A competence-regulated toxin-antitoxin system in Haemophilus influenzae

Autoři: Hailey Findlay Black aff001;  Scott Mastromatteo aff001;  Sunita Sinha aff002;  Rachel L. Ehrlich aff003;  Corey Nislow aff004;  Joshua Chang Mell aff003;  Rosemary J. Redfield aff001
Působiště autorů: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada aff001;  Sequencing + Bioinformatics Consortium, Office of the Vice-President, University of British Columbia, Vancouver, British Columbia, Canada aff002;  Department of Microbiology & Immunology, Center for Genomic Sciences, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America aff003;  Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0217255


Natural competence allows bacteria to respond to environmental and nutritional cues by taking up free DNA from their surroundings, thus gaining both nutrients and genetic information. In the Gram-negative bacterium Haemophilus influenzae, the genes needed for DNA uptake are induced by the CRP and Sxy transcription factors in response to lack of preferred carbon sources and nucleotide precursors. Here we show that one of these genes, HI0659, encodes the antitoxin of a competence-regulated toxin-antitoxin operon (‘toxTA’), likely acquired by horizontal gene transfer from a Streptococcus species. Deletion of the putative toxin (HI0660) restores uptake to the antitoxin mutant. The full toxTA operon was present in only 17 of the 181 strains we examined; complete deletion was seen in 22 strains and deletions removing parts of the toxin gene in 142 others. In addition to the expected Sxy- and CRP-dependent-competence promoter, HI0659/660 transcript analysis using RNA-seq identified an internal antitoxin-repressed promoter whose transcription starts within toxT and will yield nonfunctional protein. We propose that the most likely effect of unopposed toxin expression is non-specific cleavage of mRNAs and arrest or death of competent cells in the culture. Although the high frequency of toxT and toxTA deletions suggests that this competence-regulated toxin-antitoxin system may be mildly deleterious, it could also facilitate downregulation of protein synthesis and recycling of nucleotides under starvation conditions. Although our analyses were focused on the effects of toxTA, the RNA-seq dataset will be a useful resource for further investigations into competence regulation.

Klíčová slova:

Antitoxins – DNA – Gene regulation – Haemophilus influenzae – Operons – RNA analysis – Sequence alignment – Toxins


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