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Infection and Immunity, April 2003, p. 2110-2119, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2110-2119.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Interactions between Brucella melitensis and Human Phagocytes: Bacterial Surface O-Polysaccharide Inhibits Phagocytosis, Bacterial Killing, and Subsequent Host Cell Apoptosis

Carmen M. Fernandez-Prada,1* Elzbieta B. Zelazowska,1 Mikeljon Nikolich,1 Ted L. Hadfield,2 R. Martin Roop II,3,4 Gregory L. Robertson,3 and David L. Hoover1

Department of Bacterial Diseases, Walter Reed Army Institute of Research,1 Department of Microbiology, Armed Forces Institute of Pathology, Washington, D.C.,2 Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana,3 Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina4

Received 1 July 2002/ Returned for modification 22 October 2002/ Accepted 18 December 2002

Brucellae are gram-negative intracellular pathogens that survive and multiply within host phagocytic cells. Smooth organisms present O-polysaccharides (OPS) on their surface. The wboA gene, which codes for the enzyme glycosyl transferase, is essential for the assembly of O-chain in Brucella. Deletion of wboA in smooth, virulent B. melitensis 16M results in a rough mutant designated WRR51. Unlike B. abortus, both smooth and rough strains of B. melitensis are resistant to complement-mediated killing. To determine the role of surface OPS in the interactions of B. melitensis with monocytes/macrophages (M/M), 16M and WRR51 were transformed with the plasmid pBBR1MCS-6y encoding green fluorescent protein, and the transformants were used to infect human mononuclear phagocytes with and without fresh human serum as a source of complement. Human monocytes were cultured in the presence of macrophage colony-stimulating factor to allow their differentiation into macrophages during the course of infection. Intracellular bacteria were easily visualized using fluorescence microscopy. Infection in M/M, identified by surface staining and fate of infected phagocytes, was quantitated by flow cytometry. Rough bacteria were internalized, with no requirement for opsonization by serum, at a higher rate than smooth organisms. Smooth B. melitensis survived and multiplied for at least 6 days inside M/M, but rough organisms were eliminated by death of the infected cells. In human monocytes cultured for 1 day without serum in order to trigger the apoptotic pathway, infection by rough brucellae accelerated phagocyte death; smooth brucellae inhibited apoptosis. This study suggests that the presence of surface OPS on live B. melitensis benefits the bacterium by preventing the death of macrophages, Brucella's preferred target for intracellular replication.

* Corresponding author. Mailing address: Department of Bacterial Diseases, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Bldg. 503, Rm. 2N57, Washington, DC 20307-5100. Phone: (301) 319-9658. Fax: (301) 319-9123. E-mail: Carmen.Fernandez-Prada{at}NA.AMEDD.ARMY.MIL.

Editor: A. D. O'Brien

Infection and Immunity, April 2003, p. 2110-2119, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2110-2119.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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