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Title: Multicopy single-stranded DNA directs intestinal colonization of enteric pathogens

Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking its retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude thatmore » a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [4] ;  [5] ;  [5] ;  [6] ;  [4] ;  [5] ;  [7]
  1. Texas A & M Univ., College Station, TX (United States); North Carolina State Univ., Raleigh, NC (United States)
  2. Washington State Univ., Pullman, WA (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Purdue Univ., West Lafayette, IN (United States)
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  5. Texas A & M Univ., College Station, TX (United States)
  6. Univ. of California-Irvine, Irvine, CA (United States)
  7. Univ. of Washington, Seattle, WA (United States)
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
PLoS Genetics
Additional Journal Information:
Journal Volume: 11; Journal Issue: 9; Journal ID: ISSN 1553-7404
Public Library of Science
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; gastrointestinal tract; electron acceptors; salmonella; protein metabolism; nitrates; anaerobic bacteria; salmonellosis; inflammation
OSTI Identifier: