Auto, a surface associated autolysin of Listeria monocytogenes required for entry into eukaryotic cells and virulence

• Published in: Molecular microbiology 2004-03, Vol.51 (6), p.1601-1614
• Main Authors: Cabanes, Didier, Dussurget, Olivier, Dehoux, Pierre, Cossart, Pascale
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Bacterial Adhesion; Bacterial Proteins; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Brain; Brain - microbiology; Cell Line; Eukaryotic Cells; Eukaryotic Cells - microbiology; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Humans; Intestines; Intestines - microbiology; Life Sciences; Listeria monocytogenes; Listeria monocytogenes - pathogenicity; Listeria monocytogenes - physiology; Listeriosis; Listeriosis - microbiology; Liver; Liver - microbiology; Lymph Nodes; Lymph Nodes - microbiology; Membrane Proteins; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Microbiology; Microbiology and Parasitology; Miscellaneous; N-Acetylmuramoyl-L-alanine Amidase; N-Acetylmuramoyl-L-alanine Amidase - chemistry; N-Acetylmuramoyl-L-alanine Amidase - genetics; N-Acetylmuramoyl-L-alanine Amidase - metabolism; Spleen; Spleen - microbiology; Virulence
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2003.03945.x

Summary Listeria monocytogenes is an opportunistic food‐borne human and animal pathogen. Several surface proteins expressed by this intracellular pathogen are critical for the infectious process. By in silico analysis we compared the surface protein repertories of L. monocytogenes and of the non‐pathogenic species Listeria innocua and identified a gene encoding a surface protein of L. monocytogenes absent in L. innocua. This gene that we named aut encodes a protein (Auto) of 572 amino acids containing a signal sequence, a N‐terminal autolysin domain and a C‐terminal cell wall‐anchoring domain made up of four GW modules. We show here that the aut gene is expressed independently of the virulence gene regulator PrfA and encodes a surface protein with an autolytic activity. We provide evidence that Auto is required for entry of L. monocytogenes into cultured non‐phagocytic eukaryotic cells. The low invasiveness of an aut deletion mutant correlates with its reduced virulence following intravenous inoculation of mice and oral infection of guinea pigs. During infection, the autolytic activity of Auto may also be critical. Auto appears thus as a novel type of L. monocytogenes virulence factor.