Biochemical and Biophysical Research Communications, Vol.324, No.2, 840-848, 2004
Genetic and pharmacological inhibition of poly(ADP-ribose) polymerase-1 interferes in the chlamydial life cycle
Chlamydiaceae are intracellular bacteria responsible for a variety of infections, ranging from asymptomatic to very severe, in humans and animals. We have investigated the role of poly(ADP-ribose) polymerase-1 (PARP-1) in Chlainydophila abortus infection using PARP-1(-/-) and their littermates PARP-1(+/+) mice. Infection was resolved more efficiently by PARP-1(-/-) than PARP-1(+/+) mice. However, the inflammatory response was similar in both strains, suggesting a potential role for PARP-1 in the cross-talk between this microorganism and the host cells. PARP-1(-/-) fibroblasts showed a 10-fold lower rate of chlamydiae production than PARP-1(+/+). Moreover, a strong inhibition of bacterial production was also observed after pharmacological inhibition of PARP-1 activity in McCoy cells. Likewise, PARP-I inhibition induced a higher level of cell death of infected cells, interfering in this way with the normal bacterial cell cycle. Overall, we identify PARP-I as a new molecule involved in chlamydial developmental cycle, although the intrinsic mechanisms deserve further studies. (C) 2004 Elsevier Inc. All rights reserved.
Keywords:PARP-1;intracellular bacteria;chlamydiae;infection;inflammation;developmental cycle;cell death