Maturation of lipoproteins by type II signal peptidase is required for phagosomal escape of Listeria monocytogenes.
Lipoproteins of Gram-positive bacteria are involved in a broad range of functions such as substrate binding and transport, antibiotic resistance, cell signaling, or protein export and folding. Lipoproteins are also known to initiate both innate and adaptative immune responses. However, their role in the pathogenicity of intracellular microorganisms is yet poorly understood. In Listeria monocytogenes, a Gram-positive facultative intracellular human pathogen, surface proteins have important roles in the interactions of the microorganism with the host cells. Among the putative surface proteins of L. monocytogenes, lipoproteins constitute the largest family. Here, we addressed the role of the signal peptidase (SPase II), responsible for the maturation of lipoproteins in listerial pathogenesis. We identified a gene, lsp, encoding a SPase II in the genome of L. monocytogenes and constructed a deltalsp chromosomal deletion mutant. The mutant strain fails to process several lipoproteins demonstrating that lsp encodes a genuine SPase II. This defect is accompanied by a reduced efficiency of phagosomal escape during infection of eucaryotic cells, and leads to an attenuated virulence. We show that lsp gene expression is strongly induced when bacteria are still entrapped inside phagosomes of infected macrophages. The data presented establish, thus, that maturation of lipoproteins is critical for efficient phagosomal escape of L. monocytogenes, a process temporally controlled by the regulation of Lsp production in infected cells.
Réglier-Poupet
Hélène
H
INSERM U570, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris cedex 15, France.
Frehel
Claude
C
Dubail
Iharilalao
I
Beretti
Jean-Luc
JL
Berche
Patrick
P
Charbit
Alain
A
Raynaud
Catherine
C
D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins; D001483:Base Sequence; D017931:DNA Primers; D016680:Genome, Bacterial; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000382:microbiology*; D014774:Virulence
D001426:Bacterial Proteins; D017931:DNA Primers; D008074:Lipoproteins; D016282:Aspartic Acid Endopeptidases; C095652:signal peptidase II