Streptococcus pyogenes expressing M and M-like surface proteins are phagocytosed but survive inside human neutrophils.
Strains of the Gram-positive human pathogen Streptococcus pyogenes (group A streptococcus) that express surface-associated M or M-like proteins survive and grow in non-immune fresh human blood. This is generally accepted to be caused by an antiphagocytic property of these proteins. However, in most previous studies, an inhibition of the internalization of the bacteria into host cells has not been studied or not directly demonstrated. Therefore, in the present paper, we used flow cytometry, fluorescence microscopy and electron microscopy to study phagocytosis by human neutrophils of wild-type S. pyogenes and strains deficient in expression of M protein and/or the M-like protein H. The results demonstrate that all strains of S. pyogenes tested, including the wild-type AP1 strain, induce actin polymerization and are efficiently phagocytosed by human neutrophils. In addition, using classical bactericidal assays, we show that the wild-type AP1 strain can survive inside neutrophils, whereas mutant strains are rapidly killed. We conclude that the ability of virulent S. pyogenes to survive and multiply in whole blood is most likely not possible to explain only by an antiphagocytic effect of bacterial surface components. Instead, our data suggest that bacterial evasion of host defences occurs intracellularly and that survival inside human neutrophils may contribute to the pathogenesis of S. pyogenes and the recurrence of S. pyogenes infections.
Staali
Leïla
L
Department of Cell and Molecular Biology, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden.
Mörgelin
Matthias
M
Björck
Lars
L
Tapper
Hans
H
D000199:Actins / Q000378:metabolism; D000942:Antigens, Bacterial / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology* / Q000648:ultrastructure; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D013297:Streptococcus pyogenes / Q000378:metabolism* / Q000648:ultrastructure
D000199:Actins; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D009895:Opsonin Proteins; C014689:streptococcal M protein