Duplication of genes encoding the immunodominant 38 kDa antigen in Mycobacterium intracellulare

Thangaraj, Harry

doi:10.1016/0378-1097(96)00370-9

Cited by 6 publications

(6 citation statements)

References 5 publications

(5 reference statements)

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“…It is not clear at the moment whether another such gene also exists in M. tuberculosis. A somewhat similar diversity also exists in M. intracellulare (46) (Fig. 5).…”

Section: Discussionsupporting

confidence: 64%

Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG

Lefèvre¹,

Braibant²,

Wit³

et al. 1997

J Bacteriol

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A gene encoding a protein homologous to the periplasmic ABC phosphate binding receptor PstS from Escherichia coli was cloned and sequenced from a gt11 library of Mycobacterium tuberculosis by screening with monoclonal antibody 2A1-2. Its degree of similarity to the E. coli PstS is comparable to those of the previously described M. tuberculosis phosphate binding protein pab (Ag78, Ag5, or 38-kDa protein) and another M. tuberculosis protein which we identified recently. We suggest that the three M. tuberculosis proteins share a similar function and could be named PstS-1, PstS-2, and PstS-3, respectively. Molecular modeling of their three-dimensional structures using the structure of the E. coli PstS as a template and their inducibility by phosphate starvation support this view. Recombinant PstS-2 and PstS-3 were produced and purified by affinity chromatography. With PstS-1, these proteins were used to demonstrate the specificity of three groups of monoclonal antibodies. Using these antibodies in flow cytometry and immunoblotting analyses, we demonstrate that the three genes are expressed and their protein products are present and accessible at the mycobacterial surface as well as in its culture filtrate. Together with the M. tuberculosis genes encoding homologs of the PstA, PstB, and PstC components we cloned before, the present data suggest that at least one, and possibly several, related and functional ABC phosphate transporters exist in mycobacteria. It is hypothesized that the mycobacterial gene duplications presented here may be a subtle adaptation of intracellular pathogens to phosphate starvation in their alternating growth environments.

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“…It is not clear at the moment whether another such gene also exists in M. tuberculosis. A somewhat similar diversity also exists in M. intracellulare (46) (Fig. 5).…”

Section: Discussionsupporting

confidence: 64%

Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG

Lefèvre¹,

Braibant²,

Wit³

et al. 1997

J Bacteriol

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“…A similar example has been recently reported, where it was suggested that a tandem gene duplication of the pstSl genes encoding phosphate binding proteins in Mycobactenum intracellulare was the result of evolutionary pressure for intracellular pathogenesis (Thangaraj et al 1996). However, in this case as well as every other instance of gene duplication cited in the examples above, the duplicated genes were not identical as was observed in this study with msa.…”

Section: Gene Duplication Of Msa In Renibacterium Salmoninarumcontrasting

confidence: 51%

Differential expression of the virulence-associated protein p57 and characterization of its duplicated gene msa in virulent and attenuated strains of Renibacterium salmoninarum

O'farrell¹,

Strom²

1999

Dis. Aquat. Org.

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Virulence mechanisms utilized by the salrnonld fish pathogen Renibactedum salmoninarum are poorly understood. One potential virulence factor is p57 (also designated MSA for major soluble antigen), an abundant 57 kDa soluble protein that is predominately localized on the bacterial cell surface with significant levels released into the extracellular milieu. Previous studies of an attenuated strain, MT 239, indicated that it differs from virulent strains in the amount of surface-associated p57. In this report, we show overall expression of p57 in R. salmoninarum MT 239 is considerably reduced as compared to a virulent strain, ATCC 33209. The amount of cell-associated p57 is decreased while the level of p57 in the culture supernatant is nearly equivalent between the strains. To determine if the lowered amount of cell-associated p57 was due to a sequence defect in p57, a genetic comparison was performed. Two copies of the gene encoding p57 (msal and msa2) were found in 33209 and MT 239, as well as in several other virulent isolates. Both copies from 33209 and MT 239 were cloned and sequenced and found to be identical to each other, and identical between the 2 strains. A comparison of msal and msa2 within each strain showed that their sequences diverge 40 base pairs 5' to the open reading frame, while sequences 3' to the open reading frame are essentially identical for at least 225 base pairs. Northern blot analysis showed no difference in steady state levels of msa mRNA between the 2 strains. These data suggest that while cell-surface localization of p57 may be important for R. salmoninarum virulence, the Wferences in localization and total p57 expression between 33209 and MT 239 are not due to differences in msa sequence or differences in steady state transcript levels.

