Abstract：
:Type II (proteic) toxin-antitoxin (TA) operons are widely spread in bacteria and archaea. They are organized as operons in which, usually, the antitoxin gene precedes the cognate toxin gene. The antitoxin generally acts as a transcriptional self-repressor, whereas the toxin acts as a co-repressor, both proteins constituting a harmless complex. When bacteria encounter a stressful environment, TAs are triggered. The antitoxin protein is unstable and will be degraded by host proteases, releasing the free toxin to halt essential processes. The result is a cessation of cell growth or even death. Because of their ubiquity and the essential processes targeted, TAs have been proposed as good candidates for development of novel antimicrobials. We discuss here the possible druggability of TAs as antivirals and antibacterials, with focus on the potentials and the challenges that their use may find in the 'real' world. We present strategies to develop TAs as antibacterials in view of novel technologies, such as the use of very small molecules (fragments) as inhibitors of protein-protein interactions. Appropriate fragments could disrupt the T:A interfaces leading to the release of the targeted TA pair. Possible ways of delivery and formulation of Tas are also discussed.
journal_name
FEMS Microbiol Revjournal_title
FEMS microbiology reviewsauthors
Chan WT,Balsa D,Espinosa Mdoi
10.1093/femsre/fuv002subject
Has Abstractpub_date
2015-07-01 00:00:00pages
522-40issue
4eissn
0168-6445issn
1574-6976pii
fuv002journal_volume
39pub_type
杂志文章,评审abstract：:Most bacteria pathogenic for humans have closely related nonpathogenic counterparts that live as saprophytes, commensals or even symbionts (mutualists) in similar or different habitats. The knowledge of how these bacteria adapt their metabolism to the preferred habitats is critical for our understanding of pathogenesi...
journal_title：FEMS microbiology reviews
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journal_title：FEMS microbiology reviews
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journal_title：FEMS microbiology reviews
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pub_type： 杂志文章,评审
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journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
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更新日期：2001-12-01 00:00:00
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journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
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pub_type： 杂志文章,评审
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journal_title：FEMS microbiology reviews
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pub_type： 杂志文章,评审
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更新日期：2012-05-01 00:00:00
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更新日期：2018-09-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2018-05-01 00:00:00
abstract：:The successful genetic manipulation of Clostridium acetobutylicum for the increased production of solvents will depend on an understanding of gene structure and regulation in the bacterium. The glutamine synthetase (glnA) gene is regulated by antisense RNA, transcribed from a downstream promoter, in the opposite direc...
journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
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更新日期：1995-10-01 00:00:00
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journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
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更新日期：1998-09-01 00:00:00
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journal_title：FEMS microbiology reviews
pub_type： 杂志文章
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更新日期：1994-08-01 00:00:00
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journal_title：FEMS microbiology reviews
pub_type： 杂志文章,评审
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更新日期：2007-09-01 00:00:00
