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 Chlamydophila 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-1 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-1 as a new molecule involved in chlamydial developmental cycle, although the intrinsic mechanisms deserve further studies.
Department of Biochemistry, Molecular Biology B and Immunology, University of Murcia, Murcia, Spain. jyelamos@um.es
José
J
Yélamos
Antonio J
AJ
Buendía
Nieves
N
Ortega
Yolanda
Y
Monreal
María C
MC
Gallego
Joaquin
J
Sánchez
Pablo
P
Ramírez
Pascual
P
Parrilla
María R
MR
Caro
Pedro
P
Aparicio
Jesús
J
Salinas
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016923:Cell Death; D023501:Chlamydophila / Q000187:drug effects* / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D016207:Cytokines; D018076:DNA, Complementary; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D007371:Interferon-gamma; D011065:Poly(ADP-ribose) Polymerases