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- W2942392743 abstract "Mycobacterium tuberculosis possesses an unusually large representation of type II toxin–antitoxin (TA) systems, whose functions and targets are mostly unknown. To better understand the basis of their unique expansion and to probe putative functional similarities among these systems, here we computationally and experimentally investigated their sequence relationships. Bioinformatic and phylogenetic investigations revealed that 51 sequences of the VapBC toxin family group into paralogous sub-clusters. On the basis of conserved sequence fingerprints within paralogues, we predicted functional residues and residues at the putative TA interface that are useful to evaluate TA interactions. Substitution of these likely functional residues abolished the toxin’s growth-inhibitory activity. Furthermore, conducting similarity searches in 101 mycobacterial and ∼4500 other prokaryotic genomes, we assessed the relative conservation of the M. tuberculosis TA systems and found that most TA orthologues are well-conserved among the members of the M. tuberculosis complex, which cause tuberculosis in animal hosts. We found that soil-inhabiting, free-living Actinobacteria also harbor as many as 12 TA pairs. Finally, we identified five novel putative TA modules in M. tuberculosis. For one of them, we demonstrate that overexpression of the putative toxin, Rv2514c, induces bacteriostasis and that co-expression of the cognate antitoxin Rv2515c restores bacterial growth. Taken together, our findings reveal that toxin sequences are more closely related than antitoxin sequences in M. tuberculosis. Furthermore, the identification of additional TA systems reported here expands the known repertoire of TA systems in M. tuberculosis. Mycobacterium tuberculosis possesses an unusually large representation of type II toxin–antitoxin (TA) systems, whose functions and targets are mostly unknown. To better understand the basis of their unique expansion and to probe putative functional similarities among these systems, here we computationally and experimentally investigated their sequence relationships. Bioinformatic and phylogenetic investigations revealed that 51 sequences of the VapBC toxin family group into paralogous sub-clusters. On the basis of conserved sequence fingerprints within paralogues, we predicted functional residues and residues at the putative TA interface that are useful to evaluate TA interactions. Substitution of these likely functional residues abolished the toxin’s growth-inhibitory activity. Furthermore, conducting similarity searches in 101 mycobacterial and ∼4500 other prokaryotic genomes, we assessed the relative conservation of the M. tuberculosis TA systems and found that most TA orthologues are well-conserved among the members of the M. tuberculosis complex, which cause tuberculosis in animal hosts. We found that soil-inhabiting, free-living Actinobacteria also harbor as many as 12 TA pairs. Finally, we identified five novel putative TA modules in M. tuberculosis. For one of them, we demonstrate that overexpression of the putative toxin, Rv2514c, induces bacteriostasis and that co-expression of the cognate antitoxin Rv2515c restores bacterial growth. Taken together, our findings reveal that toxin sequences are more closely related than antitoxin sequences in M. tuberculosis. Furthermore, the identification of additional TA systems reported here expands the known repertoire of TA systems in M. tuberculosis." @default.
- W2942392743 created "2019-05-03" @default.
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- W2942392743 date "2019-06-01" @default.
- W2942392743 modified "2023-10-12" @default.
- W2942392743 title "Bioinformatic and mutational studies of related toxin–antitoxin pairs in Mycobacterium tuberculosis predict and identify key functional residues" @default.
- W2942392743 cites W1560675666 @default.
- W2942392743 cites W1604915411 @default.
- W2942392743 cites W1803102843 @default.
- W2942392743 cites W1963592098 @default.
- W2942392743 cites W1963786669 @default.
- W2942392743 cites W1965517743 @default.
- W2942392743 cites W1984774221 @default.
- W2942392743 cites W1985347638 @default.
- W2942392743 cites W1986703858 @default.
- W2942392743 cites W1990802442 @default.
- W2942392743 cites W1996357994 @default.
- W2942392743 cites W2003142446 @default.
- W2942392743 cites W2005548636 @default.
- W2942392743 cites W2008154822 @default.
- W2942392743 cites W2013903508 @default.
- W2942392743 cites W2015402183 @default.
- W2942392743 cites W2017145164 @default.
- W2942392743 cites W2023424516 @default.
- W2942392743 cites W2023490488 @default.
- W2942392743 cites W2042777786 @default.
- W2942392743 cites W2045114886 @default.
- W2942392743 cites W2047628885 @default.
- W2942392743 cites W2051584259 @default.
- W2942392743 cites W2065283382 @default.
- W2942392743 cites W2073895233 @default.
- W2942392743 cites W2090188358 @default.
- W2942392743 cites W2090486365 @default.
- W2942392743 cites W2091426267 @default.
- W2942392743 cites W2094095960 @default.
- W2942392743 cites W2097854076 @default.
- W2942392743 cites W2103222799 @default.
- W2942392743 cites W2106648157 @default.
- W2942392743 cites W2110869427 @default.
- W2942392743 cites W2114716642 @default.
- W2942392743 cites W2115463917 @default.
- W2942392743 cites W2126573196 @default.
- W2942392743 cites W2129267752 @default.
- W2942392743 cites W2130060890 @default.
- W2942392743 cites W2133711117 @default.
- W2942392743 cites W2140029549 @default.
- W2942392743 cites W2142529984 @default.
- W2942392743 cites W2144795887 @default.
- W2942392743 cites W2149292210 @default.
- W2942392743 cites W2151899778 @default.
- W2942392743 cites W2152219892 @default.
- W2942392743 cites W2153544371 @default.
- W2942392743 cites W2158714788 @default.
- W2942392743 cites W2158804744 @default.
- W2942392743 cites W2158992333 @default.
- W2942392743 cites W2163406805 @default.
- W2942392743 cites W2164814134 @default.
- W2942392743 cites W2167970541 @default.
- W2942392743 cites W2168974130 @default.
- W2942392743 cites W2170305714 @default.
- W2942392743 cites W2224056471 @default.
- W2942392743 cites W2336330109 @default.
- W2942392743 cites W2429647350 @default.
- W2942392743 cites W2431006159 @default.
- W2942392743 cites W2513670426 @default.
- W2942392743 cites W2516471498 @default.
- W2942392743 cites W2550875942 @default.
- W2942392743 cites W2570965848 @default.
- W2942392743 cites W2588841384 @default.
- W2942392743 cites W2735224236 @default.
- W2942392743 cites W2791839134 @default.
- W2942392743 cites W2900701906 @default.
- W2942392743 cites W2917698825 @default.
- W2942392743 cites W4210702584 @default.
- W2942392743 cites W4234797890 @default.
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- W2942392743 doi "https://doi.org/10.1074/jbc.ra118.006814" @default.
- W2942392743 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6556569" @default.
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- W2942392743 hasPublicationYear "2019" @default.
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