Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways

Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation and/or by directly mediating cell death, all through the toxin activity upon degradation of antitoxin. Intensive study has revealed specific...

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Published inToxins Vol. 8; no. 7; p. 214
Main Authors Muthuramalingam, Meenakumari, White, John C, Bourne, Christina R
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 09.07.2016
MDPI AG
Subjects
Animals
Anti-Bacterial Agents - pharmacology
Antitoxins - metabolism
Bacteria - drug effects
Bacteria - enzymology
Bacteria - growth & development
Bacteria - pathogenicity
bacterial physiology
Bacterial Toxins - metabolism
cellular proteases
Endopeptidase Clp - metabolism
environmental adaptation
Enzyme Activation
Host-Pathogen Interactions
Humans
persister cells
phenotypic changes
post-segregational killing
protease adaptors
Protease La - metabolism
Proteolysis
Review
Signal Transduction - drug effects
toxin-antitoxin
bacterial physiology
cellular proteases
phenotypic changes
post-segregational killing
toxin-antitoxin
environmental adaptation
protease adaptors
persister cells
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Abstract Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation and/or by directly mediating cell death, all through the toxin activity upon degradation of antitoxin. Intensive study has revealed specific details of TA module functions, but significant gaps remain about the molecular details of activation via antitoxin degradation used by different bacteria and in different environments. This review summarizes the current state of knowledge about the interaction of antitoxins with cellular proteases Lon and ClpP to mediate TA module activation. An understanding of these processes can answer long-standing questions regarding stochastic versus specific activation of TA modules and provide insight into the potential for manipulation of TA modules to alter bacterial growth.
AbstractList Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation and/or by directly mediating cell death, all through the toxin activity upon degradation of antitoxin. Intensive study has revealed specific details of TA module functions, but significant gaps remain about the molecular details of activation via antitoxin degradation used by different bacteria and in different environments. This review summarizes the current state of knowledge about the interaction of antitoxins with cellular proteases Lon and ClpP to mediate TA module activation. An understanding of these processes can answer long-standing questions regarding stochastic versus specific activation of TA modules and provide insight into the potential for manipulation of TA modules to alter bacterial growth.
Author Muthuramalingam, Meenakumari
Bourne, Christina R
White, John C
AuthorAffiliation Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA; meena85@ou.edu (M.M.); John.C.White-1@ou.edu (J.C.W.)
AuthorAffiliation_xml – name: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA; meena85@ou.edu (M.M.); John.C.White-1@ou.edu (J.C.W.)
Author_xml – sequence: 1
  givenname: Meenakumari
  surname: Muthuramalingam
  fullname: Muthuramalingam, Meenakumari
  email: meena85@ou.edu
  organization: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA. meena85@ou.edu
– sequence: 2
  givenname: John C
  surname: White
  fullname: White, John C
  email: John.C.White-1@ou.edu
  organization: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA. John.C.White-1@ou.edu
– sequence: 3
  givenname: Christina R
  surname: Bourne
  fullname: Bourne, Christina R
  email: cbourne@ou.edu
  organization: Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA. cbourne@ou.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27409636$$D View this record in MEDLINE/PubMed
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Issue 7
Keywords bacterial physiology
cellular proteases
phenotypic changes
post-segregational killing
toxin-antitoxin
environmental adaptation
protease adaptors
persister cells
Language English
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Snippet Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation...
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StartPage 214
SubjectTerms Animals
Anti-Bacterial Agents - pharmacology
Antitoxins - metabolism
Bacteria - drug effects
Bacteria - enzymology
Bacteria - growth & development
Bacteria - pathogenicity
bacterial physiology
Bacterial Toxins - metabolism
cellular proteases
Endopeptidase Clp - metabolism
environmental adaptation
Enzyme Activation
Host-Pathogen Interactions
Humans
persister cells
phenotypic changes
post-segregational killing
protease adaptors
Protease La - metabolism
Proteolysis
Review
Signal Transduction - drug effects
toxin-antitoxin
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Title Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways
URI https://www.ncbi.nlm.nih.gov/pubmed/27409636
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https://pubmed.ncbi.nlm.nih.gov/PMC4963847
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