A novel experimental immunomodulatory therapy against Nocardia brasiliensis in a BALB/c murine model.

Abstract

Mycetoma is recognized as a neglected tropical disease and there are still therapeutic challenges, especially in cases recalcitrant to standard therapy or with high risk of dissemination. Subcultures have been used previously to decrease the virulence of human pathogens. Previous reports have demonstrated that after carrying out 200 subcultures of Nocardia brasiliensis, a decrease in virulence was observed. To evaluate the effect of attenuated N.brasiliensis strains on the development of lesions in an established mycetoma infection. Female 8-12-week-old BALB/c mice were injected with N.brasiliensis suspension to establish a mycetoma. Sixty mice were selected and divided into three groups: two of these groups were inoculated in the dorsum with N.brasiliensis subcultured 200 and 400 times, respectively, while the third group served as control. The thickness of each lesion was measured with calipers every week for 12weeks. After 12weeks, we observed that inoculation of 1×105 colony-forming units of attenuated N.brasiliensis strains was able to modify the natural history of the infection, with a decrease in the size of the lesions, particularly with P400, compared with the control group (P<0.01). In this experimental evaluation of an immunomodulatory therapy with attenuated N.brasiliensis strains in a murine model, there was a greater stability in the size of the lesion over time in BALB/c mice inoculated with the P400 strain. This treatment could open the possibility of using the attenuated strain as immunomodulatory therapy in patients recalcitrant to standard therapy, with high risk of dissemination or who develop drug-related adverse effects.