Immunogenicity and biophysical properties of a<i>Nocardia brasiliensis</i>protease involved in pathogenesis of mycetoma

Licón-Trillo, Ángel; Castro-Corona, M Ángeles; Salinas-Carmona, Mario C.

doi:10.1016/s0928-8244(03)00102-0

Cited by 14 publications

(7 citation statements)

References 17 publications

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“…The bacterial strain was cultured and a crude cellular extract was prepared, and defatted with ethanol-ether to preserve proteolytic activities present in the extract as previously described [19,20]. We isolated the protease antigen in 3 steps briefly summarized as follows.…”

Section: Antigens and Immunizationmentioning

confidence: 99%

Immunosuppressive drugs have different effect on B lymphocyte subsets and IgM antibody production in immunized BALB/c mice

et al. 2009

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Infections are frequently associated with immunosuppressive therapy currently used to prevent organ rejection or treat autoimmune diseases. Such drugs suppress antibody production despite having different mechanisms of action. Antibodies are produced by a non-homogenous population of B lymphocyte subsets. B-1 cells produce natural antibodies and protect immediately after infection, while B2 cells produce antigen-specific IgM antibodies in a later response to infection. To understand how the immunosuppressive drugs affect antibody production by B cell populations, we immunized BALB/c mice with different antigens followed by administration of various immunosuppressive drugs. B-1a and B-1b lymphocytes from spleens of sacrificed animals were analyzed by flow cytometry, natural and antigen -specific IgG and IgM antibodies were determined by nephelometry and ELISA assays. Results showed that prednisone (PDN), cyclophosphamide (CYC), methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) decreased more than 60% of B-1a lymphocytes while cyclosporine (CsA) had little effect. Three drugs PDN, AZA and CYC suppressed the B-2 cells on day 30, while MTX affected this subpopulation early on day 5. Antigen-specific IgM antibodies were dramatically suppressed after 15 days of immunization in animals receiving PDN, CYC or AZA, while MMF, CsA and MTX showed little effect. Natural antibodies were equally decreased in all animals regardless of the specific drug used in treatment. These results will help to choose single or combinations of immunosuppressive drugs in the clinical setting.

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Section: Antigens and Immunizationmentioning

confidence: 99%

Immunosuppressive drugs have different effect on B lymphocyte subsets and IgM antibody production in immunized BALB/c mice

et al. 2009

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“…With this technique, a clinical correlation between anti-P24 antibody concentrations and active infection was found (14). P38 purified from an N. brasiliensis crude cell extract is a protease with strong caseinolytic activity; when injected into BALB/c mice, this antigen induced protection (6). Passive humoral immunity was also transferred with sera from animals immunized with heat-killed N. brasiliensis.…”

mentioning

confidence: 99%

Humoral Immunity through Immunoglobulin M Protects Mice from an Experimental Actinomycetoma Infection byNocardia brasiliensis

Salinas-Carmona

Pérez-Rivera

2004

Infect Immun

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An experimental model of infection with Nocardia brasiliensis, used as an example of a facultative intracellular pathogen, was tested. N. brasiliensis was injected into the rear foot pads of BALB/c mice to establish an infection. Within 30 days, infected animals developed a chronic actinomycetoma infection. Batch cultures of N. brasiliensis were used to purify P61, P38, and P24 antigens; P61 is a catalase, and P38 is a protease with strong caseinolytic activity. Active and passive immunizations of BALB/c mice with these three purified soluble antigens were studied. Protection was demonstrated for actively immunized mice. However, immunity lasted only 30 days. Other groups of immunized mice were bled at different times, and their sera were passively transferred to naive recipients that were then infected with N. brasiliensis. Sera collected 5, 6, and 7 days after donor immunization conferred complete, long-lasting protection. The protective effect of passive immunity decreased when sera were collected 2 weeks after donor immunization. However, neither the early sera (1-, 2-, and 3-day sera) nor the later sera (30-or 45-day sera) prevented the infection. Hyperimmune sera with the highest levels of immunoglobulin G (IgG) to N. brasiliensis antigens did not protect at all. The antigens tested induced two IgM peaks. The first peak was present 3 days after immunization but was not antigen specific and did not transfer protection. The second peak was evident 7 days after immunization, was an IgM response, was antigen specific, and conferred protection. This results clearly demonstrate that IgM antibodies protect the host against a facultative intracellular bacterium.

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“…There have been several experimentally described virulence factors of Nocardia, including catalase, superoxide dismutase, cell-wall lipids, and proteases, as well as some immunodominant antigens, using mainly N. cyriacigerogica GUH-2 (formerly N. asteroides ) and N. brasiliensis HUJEG-1 [21], [22], [23], [24], [25].…”

Section: Resultsmentioning

confidence: 99%

“…In N. brasiliensis , a catalase was described as the target of the humoral response in patients suffering mycetoma. At that time, the catalase was named P61 or katN [24]. katN is encoded by O3I_001640, and the closest ortholog proteins are found in N. cyriacigeorgica GUH-2 (87%) and in M. abscessus (85%).…”

Section: Resultsmentioning

confidence: 99%

Complete Genome Sequence Analysis of Nocardia brasiliensis HUJEG-1 Reveals a Saprobic Lifestyle and the Genes Needed for Human Pathogenesis

et al. 2013

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Nocardia brasiliensis is an important etiologic agent of mycetoma. These bacteria live as a saprobe in soil or organic material and enter the tissue via minor trauma. Mycetoma is characterized by tumefaction and the production of fistula and abscesses, with no spontaneous cure. By using mass sequencing, we determined the complete genomic nucleotide sequence of the bacteria. According to our data, the genome is a circular chromosome 9,436,348-bp long with 68% G+C content that encodes 8,414 proteins. We observed orthologs for virulence factors, a higher number of genes involved in lipid biosynthesis and catabolism, and gene clusters for the synthesis of bioactive compounds, such as antibiotics, terpenes, and polyketides. An in silico analysis of the sequence supports the conclusion that the bacteria acquired diverse genes by horizontal transfer from other soil bacteria, even from eukaryotic organisms. The genome composition reflects the evolution of bacteria via the acquisition of a large amount of DNA, which allows it to survive in new ecological niches, including humans.

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Immunogenicity and biophysical properties of aNocardia brasiliensisprotease involved in pathogenesis of mycetoma

Cited by 14 publications

References 17 publications

Immunosuppressive drugs have different effect on B lymphocyte subsets and IgM antibody production in immunized BALB/c mice

Immunosuppressive drugs have different effect on B lymphocyte subsets and IgM antibody production in immunized BALB/c mice

Humoral Immunity through Immunoglobulin M Protects Mice from an Experimental Actinomycetoma Infection byNocardia brasiliensis

Complete Genome Sequence Analysis of Nocardia brasiliensis HUJEG-1 Reveals a Saprobic Lifestyle and the Genes Needed for Human Pathogenesis

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