HmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe

Typeset version

 

TY  - JOUR
  - Heuston, S,Begley, M,Davey, MS,Eberl, M,Casey, PG,Hill, C,Gahan, CGM
  - 2012
  - January
  - Microbiology-SGM
  - HmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe
  - Validated
  - ()
  - 2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE PATHWAY DELTA-T-CELLS ESCHERICHIA-COLI MYCOBACTERIUM-TUBERCULOSIS VIRULENCE DETERMINANTS NONMEVALONATE PATHWAY LACTOCOCCUS-LACTIS LYTB GENE IDENTIFICATION ACTIVATION
  - 158
  - 1684
  - 1693
  - Isoprenoids may be synthesized via one of two pathways, the classical mevalonate pathway or the alternative 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. While the majority of bacteria utilize a single pathway for isoprenoid biosynthesis, Listeria monocytogenes is unusual in possessing the complete set of genes for both pathways. Here, we utilized new molecular tools to create precise gene deletions in selected genes encoding enzymes of both pathways, gcpE, lytB (encoding proteins in the MEP pathway) and hmgR (encoding a protein in the mevalonate pathway). We demonstrate that the hmgR gene can only be deleted when the growth medium is supplemented with exogenous mevalonate. Furthermore, full growth of the mutant in the absence of mevalonate was only possible when the intact hmgR gene was supplied in trans using an IPTG-inducible expression system. Murine competitive index assays performed via the oral and intraperitoneal routes of infection revealed that the mevalonate hmgR mutant could not be recovered from livers and spleens 3 days post-infection. We propose that HmgR in L. monocytogenes EGDe is involved in essential metabolic functions and that an intact MEP pathway is not capable of sustaining growth.
  - DOI 10.1099/mic.0.056069-0
DA  - 2012/01
ER  - 
@article{V190496392,
   = {Heuston,  S and Begley,  M and Davey,  MS and Eberl,  M and Casey,  PG and Hill,  C and Gahan,  CGM },
   = {2012},
   = {January},
   = {Microbiology-SGM},
   = {HmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe},
   = {Validated},
   = {()},
   = {2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE PATHWAY DELTA-T-CELLS ESCHERICHIA-COLI MYCOBACTERIUM-TUBERCULOSIS VIRULENCE DETERMINANTS NONMEVALONATE PATHWAY LACTOCOCCUS-LACTIS LYTB GENE IDENTIFICATION ACTIVATION},
   = {158},
  pages = {1684--1693},
   = {{Isoprenoids may be synthesized via one of two pathways, the classical mevalonate pathway or the alternative 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. While the majority of bacteria utilize a single pathway for isoprenoid biosynthesis, Listeria monocytogenes is unusual in possessing the complete set of genes for both pathways. Here, we utilized new molecular tools to create precise gene deletions in selected genes encoding enzymes of both pathways, gcpE, lytB (encoding proteins in the MEP pathway) and hmgR (encoding a protein in the mevalonate pathway). We demonstrate that the hmgR gene can only be deleted when the growth medium is supplemented with exogenous mevalonate. Furthermore, full growth of the mutant in the absence of mevalonate was only possible when the intact hmgR gene was supplied in trans using an IPTG-inducible expression system. Murine competitive index assays performed via the oral and intraperitoneal routes of infection revealed that the mevalonate hmgR mutant could not be recovered from livers and spleens 3 days post-infection. We propose that HmgR in L. monocytogenes EGDe is involved in essential metabolic functions and that an intact MEP pathway is not capable of sustaining growth.}},
   = {DOI 10.1099/mic.0.056069-0},
  source = {IRIS}
}
AUTHORSHeuston, S,Begley, M,Davey, MS,Eberl, M,Casey, PG,Hill, C,Gahan, CGM
YEAR2012
MONTHJanuary
JOURNAL_CODEMicrobiology-SGM
TITLEHmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe
STATUSValidated
TIMES_CITED()
SEARCH_KEYWORD2-C-METHYL-D-ERYTHRITOL 4-PHOSPHATE PATHWAY DELTA-T-CELLS ESCHERICHIA-COLI MYCOBACTERIUM-TUBERCULOSIS VIRULENCE DETERMINANTS NONMEVALONATE PATHWAY LACTOCOCCUS-LACTIS LYTB GENE IDENTIFICATION ACTIVATION
VOLUME158
ISSUE
START_PAGE1684
END_PAGE1693
ABSTRACTIsoprenoids may be synthesized via one of two pathways, the classical mevalonate pathway or the alternative 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. While the majority of bacteria utilize a single pathway for isoprenoid biosynthesis, Listeria monocytogenes is unusual in possessing the complete set of genes for both pathways. Here, we utilized new molecular tools to create precise gene deletions in selected genes encoding enzymes of both pathways, gcpE, lytB (encoding proteins in the MEP pathway) and hmgR (encoding a protein in the mevalonate pathway). We demonstrate that the hmgR gene can only be deleted when the growth medium is supplemented with exogenous mevalonate. Furthermore, full growth of the mutant in the absence of mevalonate was only possible when the intact hmgR gene was supplied in trans using an IPTG-inducible expression system. Murine competitive index assays performed via the oral and intraperitoneal routes of infection revealed that the mevalonate hmgR mutant could not be recovered from livers and spleens 3 days post-infection. We propose that HmgR in L. monocytogenes EGDe is involved in essential metabolic functions and that an intact MEP pathway is not capable of sustaining growth.
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DOI_LINKDOI 10.1099/mic.0.056069-0
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