This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Leid, J. G.
Right arrow Articles by Cope, E. K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leid, J. G.
Right arrow Articles by Cope, E. K.

 Previous Article  |  Next Article 

Infection and Immunity, October 2009, p. 4559-4566, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00075-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Flagellum-Mediated Biofilm Defense Mechanisms of Pseudomonas aeruginosa against Host-Derived Lactoferrin {triangledown}

Jeff G. Leid,1* Mathias Kerr,1 Candice Selgado,1 Chelsa Johnson,1 Gabriel Moreno,1 Alyssa Smith,1 Mark E. Shirtliff,2 George A. O'Toole,3 and Emily K. Cope1

Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona 86001,1 Department of Biomedical Sciences, University of Maryland, Baltimore, Maryland 21201,2 Department of Microbiology, Dartmouth University School of Medicine, Hanover, New Hampshire 037553

Received 20 January 2009/ Returned for modification 8 April 2009/ Accepted 25 July 2009

Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant lacks flagella, which results in defects in early biofilm development (up to 36 h). For these experiments, the flgK-disrupted strain and the parental strain (PA14) were used in a modified version of the 96-well plate microtiter assay. Biofilms were challenged with freshly isolated human leukocytes for 4 to 6 h and viable bacteria enumerated by CFU. Subsequent to the challenge, both mononuclear cells (monocytes and lymphocytes) and neutrophils, along with tumor necrosis factor alpha (TNF-{alpha}), were required for optimal killing of the flgK biofilm bacteria. We identified a cytokine cross talk network between mononuclear cells and neutrophils that was essential to the production of lactoferrin and bacterial killing. Our data suggest that TNF-{alpha} is secreted from mononuclear cells, causing neutrophil activation, resulting in the secretion of bactericidal concentrations of lactoferrin. These results extend previous studies of the importance of lactoferrin in the innate immune defense against bacterial biofilms.

* Corresponding author. Mailing address: Center for Microbial Genetics and Genomics, Laboratory of Biofilm Pathogenesis and Immunology, Northern Arizona University, 21 S. Beaver Street, Bldg. 88, Flagstaff, AZ 86011. Phone: (928) 523-8034. Fax: (928) 523-7500. E-mail: Jeff.Leid{at}nau.edu

{triangledown} Published ahead of print on 3 August 2009.

Editor: A. Camilli

Infection and Immunity, October 2009, p. 4559-4566, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00075-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»