Peptidylprolyl cis-trans isomerases of Legionella pneumophila: virulence, moonlighting and novel therapeutic targets.
Legionella pneumophila, typically a parasite of free-living protozoa, can also replicate in human alveolar macrophages and lung epithelial cells causing Legionnaires' disease in humans, a severe atypical pneumonia. The pathogen encodes six peptidylprolyl cis-trans isomerases (PPIases), which generally accelerate folding of prolyl peptide bonds, and influence protein folding. PPIases can be divided into three classes, cyclophilins, parvulins and FK506-binding proteins (FKBPs). They contribute to a multitude of cellular functions including bacterial virulence. In the present review, we provide an overview of L. pneumophila PPIases, discussing their known and anticipated functions as well as moonlighting phenomena. By taking the example of the macrophage infectivity potentiator (Mip) of L. pneumophila, we highlight the potential of PPIases as promising drug targets.
*Institut für Mikrobiologie, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
Janine
J
Rasch
Can M
CM
Ünal
Michael
M
Steinert
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001665:Binding Sites; D021983:Cyclophilins / Q000378:metabolism; D016952:Legionella pneumophila / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D014774:Virulence
D000900:Anti-Bacterial Agents; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase