The Journal of Experimental Medicine
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Published 16 May 2005. doi:10.1084/jem.20041548
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 10, 1637-1645
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ARTICLE

 Available carbon source influences the resistance of Neisseria meningitidis against complement

Rachel M. Exley1, Jonathan Shaw2, Eva Mowe1, Yao-hui Sun1, Nicholas P. West1, Michael Williamson3, Marina Botto4, Harry Smith5, and Christoph M. Tang1

1 The Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK
2 Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, S10 2RX, UK
3 Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK
4 Faculty of Medicine, Rheumatology Section, Imperial College London, W12 ONN, UK
5 The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

CORRESPONDENCE Christoph M. Tang c.tang{at}imperial.ac.uk

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.

Abbreviations used: C.I., competitive index; CSF, cerebrospinal fluid; PEP, phosphoenol pyruvate.

R. Exley and J. Shaw contributed equally to this work.


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