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Chapter 12 : Candida albicans Colonization and Community Development
Category: Genomics and Bioinformatics
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Catheters and other prostheses provide novel surfaces for colonization by Candida albicans and other microorganisms and the formation of biofilms. The polyene and azole antifungal compounds, such as amphotericin B and fluconazole, are principal agents used to treat subjects with various Candida infections. It is well established that microorganisms colonizing surfaces grow as biofilm communities. Bcr1 regulates expression of the glycosylphosphatidylinositol (GPI)-anchored adhesins Als1, Als3, and Hwp1, which contribute to biofilm formation. These proteins promote fungal-cell-to-fungal-cell interactions in biofilm formation, with Hwp1 binding to Als1 and Als3. These developments in understanding the mechanisms of biofilm formation by C. albicans have evolved directly through applications of genomic sequence information. The availability of the C. albicans genome sequence has facilitated genome-wide bioinformatics analysis to predict every protein that may be modified by the addition of a GPI anchor. Most colonizing microorganisms on mucosal surfaces have to survive in mixed microbial communities. There are three steps in the initiation of disease by C. albicans: (i) establishment within a mixed-species community, (ii) outgrowth of C. albicans, and (iii) infection of tissues. It is hypothesized that the ability of oral streptococci and C.albicans to engage in physical and chemical communication promotes the colonization of C.albicans in the oral cavity and the development of mixed-species communities of bacteria and fungi. C.albicans is a highly successful colonizer of humans and may exist in a carriage state at mucosal surfaces in the gastrointestinal (GI) and genitourinary tracts.
Cell wall structure of C. albicans. The main structural components of the cell wall are chitin [poly-β-(1,4)-N-acetylglucosamine] (C) and β-(1,3)-glucan (G). The outer layers are composed of mannan (M) and cell wall proteins (cross-hatched irregular shapes). These are attached to the cell wall via GPI remnants to β-(1-6)-glucan (dotted lines) or retained within the cell wall noncovalently. Mannoproteins may be linked through alkali-sensitive bonds to β-(1,3)-glucan. Abbreviations: SA, surface-associated proteins, e.g., Pra1p and Bgl2p; GPI, GPI-anchored proteins, e.g., Eap1p and Als3p. Two examples of membrane integral proteins are shown, transporter (T) and sensor (S).
Intermicrobial interactions in the formation of mixed-species oral cavity communities containing C. albicans. Streptococci (Strep) are considered to be the major primary colonizers of salivary pellicle-coated surfaces and of mucosal surfaces. C. albicans can adhere to salivary or cell membrane receptors and may interact with deposited streptococci in a bimodal or multimodal mechanism. C. albicans recognizes receptor polysaccharides on the streptococci, while the latter interact with cell wall glycoproteins of C. albicans. Actinomyces naeslundii organisms are densely fimbriated, and the fimbriae recognize streptococcal receptor polysaccharides, while an unknown C. albicans adhesin recognizes A. naeslundii. Fusobacterium nucleatum recognizes both Actinomyces and streptococci, and it binds to C. albicans in a mannose-sensitive interaction involving a protein adhesin or adhesins present on the bacteria. Lactobacilli are often found in association with C. albicans ( 9 ), but cell-cell interaction mechanisms of these organisms have not yet been investigated.
C. albicans gene regulators involved in morphogenesis and biofilm formation
Some C. albicans proteins or genes involved in adhesion and invasion