INTERACTION OF INSULIN WITH PSEUDOMONAS-PSEUDOMALLEI

Pseudomonas pseudomallei is the causative agent of melioidosis, a dise ase being increasingly recognized as an important cause of morbidity a nd mortality in many regions of the world. An intriguing observation r egarding melioidosis is that a significant percentage of patients who develop the disease have preexisting diabetes mellitus. In this regard , we have tested the hypothesis that insulin may modulate the growth o f P. pseudomallei. We have demonstrated that insulin markedly inhibits the growth of P. pseudomallei in vitro and in vivo. The growth rate o f P. pseudomallei in minimal medium containing human recombinant insul in was significantly lower than that of control cultures containing no insulin. P. pseudomallei grew at an increased rate in serum samples o btained from diabetic rats compared with that in serum samples obtaine d from control animals. When the insulin level was restored by the add ition of human recombinant insulin, the growth rate was reduced to a l evel similar to that seen in control serum. P. pseudomallei also grew significantly better in insulin-depleted human serum than control huma n serum. I-125-insulin binding studies demonstrated that P. pseudomall ei possesses a specific, high-affinity binding site for human insulin. In in vivo studies, rats made diabetic by streptozotocin injection (8 0 mg/kg of body weight, intraperitoneally) were significantly more sus ceptible to P. pseudomallei septicemia than control rats. Thus, it app ears that serum insulin levels may play a significant role in modulati ng the pathogenesis of P. pseudomallei septicemic infections.