Meningococcal outer membrane protein NhhA is essential for colonization and disease by preventing phagocytosis and complement attack.
Neisseria meningitidis is a leading cause of meningitis and septicemia worldwide, with a rapid onset of disease and a high morbidity and mortality. NhhA is a meningococcal outer membrane protein included in the family of trimeric autotransporter adhesins. The protein binds to the extracellular matrix proteins heparan sulfate and laminin and facilitates attachment to host epithelial cells. In this study, we show that NhhA is essential for bacterial colonization of the nasopharyngeal mucosa in a murine model of meningococcal disease. Successful colonization depends on bacterial attachment but also to the capacity to overcome innate host immune responses. We found that NhhA protected bacteria from phagocytosis, which is important for the mucosal survival of bacteria. In addition, NhhA mediated extensive serum resistance that increased bacterial survival in blood and promoted lethal sepsis. The presence of NhhA protected bacteria from complement-mediated killing by preventing the deposition of the membrane attack complex. Taken together, the results of this work reveal that NhhA inhibits phagocytosis and protects bacteria against complement-mediated killing, which enhances both nasal colonization and the development of sepsis in vivo.
Sjölinder
Hong
H
Department of Medical Biochemistry and Microbiology, Biomedical Centrum, Uppsala University, P.O. Box 582, Uppsala, Sweden.
Eriksson
Jens
J
Maudsdotter
Lisa
L
Aro
Helena
H
Jonsson
Ann-Beth
AB
D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D002460:Cell Line; D003165:Complement System Proteins / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D008589:Meningococcal Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009297:Nasal Mucosa / Q000382:microbiology; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D010587:Phagocytosis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018829:Adhesins, Bacterial; D003165:Complement System Proteins
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