HOST SUSCEPTIBILITY FACTORS AND THEIR INFLUENCE ON BACTERIAL VIRULENCE IN MELIOIDOSIS

Abstract

B. pseudomallei is a causative agent of melioidosis, a disease endemic in South East Asia, Northern Australia. To understand the host factors that predispose individuals to developing severe melioidosis, mouse models were used. We used in vivo mouse infection as well as in vitro mouse splenocyte infection to characterize the possible host factors that could contribute to the pathogenesis of melioidosis. With these models, we first examined the role of IL-10, an anti-inflammatory cytokine in melioidosis. We found that splenocytes from the susceptible BALB/c mice produced more IL-10 as compared to splenocytes from the relatively more resistant C57BL/6 mice. Another mouse model we developed was used to examine the effect of glutathione in melioidosis. BALB/c mice deficient in glutathione were observed to die faster, had higher intracellular bacterial loads, and reduced production of the cytokines IL-12 and IFN-¿. We also discovered BipB, a T3SS3 effector protein from B. pseudomallei that could suppress cytokine production as well as host microbicidal activity. We believe that through our models, we can shed some light on the pathogenesis of B. pseudomallei.