Abundance of type I toxin-antitoxin systems in bacteria: searches for new candidates and discovery of novel families.
Small, hydrophobic proteins whose synthesis is repressed by small RNAs (sRNAs), denoted type I toxin-antitoxin modules, were first discovered on plasmids where they regulate plasmid stability, but were subsequently found on a few bacterial chromosomes. We used exhaustive PSI-BLAST and TBLASTN searches across 774 bacterial genomes to identify homologs of known type I toxins. These searches substantially expanded the collection of predicted type I toxins, revealed homology of the Ldr and Fst toxins, and suggested that type I toxin-antitoxin loci are not spread by horizontal gene transfer. To discover novel type I toxin-antitoxin systems, we developed a set of search parameters based on characteristics of known loci including the presence of tandem repeats and clusters of charged and bulky amino acids at the C-termini of short proteins containing predicted transmembrane regions. We detected sRNAs for three predicted toxins from enterohemorrhagic Escherichia coli and Bacillus subtilis, and showed that two of the respective proteins indeed are toxic when overexpressed. We also demonstrated that the local free-energy minima of RNA folding can be used to detect the positions of the sRNA genes. Our results suggest that type I toxin-antitoxin modules are much more widely distributed among bacteria than previously appreciated.
Fozo
Elizabeth M
EM
Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA.
Makarova
Kira S
KS
Shabalina
Svetlana A
SA
Yutin
Natalya
N
Koonin
Eugene V
EV
Storz
Gisela
G
D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D001427:Bacterial Toxins / Q000145:classification / Q000235:genetics*; D013293:Enterococcus faecalis / Q000235:genetics; D019453:Escherichia coli O157 / Q000235:genetics; D016680:Genome, Bacterial; D023281:Genomics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics*; D012329:RNA, Bacterial / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D022661:RNA, Untranslated / Q000737:chemistry / Q000145:classification / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000235:genetics; D020080:Tandem Repeat Sequences; D013816:Thermodynamics
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D016372:RNA, Antisense; D012329:RNA, Bacterial; D022661:RNA, Untranslated