Silverman RJ, Nobbs AH, Vickerman MM, Barbour ME, Jenkinson HF.. Interaction of Candida albicans cell wall Als3 protein with Streptococcus gordonii SspB adhesin promotes development of mixed-species communities. Infect Immun 78: 4644-4652

School of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom.
Infection and immunity (Impact Factor: 3.73). 11/2010; 78(11):4644-52. DOI: 10.1128/IAI.00685-10
Source: PubMed


Candida albicans colonizes human mucosa and prosthetic surfaces associated with artificial joints, catheters, and dentures. In the oral cavity, C. albicans coexists with numerous bacterial species, and evidence suggests that bacteria may modulate fungal growth and biofilm formation. Streptococcus gordonii is found on most oral cavity surfaces and interacts with C. albicans to promote hyphal and biofilm formation. In this study, we investigated the role of the hyphal-wall protein Als3p in interactions of C. albicans with S. gordonii. Utilizing an ALS3 deletion mutant strain, it was shown that cells were not affected in initial adherence to the salivary pellicle or in hyphal formation in the planktonic phase. However, the Als3(-) mutant was unable to form biofilms on the salivary pellicle or deposited S. gordonii DL1 wild-type cells, and after initial adherence, als3Δ/als3Δ (ΔALS3) cells became detached concomitant with hyphal formation. In coaggregation assays, S. gordonii cells attached to, and accumulated around, hyphae formed by C. albicans wild-type cells. However, streptococci failed to attach to hyphae produced by the ΔALS3 mutant. Saccharomyces cerevisiae S150-2B cells expressing Als3p, but not control cells, supported binding of S. gordonii DL1. However, S. gordonii Δ(sspA sspB) cells deficient in production of the surface protein adhesins SspA and SspB showed >50% reduced levels of binding to S. cerevisiae expressing Als3p. Lactococcus lactis cells expressing SspB bound avidly to S. cerevisiae expressing Als3p, but not to S150-2B wild-type cells. These results show that recognition of C. albicans by S. gordonii involves Als3 protein-SspB protein interaction, defining a novel mechanism in fungal-bacterial communication.

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    • "Furthermore, microscopic studies have revealed corn-cob-like structures formed by Candida and streptococci in the mouth of humans (Zijnge et al., 2010). In vitro studies have also shown that Candida and streptococci physically interact via specific adhesin-receptor mediated binding forming biofilm structures on abiotic surfaces (Silverman et al., 2010). Collectively this evidence supports the idea that Candida and streptococci may form a potentially mutualistic partnership. "
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    ABSTRACT: High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.
    Frontiers in Cellular and Infection Microbiology 07/2014; 4:101. DOI:10.3389/fcimb.2014.00101 · 3.72 Impact Factor
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    • "Candida infections can be superficial or systemic, including, respectively oral thrush and often-fatal candidemias [15]. Additionally, C. albicans forms mixed fungal-bacterial biofilms with increased resistance to antifungals and antibacterials [16]–[19]. The ability of this fungus to aggregate, adhere to host cells, form biofilms, and even modulate the host response is attributed to amyloid-forming adhesion proteins belonging to the Als adhesin family [7], [20]–[24]. "
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    ABSTRACT: Many fungal cell adhesion proteins form functional amyloid patches on the surface of adhering cells. The Candida albicans Agglutinin-like sequence (Als) adhesins are exemplars for this phenomenon, and have amyloid forming sequences that are conserved between family members. The Als5p amyloid sequence mediates amyloid fibril formation and is critical for cell adhesion and biofilm formation, and is also present in the related adhesins Als1p and Als3p. We have developed a fluorescent peptide probe containing the conserved Als amyloid-forming sequence. This peptide bound specifically to yeast expressing Als5p, but not to cells lacking the adhesin. The probe bound to both yeast and hyphal forms of C. albicans. Δals1/Δals3 single and double deletion strains exhibited reduced fluorescence, indicating that probe binding required expression of these proteins. Additionally, the Als peptide specifically stained fungal cells in abscesses in autopsy sections. Counterstaining with calcofluor white showed colocalization with the amyloid peptide. In addition, fungi in autopsy sections derived from the gastrointestinal tract showed colocalization of the amyloid-specific dye thioflavin T and the fluorescent peptide. Collectively, our data demonstrate that we can exploit amyloid sequence specificity for detection of functional amyloids in situ.
    PLoS ONE 01/2014; 9(1):e86067. DOI:10.1371/journal.pone.0086067 · 3.23 Impact Factor
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    • "To identify the CWPs on C. albicans involved, Nobbs et al. screened a panel of C. albicans CWPs for adhesion to biotic and abiotic surfaces and bacteria including S. gordonii and found that Als3, Eap1, and Hwp1 were able to enhance binding to S. gordonii (Nobbs et al., 2010) with the most important role for Als3. Further evidence suggested that SspB is the main bacterial ligand for this receptor and that both Als3 and SspB have amyloid properties, providing a model of adherence between both proteins (Silverman et al., 2010). Another important bacterial pathogen is S. aureus, which is associated with severe disease and high mortality (Harriott & Noverr, 2009). "
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    ABSTRACT: A considerable number of infectious diseases involve multiple microbial species coexisting and interacting in a host. Only recently however the impact of these polymicrobial diseases has been appreciated and investigated. Often, the causative microbial species are embedded in an extracellular matrix forming biofilms, a form of existence that offers protection against chemotherapeutic agents and host immune defenses. Therefore, recent efforts have focused on developing novel therapeutic strategies targeting biofilm-associated polymicrobial infections, a task which has proved to be challenging. One promising approach to inhibit the development of such complex infections is to impede the interactions between the microbial species via inhibition of adhesion. To that end, studies have focused on identifying specific cell wall adhesins and receptors involved in the interactions between the various bacterial species and the most pathogenic human fungal species Candida albicans. This review highlights the important findings from these studies and describes the available tools and techniques that have provided insights into the role of secreted molecules orchestrating microbial interactions in biofilms. Specifically, we focus on the interactions that take place in oral biofilms and the implications of these interactions on oral health and therapeutic strategies. This article is protected by copyright. All rights reserved.
    Pathogens and Disease 12/2013; 70(3). DOI:10.1111/2049-632X.12123 · 2.40 Impact Factor
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