Inactivation of the srtA gene in Listeria monocytogenes inhibits anchoring of surface proteins and affects virulence.
During infection of their hosts, Gram-positive bacteria express surface proteins that serve multiple biological functions. Surface proteins harbouring a C-terminal sorting signal with an LPXTG motif are covalently linked to the cell wall peptidoglycan by a transamidase named sortase. Two genes encoding putative sortases, termed srtA and srtB, were identified in the genome of the intracellular pathogenic bacterium Listeria monocytogenes. Inactivation of srtA abolishes anchoring of the invasion protein InlA to the bacterial surface. It also prevents the proper sorting of several other peptidoglycan-associated LPXTG proteins. Three were identified by a mass spectrometry approach. The DeltasrtA mutant strain is defective in entering epithelial cells, similar to a DeltainlA mutant. In contrast to a DeltainlA mutant, the DeltasrtA mutant is impaired for colonization of the liver and spleen after oral inoculation in mice. Thus, L. monocytogenes srtA is required for the cell wall anchoring of InlA and, presumably, for the anchoring of other LPXTG-containing proteins that are involved in listerial infections.
Bierne
Hélène
H
Unité des Interactions Bactéries-Cellules, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris cedex 15, France.
Mazmanian
Sarkis K
SK
Trost
Matthias
M
Pucciarelli
M Graciela
MG
Liu
Gwen
G
Dehoux
Pierre
P
Jänsch
Lothar
L
Garcia-del Portillo
Francisco
F
Schneewind
Olaf
O
Cossart
Pascale
P
D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D005798:Genes, Bacterial; D008089:Listeria monocytogenes / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D008088:Listeriosis / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000382:microbiology; D013211:Staphylococcus aureus / Q000378:metabolism; D014774:Virulence
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases