Imaging of disease dynamics during meningococcal sepsis.
Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients.
Sjölinder
Hong
H
Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
Jonsson
Ann-Beth
AB
D018829:Adhesins, Bacterial / Q000502:physiology; D000818:Animals; D016470:Bacteremia / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology; D018988:Bacterial Translocation; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000382:microbiology; D018450:Disease Progression; D005260:Female; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000502:physiology; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid / Q000382:microbiology; D008589:Meningococcal Infections / Q000097:blood / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009296:Nasal Cavity / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012137:Respiratory System / Q000382:microbiology; D018805:Sepsis / Q000382:microbiology / Q000473:pathology*; D013961:Thyroid Gland / Q000382:microbiology
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C497857:CD46 protein, human; D008164:Luminescent Proteins; D051916:Membrane Cofactor Protein; D011993:Recombinant Fusion Proteins; C090348:Opa protein, Neisseria