Essential genes from Arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines.

Proceedings of the National Academy of Sciences of the United States of America
Barry N DuplantisFrancis E Nano

Abstract

All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 degrees C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were ...Continue Reading

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Citations

Jun 1, 2011·Cellular and Molecular Life Sciences : CMLS·Matthew D WhiteFrancis E Nano
Jan 14, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Barry N DuplantisFrancis E Nano
May 15, 2012·Marine Genomics·Daniela GiordanoCinzia Verde
Apr 3, 2015·Extremophiles : Life Under Extreme Conditions·Jennifer RonholmLyle G Whyte
Apr 24, 2012·Journal of Young Pharmacists : JYP·Mm Shanmugam, S Parasuraman
Mar 1, 2012·FEMS Microbiology Letters·Cecilia Martínez-RosalesSusana Castro-Sowinski
Apr 22, 2017·Microbiology·Stephanie C PearceFrancis E Nano
Jul 19, 2015·Applied and Environmental Microbiology·Barry N DuplantisFrancis E Nano
Sep 25, 2019·Marine Drugs·Stefano BrunoCinzia Verde
Jun 27, 2019·Infection and Immunity·William G HansonPeter Lauer

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