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“…However, it is now evident that T-cell responses to this antigen are not specific, as T-cell proliferation was detected in 60% of both tuberculosis patients and healthy BCG-vaccinated subjects (71), and delayed-type hypersensitivity (DTH) responses to the 38-kDa antigen were elicited in guinea pigs sensitized with M. bovis, M. bovis BCG, M. kansasii, or M. intracellulare (27,69,71). The 38-kDa antigen gene is duplicated in M. intracellulare but absent from M. avium (54). A PCR assay designed to amplify the M. tuberculosis 38-kDa antigen gene gave positive results in M. bovis and M. africanum species, as well as M. tuberculosis, but not in other atypical mycobacteria (75).…”

Section: Discussionmentioning

confidence: 99%

Gamma Interferon Responses Induced by a Panel of Recombinant and Purified Mycobacterial Antigens in Healthy, Non-Mycobacterium bovisBCG-Vaccinated Malawian Young Adults

Black

Weir

Chaguluka

et al. 2003

Clin Vaccine Immunol

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We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-␥) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis There is great variation in the protection that Mycobacterium bovis BCG vaccines can provide against tuberculosis in different locations (17). In two large randomized controlled studies of BCG vaccination in Malawi and the United Kingdom, we have shown that prior to the vaccination of previously unvaccinated young adults in Malawi, over 60% of individuals show gamma interferon (IFN-␥) responses to purified protein derivative (PPD) from M. tuberculosis and that BCG vaccination provides only a moderate increase in this T-cell response (8). When PPDs from a number of nontuberculous environmental (atypical) mycobacteria were used to stimulate whole-blood cultures from the same subjects, PPDs from members of the M. avium-M. intracellulare-M. scrofulaceum complex induced stronger IFN-␥ responses than PPD from M. tuberculosis (6). To further define the mycobacterial species to which these subjects had been exposed, we have now used a panel of recombinant and purified antigens, with known species distributions, to test IFN-␥ responses, as a measure of the type 1 T-cell response induced by mycobacterial antigens, in day 6 supernatants from diluted whole-blood cultures. We have also assessed the potential of these recombinant antigens for identifying infection with M. tuberculosis and M. leprae, by studying the association between the IFN-␥ response to these antigens and the skin test response to M. tuberculosis PPD.Most studies of T-cell recognition of individual mycobacterial antigens have used patients infected with pathogenic mycobacteria or the contacts of these patients. Our study is unusual in that non-BCG-vaccinated, human immunodeficiency virus-negative, healthy individuals living in a rural area of northern Malawi have been tested for their ability to make a type 1 cytokine response to a panel of seven recombinant mycobacterial antigens and one purified native mycobacterial antigen. These subjects were clinically well at the time of testing and were recruited in their villages and homes.

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Duplication of genes encoding the immunodominant 38 kDa antigen in Mycobacterium intracellulare

Cited by 6 publications

References 5 publications

Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG

Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG

Differential expression of the virulence-associated protein p57 and characterization of its duplicated gene msa in virulent and attenuated strains of Renibacterium salmoninarum

Gamma Interferon Responses Induced by a Panel of Recombinant and Purified Mycobacterial Antigens in Healthy, Non-Mycobacterium bovisBCG-Vaccinated Malawian Young Adults

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