Aggregation substance promotes adherence, phagocytosis, and intracellular survival of Enterococcus faecalis within human macrophages and suppresses respiratory burst.
The aggregation substance (AS) of Enterococcus faecalis, encoded on sex pheromone plasmids, is a surface-bound glycoprotein that mediates aggregation between bacteria thereby facilitating plasmid transfer. Sequencing of the pAD1-encoded Asa1 revealed that this surface protein contains two RGD motifs which are known to ligate integrins. Therefore, we investigated the influence of AS on the interaction of E. faecalis with human monocyte-derived macrophages which constitutively express beta(2) integrins (e.g., CD18). AS was found to cause a greater-than-fivefold increase in enterococcal adherence to macrophages and a greater-than-sevenfold increase in phagocytosis. Adherence was mediated by an interaction between the RGD motif and the integrin CD11b/CD18 (complement receptor type 3) as demonstrated by inhibition studies with monoclonal antibodies and RGD peptide. AS-bearing enterococci were significantly more resistant to macrophage killing during the first 3 h postinfection, probably due to inhibition of the respiratory burst as indicated by reduced concentrations of superoxide anion.
Süssmuth
S D
SD
Department of Medical Microbiology and Hygiene, University of Ulm, D-89081 Ulm, Germany.
Muscholl-Silberhorn
A
A
Wirth
R
R
Susa
M
M
Marre
R
R
Rozdzinski
E
E
D001422:Bacterial Adhesion; D001665:Binding Sites; D018821:CD18 Antigens / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003227:Conjugation, Genetic; D013293:Enterococcus faecalis / Q000502:physiology*; D006801:Humans; D008163:Luminescent Measurements; D016177:Macrophage-1 Antigen / Q000502:physiology; D008264:Macrophages / Q000382:microbiology*; D009842:Oligopeptides / Q000502:physiology; D010587:Phagocytosis; D016897:Respiratory Burst; D012724:Sex Attractants / Q000235:genetics
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D009842:Oligopeptides; D012724:Sex Attractants; C013065:cell aggregation factors; C047981:arginyl-glycyl-aspartic acid