PMID- 16238626
OWN - NLM
STAT- MEDLINE
DCOM- 20060105
LR  - 20211203
IS  - 0950-382X (Print)
IS  - 0950-382X (Linking)
VI  - 58
IP  - 3
DP  - 2005 Nov
TI  - Overexpression of Mycobacterium tuberculosis manB, a phosphomannomutase that 
      increases phosphatidylinositol mannoside biosynthesis in Mycobacterium smegmatis 
      and mycobacterial association with human macrophages.
PG  - 774-90
AB  - Mycobacterium tuberculosis (M. tb) pathogenesis involves the interaction between 
      the mycobacterial cell envelope and host macrophage, a process mediated, in part, 
      by binding of the mannose caps of M. tb lipoarabinomannan (ManLAM) to the 
      macrophage mannose receptor (MR). A presumed critical step in the biosynthesis of 
      ManLAM, and other mannose-containing glycoconjugates, is the conversion of 
      mannose-6-phosphate to mannose-1-phosphate, by a phosphomannomutase (PMM), to 
      produce GDP-mannose, the primary mannose-donor in mycobacteria. We have 
      identified four M. tb H37Rv genes with similarity to known PMMs. Using in vivo 
      complementation of PMM and phosphoglucomutase (PGM) deficient strains of 
      Pseudomonas aeruginosa, and an in vitro enzyme assay, we have identified both PMM 
      and PGM activity from one of these genes, Rv3257c (MtmanB). MtmanB overexpression 
      in M. smegmatis produced increased levels of LAM, lipomannan, and 
      phosphatidylinositol mannosides (PIMs) compared with control strains and led to a 
      13.3 +/- 3.9-fold greater association of mycobacteria with human macrophages, in 
      a mannan-inhibitable fashion. This increased association was mediated by the 
      overproduction of higher order PIMs that possess mannose cap structures. We 
      conclude that MtmanB encodes a functional PMM involved in the biosynthesis of 
      mannosylated lipoglycans that participate in the association of mycobacteria with 
      macrophage phagocytic receptors.
FAU - McCarthy, Travis R
AU  - McCarthy TR
AD  - Department of Medicine and Molecular Virology, the Center for Microbial Interface 
      Biology, and the Division of Infectious Diseases, The Ohio State University, 
      Columbus, OH 43210, USA.
FAU - Torrelles, Jordi B
AU  - Torrelles JB
FAU - MacFarlane, Amanda Shearer
AU  - MacFarlane AS
FAU - Katawczik, Melanie
AU  - Katawczik M
FAU - Kutzbach, Beth
AU  - Kutzbach B
FAU - Desjardin, Lucy E
AU  - Desjardin LE
FAU - Clegg, Steven
AU  - Clegg S
FAU - Goldberg, Joanna B
AU  - Goldberg JB
FAU - Schlesinger, Larry S
AU  - Schlesinger LS
LA  - eng
GR  - AI052458/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Microbiol
JT  - Molecular microbiology
JID - 8712028
RN  - 0 (Bacterial Proteins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Mannose Receptor)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (lipoarabinomannan)
RN  - 0 (lipomannan)
RN  - 0 (phosphatidylinositol mannoside)
RN  - EC 2.7.7.- (ManB protein, bacteria)
RN  - EC 2.7.7.- (Nucleotidyltransferases)
RN  - EC 5.3.1.8 (Mannose-6-Phosphate Isomerase)
RN  - EC 5.4.2.- (Phosphotransferases (Phosphomutases))
RN  - EC 5.4.2.8 (phosphomannomutase)
SB  - IM
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Carbohydrate Conformation
MH  - Carbohydrate Sequence
MH  - Cell Wall/chemistry
MH  - Gene Expression Regulation, Bacterial
MH  - Genetic Complementation Test
MH  - Humans
MH  - Lectins, C-Type/metabolism
MH  - Lipopolysaccharides/chemistry/metabolism
MH  - Macrophages/metabolism/*microbiology
MH  - Mannose Receptor
MH  - Mannose-6-Phosphate Isomerase/genetics/*metabolism
MH  - Mannose-Binding Lectins/metabolism
MH  - Molecular Sequence Data
MH  - Molecular Structure
MH  - Multienzyme Complexes/genetics/*metabolism
MH  - Mycobacterium smegmatis/cytology/genetics/*metabolism
MH  - Mycobacterium tuberculosis/*enzymology/genetics
MH  - Nucleotidyltransferases/genetics/*metabolism
MH  - Open Reading Frames
MH  - Phosphatidylinositols/*biosynthesis/chemistry
MH  - Phosphotransferases (Phosphomutases)/genetics/*metabolism
MH  - Pseudomonas aeruginosa/genetics/metabolism
MH  - Receptors, Cell Surface/metabolism
EDAT- 2005/10/22 09:00
MHDA- 2006/01/06 09:00
CRDT- 2005/10/22 09:00
PHST- 2005/10/22 09:00 [pubmed]
PHST- 2006/01/06 09:00 [medline]
PHST- 2005/10/22 09:00 [entrez]
AID - MMI4862 [pii]
AID - 10.1111/j.1365-2958.2005.04862.x [doi]
PST - ppublish
SO  - Mol Microbiol. 2005 Nov;58(3):774-90. doi: 10.1111/j.1365-2958.2005.04862.x.