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.