The Mycobacterium avium complex (MAC) is the most significant of the environmental mycobacteria that cause disease in susceptible humans. Most MAC infections are thought to come from stably colonized drinking water supplies. The predominant way of life for bacteria in water is growth in surface-adherent biofilms, and recent studies have shown that MAC is no exception. It is present in vast numbers in biofilm samples taken from water distribution systems, and it appears to be the dominant Mycobacterium species in such environments. Genetic approaches have been used to analyze biofilm formation by the fast-growing model species M. smegmatis; however the genetics of biofilm formation by MAC remains to be explored. Using newly developed genetic and genomic tools, combined with authentic laboratory models of MAC biofilm development, we will conduct the first such investigation.
The specific aims of this exploratory project are 1) to identify MAC genes involved in the early stages of biofilm formation by using a novel """"""""transposome"""""""" mutagenesis approach, and 2) to identify MAC genes involved in the formation of mature two-species biofilms by using signature-tagged mutagenesis and transposon site hybridization. By establishing methods and conditions for genetic analysis of biofilm formation by MAC, we will begin to shed light on an aspect of mycobacterial biology that is almost entirely uncharacterized. The results will improve our understanding of the microbial ecology of environmental mycobacteria, and they may lead to improved methods for protecting susceptible people from MAC infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI061006-02
Application #
6908151
Study Section
Special Emphasis Panel (ZRG1-IDM-N (90))
Program Officer
Sizemore, Christine F
Project Start
2004-07-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
2
Fiscal Year
2005
Total Cost
$205,741
Indirect Cost
Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
070967955
City
Seattle
State
WA
Country
United States
Zip Code
98109
Cangelosi, Gerard A; Do, Julie S; Freeman, Robert et al. (2006) The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. Antimicrob Agents Chemother 50:461-8
Freeman, Robert; Geier, Henriette; Weigel, Kris M et al. (2006) Roles for cell wall glycopeptidolipid in surface adherence and planktonic dispersal of Mycobacterium avium. Appl Environ Microbiol 72:7554-8
Horan, Kathleen L; Freeman, Robert; Weigel, Kris et al. (2006) Isolation of the genome sequence strain Mycobacterium avium 104 from multiple patients over a 17-year period. J Clin Microbiol 44:783-9