Insights into Lantibiotic Immunity Provided by Bioengineering of LtnI

Typeset version

 

TY  - JOUR
  - Draper, LA,Deegan, LH,Hill, C,Cotter, PD,Ross, RP
  - 2012
  - January
  - Antimicrobial Agents and Chemotherapy
  - Insights into Lantibiotic Immunity Provided by Bioengineering of LtnI
  - Validated
  - ()
  - RESISTANT STAPHYLOCOCCUS-AUREUS BIOSYNTHETIC GENE-CLUSTER MEMBRANE-PROTEIN TOPOLOGY HOST BACILLUS-SUBTILIS FUNCTIONAL-ANALYSIS LACTOCOCCUS-LACTIS SELF-PROTECTION MOLECULAR ANALYSIS CONFERS IMMUNITY WARNERI ISK-1
  - 56
  - 5122
  - 5133
  - The lantibiotic lacticin 3147 has been the focus of much research due to its broad spectrum of activity against many microbial targets, including drug-resistant pathogens. In order to protect itself, a lacticin 3147 producer must possess a cognate immunity mechanism. Lacticin 3147 immunity is provided by an ABC transporter, LtnFE, and a dedicated immunity protein, LtnI, both of which are capable of independently providing a degree of protection. In the study described here, we carried out an in-depth investigation of LtnI structure-function relationships through the creation of a series of fusion proteins and LtnI determinants that have been the subject of random and site-directed mutagenesis. We establish that LtnI is a transmembrane protein that contains a number of individual residues and regions, such as those between amino acids 20 and 27 and amino acids 76 and 83, which are essential for LtnI function. Finally, as a consequence of the screening of a bank of 28,000 strains producing different LtnI derivatives, we identified one variant (LtnI I81V) that provides enhanced protection. To our knowledge, this is the first report of a lantibiotic immunity protein with enhanced functionality.
  - DOI 10.1128/AAC.00979-12
DA  - 2012/01
ER  - 
@article{V190496316,
   = {Draper,  LA and Deegan,  LH and Hill,  C and Cotter,  PD and Ross,  RP },
   = {2012},
   = {January},
   = {Antimicrobial Agents and Chemotherapy},
   = {Insights into Lantibiotic Immunity Provided by Bioengineering of LtnI},
   = {Validated},
   = {()},
   = {RESISTANT STAPHYLOCOCCUS-AUREUS BIOSYNTHETIC GENE-CLUSTER MEMBRANE-PROTEIN TOPOLOGY HOST BACILLUS-SUBTILIS FUNCTIONAL-ANALYSIS LACTOCOCCUS-LACTIS SELF-PROTECTION MOLECULAR ANALYSIS CONFERS IMMUNITY WARNERI ISK-1},
   = {56},
  pages = {5122--5133},
   = {{The lantibiotic lacticin 3147 has been the focus of much research due to its broad spectrum of activity against many microbial targets, including drug-resistant pathogens. In order to protect itself, a lacticin 3147 producer must possess a cognate immunity mechanism. Lacticin 3147 immunity is provided by an ABC transporter, LtnFE, and a dedicated immunity protein, LtnI, both of which are capable of independently providing a degree of protection. In the study described here, we carried out an in-depth investigation of LtnI structure-function relationships through the creation of a series of fusion proteins and LtnI determinants that have been the subject of random and site-directed mutagenesis. We establish that LtnI is a transmembrane protein that contains a number of individual residues and regions, such as those between amino acids 20 and 27 and amino acids 76 and 83, which are essential for LtnI function. Finally, as a consequence of the screening of a bank of 28,000 strains producing different LtnI derivatives, we identified one variant (LtnI I81V) that provides enhanced protection. To our knowledge, this is the first report of a lantibiotic immunity protein with enhanced functionality.}},
   = {DOI 10.1128/AAC.00979-12},
  source = {IRIS}
}
AUTHORSDraper, LA,Deegan, LH,Hill, C,Cotter, PD,Ross, RP
YEAR2012
MONTHJanuary
JOURNAL_CODEAntimicrobial Agents and Chemotherapy
TITLEInsights into Lantibiotic Immunity Provided by Bioengineering of LtnI
STATUSValidated
TIMES_CITED()
SEARCH_KEYWORDRESISTANT STAPHYLOCOCCUS-AUREUS BIOSYNTHETIC GENE-CLUSTER MEMBRANE-PROTEIN TOPOLOGY HOST BACILLUS-SUBTILIS FUNCTIONAL-ANALYSIS LACTOCOCCUS-LACTIS SELF-PROTECTION MOLECULAR ANALYSIS CONFERS IMMUNITY WARNERI ISK-1
VOLUME56
ISSUE
START_PAGE5122
END_PAGE5133
ABSTRACTThe lantibiotic lacticin 3147 has been the focus of much research due to its broad spectrum of activity against many microbial targets, including drug-resistant pathogens. In order to protect itself, a lacticin 3147 producer must possess a cognate immunity mechanism. Lacticin 3147 immunity is provided by an ABC transporter, LtnFE, and a dedicated immunity protein, LtnI, both of which are capable of independently providing a degree of protection. In the study described here, we carried out an in-depth investigation of LtnI structure-function relationships through the creation of a series of fusion proteins and LtnI determinants that have been the subject of random and site-directed mutagenesis. We establish that LtnI is a transmembrane protein that contains a number of individual residues and regions, such as those between amino acids 20 and 27 and amino acids 76 and 83, which are essential for LtnI function. Finally, as a consequence of the screening of a bank of 28,000 strains producing different LtnI derivatives, we identified one variant (LtnI I81V) that provides enhanced protection. To our knowledge, this is the first report of a lantibiotic immunity protein with enhanced functionality.
PUBLISHER_LOCATION
ISBN_ISSN
EDITION
URL
DOI_LINKDOI 10.1128/AAC.00979-12
FUNDING_BODY
GRANT_DETAILS