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A Neisseria meningitidis NMB1966 mutant is impaired for invasion of respiratory epithelial cells, survival in human blood and for virulence in vivo

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Abstract

We sought to determine whether NMB1966, encoding a putative ABC transporter, has a role in pathogenesis. Compared to its isogenic wild-type parent strain Neisseria meningitidis MC58, the NMB1966 knockout mutant was less adhesive and invasive for human bronchial epithelial cells, had reduced survival in human blood and was attenuated in a systemic mouse model of infection. The transcriptome of the wild-type and the NMB1966 mutant was compared. The data are consistent with a previous functional assignment of NMB1966 being the ABC transporter component of a glutamate transporter operon. Forty-seven percent of all the differentially regulated genes encoded known outer membrane proteins or pathways generating complex surface structures such as adhesins, peptidoglycan and capsule. The data show that NMB1966 has a role in virulence and that remodelling of the outer membrane and surface/structures is associated with attenuation of the NMB1966 mutant.

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Acknowledgments

We thank Professor Philip Butcher, and Drs. Ken Laing, Jason Hinds, Kate Gould and Adam Witney (St George’s, University of London) for providing facilities and advice on real-time RT-PCR, supplying Pan-Neisseria microarray slides and submission of microarray data through ArrayExpress and Dr. KM Ho (Intensive Care Unit, Royal Perth Hospital) for assistance with statistical analysis.

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Authors and Affiliations

  1. Department of Paediatrics, Imperial College London, St Mary’s Campus, London, W2 1PG, UK

    Ming-Shi Li, Sunita Sinha, J. Simon Kroll & Paul R. Langford

  2. School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, 6000, Australia

    Noel Y. S. Chow & Steven A. R. Webb

  3. Centre for Emergency Preparedness and Response, Health Protection Agency, Porton Down, Salisbury, SP4 0JG, UK

    Denise Halliwell, Michelle Finney & Andrew R. Gorringe

  4. Microbiology and Infectious Diseases, Royal Perth Hospital, Perth, WA, 6000, Australia

    Mark W. Watson

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  1. Ming-Shi Li
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Correspondence to Paul R. Langford or Steven A. R. Webb.

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M.-S. Li and N.Y.S. Chow have contributed equally to the work.

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Li, MS., Chow, N.Y.S., Sinha, S. et al. A Neisseria meningitidis NMB1966 mutant is impaired for invasion of respiratory epithelial cells, survival in human blood and for virulence in vivo. Med Microbiol Immunol 198, 57–67 (2009). https://doi.org/10.1007/s00430-008-0105-2

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