA, Bacterial RNA, Transfer
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Kimelman Aya
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Levy Asaf
Sberro Hila
Kidron Shahar
Leavitt Azita
Amitai Gil
Yoder-Himes Deborah R
Wurtzel Omri
Zhu Yiwen
Rubin Edward M
Sorek Rotem
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1549-5469
DOI
10.1101/gr.133850.111
Published
2012-04-00
Epub
2012-00-01
Pages
802-9
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC3317161
Subset
IM
Grants
NIAID NIH HHS · R01 AI082376 · United States
NIAID NIH HHS · NIH R01AI082376-01 · United States
Databases
GENBANK
JQ317270, JQ317271, JQ317272, JQ317273, JQ317274, JQ323150, JQ323151, JQ323152
Corrections
CommentIn
PMID: 22705841
External Links
PubMed source DOI: 10.1101/gr.133850.111 PMC Full Text View journal details
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