A novel 27 kDa lipoprotein antigen from Mycobacterium bovis

Bigi, Fabiana; Espitia, Clara; Alito, A.; Zumárraga, Martín José; Romanó, Maria; Cravero, Silvio; Cataldi, Angel

doi:10.1099/00221287-143-11-3599

Cited by 44 publications

(44 citation statements)

References 36 publications

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“…LprG also has no described function in M. tuberculosis and no homology with other bacterial lipoproteins. LprG from M. bovis is recognized by serum from infected cattle suggesting that it is expressed during infection (39). Immunization with recombinant LprG was detrimental in a murine M. tuberculosis infection model consistent with the vaccine studies with LpqH (40).…”

Section: Discussionsupporting

confidence: 72%

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Gehring

Dobos

Belisle

et al. 2004

The Journal of Immunology

227

193

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MHC class II (MHC-II)-restricted CD4+ T cells are essential for control of Mycobacterium tuberculosis infection. This report describes the identification and purification of LprG (Rv1411c) as an inhibitor of primary human macrophage MHC-II Ag processing. LprG is a 24-kDa lipoprotein found in the M. tuberculosis cell wall. Prolonged exposure (>16 h) of human macrophages to LprG resulted in marked inhibition of MHC-II Ag processing. Inhibition of MHC-II Ag processing was dependent on TLR-2. Short-term exposure (<6 h) to LprG stimulated TLR-2-dependent TNF-α production. Thus, LprG can exploit TLR-2 signaling to inhibit MHC-II Ag processing in human macrophages. Inhibition of MHC-II Ag processing by mycobacterial lipoproteins may allow M. tuberculosis, within infected macrophages, to avoid recognition by CD4+ T cells.

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Section: Discussionsupporting

confidence: 72%

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Gehring

Dobos

Belisle

et al. 2004

The Journal of Immunology

227

193

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“…The fact that the 30-kDa band was not radiolabeled indicates that the labeling is not due to nonspecific lipid absorption. Furthermore, it has been shown that the 27-kDa antigen has a signal peptidase type II site (7). For E. coli, the signal peptidase II enzyme required diacylglyceryl modification prior to cleavage (20,26); this means that diacylglyceryl mod- FIG.…”

Section: Discussionmentioning

confidence: 99%

TheMycobacterium tuberculosisRecombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

et al. 2003

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Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

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“…Much less information exists about the protein product encoded by lprG. Immediately upstream of Rv1410c is lprG, which codes for LprG, a lipoprotein with no conserved enzymatic or functional domains save for the lipid attachment site that defines lipoproteins (1). LprG is a secreted, surface-expressed lipoprotein and has been shown to modulate host immune function (7).…”

mentioning

confidence: 99%

Function of a Mycobacterial Major Facilitator Superfamily Pump Requires a Membrane-Associated Lipoprotein

Farrow

Rubín

2008

J Bacteriol

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The lprG-Rv1410c operon is critical for the survival of Mycobacterium tuberculosis during infection, but very little is known about the functions of its proteins. LprG is a lipoprotein, and Rv1410c encodes the major facilitator superfamily small molecule transporter P55. P55 likely exports small molecules outside of the bacterial cell, but the function of LprG is unclear. A deletion of the homologous operon in Mycobacterium smegmatis is more susceptible to ethidium bromide, and drug resistance is restored by the intact operon from M. tuberculosis. The multidrug resistance pump inhibitor reserpine inhibits resistance to ethidium bromide in both wild-type M. smegmatis and the complemented mutant, suggesting that P55-mediated transport is responsible for drug resistance and that ethidium bromide is a novel substrate for P55. In addition to hypersensitivity to ethidium bromide, cells that lack the lprG-Rv1410c operon display abnormal colony morphology and are defective for sliding motility, properties that suggest an alteration of cell wall composition. Strikingly, both ethidium bromide transport and normal cell surface properties require functional P55 and LprG, as neither alone is sufficient to restore function to the deletion mutant. Thus, P55 requires the cell surface lipoprotein for normal function.The two genes of the lprG-Rv1410c operon are crucial for the survival of Mycobacterium tuberculosis during infection. Transposon insertions in either gene are severely attenuating in mice, with no obvious defects during normal vegetative growth (13). A knockout of the operon is also profoundly attenuated in vivo (3).Although lprG and Rv1410c are clearly required by the bacterium during infection, almost nothing is known about the biologic functions of the products of the operon. P55, the protein encoded by Rv1410c, is a small molecule transporter of the major facilitator superfamily (MFS) (14). The transporter belongs to the drug/Hϩ antiporter 14 transmembrane domain (DHA14) family, whose members are thought to export cationic small molecules by proton motive force (11). Characterized members of the DHA14 transporter family were identified based on their ability to confer drug resistance when heterologously expressed, and P55 from M. tuberculosis has been reported to confer resistance to tetracycline and aminoglycosides when expressed in Mycobacterium smegmatis (14). However, very few physiologic substrates are known for the DHA14 pumps, and none have been identified for P55. Much less information exists about the protein product encoded by lprG. Immediately upstream of Rv1410c is lprG, which codes for LprG, a lipoprotein with no conserved enzymatic or functional domains save for the lipid attachment site that defines lipoproteins (1). LprG is a secreted, surface-expressed lipoprotein and has been shown to modulate host immune function (7).Whatever the individual proteins do, it is likely that their biologic roles relate to a common pathway. The genomic organization of lprG and Rv1410c in an operon (2) suggests that ...

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A novel 27 kDa lipoprotein antigen from Mycobacterium bovis

Cited by 44 publications

References 36 publications

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

TheMycobacterium tuberculosisRecombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

Function of a Mycobacterial Major Facilitator Superfamily Pump Requires a Membrane-Associated Lipoprotein

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