IgM but not IgG monoclonal anti-Nocardia brasiliensisantibodies confer protection against experimental actinomycetoma in BALB/c mice

Abstract

Nocardia brasiliensis is a facultative intracellular microorganism that produces a human chronic infection known as actinomycetoma. Human and mouse anti-N. brasiliensis antibody response identify P24, P26 and P61 immunodominant antigens. In this work, we generated immunoglobulin M (IgM) and IgG monoclonal antibodies (mAbs) specific to immunodominant P61 antigen. The monoclonal IgM (NbM1) and IgG2a (NbG1) antibodies were assessed for their in vitro bactericidal activity, in vivo protective effect and ability to block catalase activity. These mAbs specifically recognized P61, but they did not inhibit its enzyme activity. The in vitro bactericidal effect of NbG1 was higher than the killing ability of the IgM mAb. In vivo experiments with a murine model of experimental infection with N. brasiliensis injected into rear footpads was used to test the effect of NbM1 and NbG1. The negative untreated group developed a chronic actinomycetoma within 4 weeks. IgM mAbs conferred protection to BALB/c mice infected with N. brasiliensis. IgG mAb lacked this protective effect. IgM mAb showed a dose-response correlation between antibody concentration and lesion size. These results demonstrate that humoral immune response mediated by antigen-specific IgM antibody protects against an intracellular bacterial infection.

Complete Genome Sequence of Nocardia brasiliensis HUJEG-1

“…To date, from the more than 30 Nocardia species reported (2, 10), only one genome sequence has been published: N. farcinica IFM 10152 (5). In the present report, we describe the genome sequence of N. brasiliensis HUJEG-1 (ATCC 700358), a strain that has largely been used for in vitro and in vivo experiments (1,4,9,12).…”

In Vitro Activity of ACH-702, a New Isothiazoloquinolone, against Nocardia brasiliensis Compared with Econazole and the Carbapenems Imipenem and Meropenem Alone or in Combination with Clavulanic Acid

“…We studied 30 isolates from the collection of the Laboratorio Interdisciplinario de Investigación Dermatológica of the Servicio de Dermatología, Hospital Universitario, Universitario de Nuevo León, including N. brasiliensis HUJEG-1, which was utilized previously in other in vitro and in vivo assays (11,17). All of the isolates tested came from human cases of actinomycetoma and were identified as N. brasiliensis by biochem-ical methods and by nucleotide sequence analysis of a fragment of the 16S RNA gene of the small ribosomal unit as previously described (17).…”

Decrease of virulence for BALB/c mice produced by continuous subculturing of Nocardia brasiliensis

“…The production of an immune cellular response seems to be essential in order to stop infection [4]. However, it has also been claimed that the humoral immune response, particularly IgM subtype antibodies, plays an important role in resistance to infection [5]. …”