Available carbon source influences the resistance of Neisseria meningitidis against complement.
Neisseria meningitidis is an important cause of septicaemia and meningitis. To cause disease, the bacterium must acquire essential nutrients for replication in the systemic circulation, while avoiding exclusion by host innate immunity. Here we show that the utilization of carbon sources by N. meningitidis determines its ability to withstand complement-mediated lysis, through the intimate relationship between metabolism and virulence in the bacterium. The gene encoding the lactate permease, lctP, was identified and disrupted. The lctP mutant had a reduced growth rate in cerebrospinal fluid compared with the wild type, and was attenuated during bloodstream infection through loss of resistance against complement-mediated killing. The link between lactate and complement was demonstrated by the restoration of virulence of the lctP mutant in complement (C3(-/-))-deficient animals. The underlying mechanism for attenuation is mediated through the sialic acid biosynthesis pathway, which is directly connected to central carbon metabolism. The findings highlight the intimate relationship between bacterial physiology and resistance to innate immune killing in the meningococcus.
Exley
Rachel M
RM
The Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
Shaw
Jonathan
J
Mowe
Eva
E
Sun
Yao-Hui
YH
West
Nicholas P
NP
Williamson
Michael
M
Botto
Marina
M
Smith
Harry
H
Tang
Christoph M
CM
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007113:Immunity, Innate; D019344:Lactic Acid / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology*; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis; D009345:Neisseria meningitidis / Q000276:immunology / Q000472:pathogenicity*; D051381:Rats; D017208:Rats, Wistar
D001426:Bacterial Proteins; D003176:Complement C3; C501877:IctP protein, Neisseria meningitidis; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D019344:Lactic Acid; D019158:N-Acetylneuraminic Acid