Polymicrobial communities are found on oral cavity surfaces as biofilms, embedded in a matrix of host salivary components and microbial extracellular products. These communities provide an infection source for diseases of the oral hard and soft tissues, and for systemic conditions. Communication reactions between the micro-organisms modulate the structure, composition and pathogenic potential of the communities. The oral streptococci are especially important in this respect because they are primary colonizers of oral cavity surfaces. Their deposition provides an attachment substrate for colonization by potentially pathogenic organisms such as Porphyromonas gingivalis and the fungus Candida albicans, which is the cause of most yeast infections in humans. Co-adhesion between C. albicans and oral bacteria is proposed to facilitate oral carriage and persistence of C. albicans, leading to disease conditions such as denture-induced stomatitis, oral candidiasis, periodontitis, and root canal infections. Studies have demonstrated that inter-microbial binding of Streptococcus gordonii and C. albicans involves complementary and co-operative adhesin-receptor molecules. Streptococcal cell surface-associated SspB adhesin, a member of the Antigen I/II protein family, binds C. albicans hyphal cell surface glycoprotein Als3p, resulting in close engagement of the surface molecules on the partner cell types. These adhesion processes drive the development and accumulation of mixed species biofilms that are morphologically, physiologically and pathogenically unique.
The aims of this proposal are to: define the molecular mechanisms of C. albicans surface protein interactions with S. gordonii;characterize the signaling processes occurring in polymicrobial community development;determine the mechanisms of communication between C. albicans and P. gingivalis;investigate the impact of co-colonization in vivo.
These aims, while covering a range of factors, will permit detailed analyses of molecular communication systems occurring between co-colonizing bacteria and fungi. Characterization of the mechanisms involved in co-colonization of denture materials, oral mucosa, and of sub-gingival tissues, will provide greater understanding of the factors relevant to polymicrobial-mediated oral disease initiation and progression at these sites. Potential targets for inhibition of co-adhesion and community development can thus be identified, and these may ultimately prove a means for the control of infection by C. albicans.

Public Health Relevance

Fungi have emerged as major causes of human disease. Candida yeast infections are a serious threat to public health. This research devises new methods for controlling or preventing growth of Candida albicans in the mouth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
4R01DE016690-07
Application #
8440701
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lunsford, Dwayne
Project Start
2006-07-17
Project End
2016-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
7
Fiscal Year
2013
Total Cost
$371,500
Indirect Cost
$19,085
Name
University of Bristol
Department
Type
DUNS #
225051309
City
Bristol
State
Country
United Kingdom
Zip Code
BS8 1-TH
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Dutton, Lindsay C; Nobbs, Angela H; Jepson, Katy et al. (2014) O-mannosylation in Candida albicans enables development of interkingdom biofilm communities. MBio 5:e00911
Hajishengallis, George; Lamont, Richard J (2014) Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol 44:328-38
Moses, Peter J; Power, Daniel A; Jesionowski, Amy M et al. (2013) Streptococcus gordonii collagen-binding domain protein CbdA may enhance bacterial survival in instrumented root canals ex vivo. J Endod 39:39-43
Nobbs, A H; Jenkinson, H F; Jakubovics, N S (2011) Stick to your gums: mechanisms of oral microbial adherence. J Dent Res 90:1271-8
Jenkinson, Howard F (2011) Beyond the oral microbiome. Environ Microbiol 13:3077-87
Silverman, Richard J; Nobbs, Angela H; Vickerman, M Margaret et al. (2010) Interaction of Candida albicans cell wall Als3 protein with Streptococcus gordonii SspB adhesin promotes development of mixed-species communities. Infect Immun 78:4644-52
Brady, L Jeannine; Maddocks, Sarah E; Larson, Matthew R et al. (2010) The changing faces of Streptococcus antigen I/II polypeptide family adhesins. Mol Microbiol 77:276-86
Nobbs, Angela H; Vickerman, M Margaret; Jenkinson, Howard F (2010) Heterologous expression of Candida albicans cell wall-associated adhesins in Saccharomyces cerevisiae Reveals differential specificities in adherence and biofilm formation and in binding oral Streptococcus gordonii. Eukaryot Cell 9:1622-34

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