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Infection and Immunity, January 2009, p. 45-51, Vol. 77, No. 1
0019-9567/09/$08.00+0 doi:10.1128/IAI.00968-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Richard Sim,2,
Linda Goodwin,3
Megan Winterbotham,1
Muriel C. Schneider,1
Robert C. Read,3 and
Christoph M. Tang1*
Centre for Molecular Microbiology and Infection, Department of Microbiology, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom,1 Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, United Kingdom,2 Division of Genomic Medicine, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom3
Received 1 August 2008/ Returned for modification 24 September 2008/ Accepted 9 October 2008
Neisseria meningitidis is an exclusively human pathogen that has evolved primarily to colonize the nasopharynx rather than to cause systemic disease. Colonization is the most frequent outcome following meningococcal infection and a prerequisite for invasive disease. The mechanism of colonization involves attachment of the organism to epithelial cells via bacterial type IV pili (Tfp), but subsequent events during colonization remain largely unknown. We analyzed 576 N. meningitidis mutants for their capacity to colonize human nasopharyngeal tissue in an organ culture model to identify bacterial genes required for colonization. Eight colonization-defective mutants were isolated. Two mutants were unable to express Tfp and were defective for adhesion to epithelial cells, which is likely to be the basis of their attenuation in nasopharyngeal tissue. Three other mutants are predicted to have lost previously uncharacterized surface molecules, while the remaining mutants have transposon insertions in genes of unknown function. We have identified novel meningococcal colonization factors, and this should provide insights into the survival of this important pathogen in its natural habitat.
Published ahead of print on 20 October 2008.
R.M.E. and R.S. contributed equally to this study.
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