Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death members of the Bcl2 protein family.
To establish a vacuole that supports bacterial replication, Legionella pneumophila translocates a large number of bacterial proteins into host cells via the Dot/Icm type IV secretion system. Functions of most of these translocated proteins are unknown, but recent investigations suggest their roles in modulating diverse host processes such as vesicle trafficking, autophagy, ubiquitination, and apoptosis. Cells infected by L. pneumophila exhibited resistance to apoptotic stimuli, but the bacterial protein directly involved in this process remained elusive. We show here that SidF, one substrate of the Dot/Icm transporter, is involved in the inhibition of infected cells from undergoing apoptosis to allow maximal bacterial multiplication. Permissive macrophages harboring a replicating sidF mutant are more apoptotic and more sensitive to staurosporine-induced cell death. Furthermore, cells expressing SidF are resistant to apoptosis stimuli. SidF contributes to apoptosis resistance in L. pneumophila-infected cells by specifically interacting with and neutralizing the effects of BNIP3 and Bcl-rambo, two proapoptotic members of Bcl2 protein family. Thus, inhibiting the functions of host pro-death proteins by translocated effectors constitutes a mechanism for L. pneumophila to protect host cells from apoptosis.
Banga
Simran
S
Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907, USA.
Gao
Ping
P
Shen
Xihui
X
Fiscus
Valena
V
Zong
Wei-Xing
WX
Chen
Lingling
L
Luo
Zhao-Qing
ZQ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D016952:Legionella pneumophila / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D020298:U937 Cells
C431152:BCL2L13 protein, human; C090121:BNIP3 protein, human; D001426:Bacterial Proteins; D008565:Membrane Proteins; D050505:Mutant Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019311:Staurosporine