Toxin–antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes

By D. Pandey, Kenn Gerdes. Nucleic Acids Research, 2005

959 citations recorded by the source corpus.

Prokaryotic chromosomes code for toxin–antitoxin (TA) loci, often in multiple copies. In E.coli, experimental evidence indicates that TA loci are stress-response elements that help cells survive unfavorable growth conditions. The first gene in a TA operon codes for an antitoxin that combines with and neutralizes a regulatory ‘toxin’, encoded by the second gene. RelE and MazF toxins are regulators of translation that cleave mRNA and function, in interplay with tmRNA, in quality control of gene expression. Here, we present the results from an exhaustive search for TA loci in 126 completely sequenced prokaryotic genomes (16 archaea and 110 bacteria). We identified 671 TA loci belonging to the seven known TA gene families. Surprisingly, obligate intracellular organisms were devoid of TA loci, whereas free-living slowly growing prokaryotes had particularly many (38 in Mycobacterium tuberculosis and 43 in Nitrosomonas europaea). In many cases, TA loci were clustered and closely linked to mobile genetic elements. In the most extreme of these cases, all 13 TA loci of Vibrio cholerae were bona fide integron elements located in the V.cholerae mega-integron. These observations strongly suggest that TA loci are mobile cassettes that move frequently within and between chromosomes and also lend support to the hypothesis that TA loci function as stress-response elements beneficial to free-living prokaryotes.

Subfields: Endocrinology, Genetics, Molecular Medicine

View Paper: https://www.semanticscholar.org/paper/f927812cda96d8316cb67d276d42c0ea503a5c83

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Citations in the corpus

Toward rationally redesigning bacterial two-component signaling systems using coevolutionary information (2014, background): “Our methodology also potentially forms a starting foundation for the system-level study of protein–protein interactions in TCS systems as well as other signaling systems and regulatory proteins, such as the toxin–antitoxin (TA) proteins (50), provided that there are enough sequences of interacting p”
Persisters: a distinct physiological state of E. coli (2006, background): “tuberculosis that forms a dormant, persistent carrier state is >60 [31,32].”
Toxin-antitoxin systems in bacteria and archaea. (2011, background): “This toxin may inhibit cell growth by targeting a key molecule in any one of several essential cellular processes, including DNA replication, mRNA stability, protein synthesis, cell-wall biosynthesis, and ATP synthesis (88, 97).”
Integrons: agents of bacterial evolution (2006, background): “Of particular interest is the discovery that superintegrons carry several gene cassettes encoding members of different toxin–antitoxin families found in low-copy-number plasmid”
Ciprofloxacin Causes Persister Formation by Inducing the TisB toxin in Escherichia coli (2010, background): “coli, there are at least 15 TA modules [20,22,23].”
Mechanisms of bacterial persistence during stress and antibiotic exposure (2016, neutral): “tuberculosis, and Salmonella enterica serovar Typhimurium (106).”
Antibiotic resistance and persistence—Implications for human health and treatment perspectives (2020, positive): “In the largest and best studied group of TA modules, the type II TA systems, antitoxins are proteins that directly bind their cognate toxins thereby neutralizing the toxin (Pandey & Gerdes, 2005).”