The type II signal peptidase of Legionella pneumophila.
Legionella pneumophila is a facultative intracellular Gram-negative bacterium that has become an important cause of community-acquired and nosocomial pneumonia. Recent studies concerning the unravelling of bacterial virulence have suggested the involvement of protein secretion systems in bacterial pathogenicity. In this respect, the type II signal peptidase (LspA), which is specifically required for the maturation of lipoproteins, is of particular interest. This paper reports the cloning and functional characterization of the L. pneumophila lspA gene encoding the type II signal peptidase (SPase II). Activity of the L. pneumophila LspA was demonstrated using a globomycin sensitivity assay in Escherichia coli. In L. pneumophila, the lspA gene is flanked by the isoleucyl-tRNA synthetase (ileS) gene and the gene encoding a 2-hydroxy-3-deoxy-phosphogluconate aldolase. Although there is no apparent physiological connection, transcriptional analysis demonstrated that, as in some other Gram-negative bacteria, lspA is cotranscribed with ileS in L. pneumophila. Finally, in silico analysis revealed that several proteins known to be crucial for virulence and intracellular growth of L. pneumophila are predicted to be lipoproteins. These include, in particular, proteins involved in protein secretion and motility. Results obtained strongly suggest an important role for LspA in the pathogenicity of L. pneumophila, making it a promising new target for therapeutic intervention.
Geukens
Nick
N
Laboratory of Bacteriology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
De Buck
Emmy
E
Meyen
Eef
E
Maes
Liesbeth
L
Vranckx
Leen
L
Van Mellaert
Lieve
L
Anné
Jozef
J
Lammertyn
Elke
E
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D016952:Legionella pneumophila / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D010455:Peptides; C017339:globomycin; D016282:Aspartic Acid Endopeptidases; C095652:signal peptidase II