Mechanisms of pathogenesis in Listeria monocytogenes infection. V. Early imbalance in host energy metabolism during experimental listeriosis.

Early changes in hepatic carbohydrate metabolism without apparent hepatocyte dysfunction were reported previously in mice infected with Listeria monocytogenes. This study was undertaken to examine possible imbalance in host regulatory mechanisms which might be responsible for these changes. Female CD-1 mice fasted 12 hr prior to the experiments were injected intraperitoneally with 10(5), 10(6), or 10(7)Listeria. Control mice received either 10(9) heat-killed Listeria or 150 mug of Salmonella typhimurium lipopolysaccharide. Hepatic glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and nicotinamide adenine dinucleotide (NAD) (NAD(+), NADH, NADP(+), and NADPH) levels were assayed periodically. Activities of ATP hydrolyzing enzyme and NAD glycohydrolase were measured at various intervals after infection. Decreases in glycogen occurred as early as 10 hr after infection. Responses in the controls differed from those in infected mice. Hepatic ATP levels decreased as early as 10 hr after infection, with concomitant increases noted in ADP. Hepatic ATP hydrolyzing enzyme activity increased as the infection progressed. Decreases were noted in hepatic NAD levels, with the greatest reduction in the reduced form of NAD. Slight changes were observed after 10 hr, and greater differences were noted 20 hr after infection. The magnitude of these biochemical changes appeared to be dose-dependent. Significant increases in hepatic NAD glycohydrolase activity were noted as the infection progressed. Small but significant increases in serum inorganic phosphate were noted 10 and 20 hr after infection, with a larger increase observed 30 hr after infection. The results indicate impairment of host energy metabolism early in the course of experimental listeriosis.