The research lab of Stanley M. Spinola, MD focuses on the bacterium Haemophilus ducreyi, which causes cutaneous ulcers in children in the tropics and the genital ulcer disease chancroid, which facilitates the transmission of HIV-1. The laboratory developed a model in which human volunteers are infected on the skin of the arm with the bacterium that is relevant to both syndromes. Features of the model include a low dose required for infection (1 to 100 CFU) and a clinical course and a cutaneous immune response that mimics naturally occurring disease.
In both experimental and natural infection, H. ducreyi resides in an abscess, and the primary mechanism by which the organism causes disease is evasion of phagocytosis. One major project in the laboratory is to determine the molecular interaction network between H. ducreyi and the host on a transcriptional level using RNA-sequencing; preliminary data indicate that H. ducreyi is primarily seeking nutrients such as ascorbic acid and adapting to anaerobiosis in vivo.
Another major project is to try to understand how H. ducreyi causes leg ulcers in children and by microbiome analysis discover other agents that cause this syndrome. The laboratory found that activation of a two-component system cripples the virulence of H. ducreyi and Neisseria gonorrhoeae in vivo. Investigators have identified small molecules that activate this system as potential antimicrobials.