Factors Influencing the Colonization and Pathogenesis of Candida albicans in the Gut

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 10897

Special Issue Editor


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Guest Editor
Midwestern University, College of Veterinary Medicine, Glendale, Arizona
Interests: Candida albicans; Gut colonization and Pathogenesis; Therapeutics

Special Issue Information

Dear Colleagues,

Candida albicans, an opportunistic fungal pathogen present in the gastrointestinal (GI) of humans, is harmless to immunocompetent hosts with intact gut microbiota. However, administration of antibiotics and chemotherapeutic agents increases the risk of C. albicans infections by increasing the frequency and magnitude of GI colonization by C. albicans, and the source of systemic infection is often confirmed to be the GI tract. This new Special Issue of Pathogens will explore topics related to colonization and pathogenesis of C. albicans in the gut. We welcome submissions on all aspects of C. albicans related to commensalism, morphogenesis, virulence, pathogenesis, and treatment strategies within the context of the GI tract. We invite you to submit research and review articles related to these topics, and we look forward to your contribution.

Dr. Shankar Thangamani
Guest Editor

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Published Papers (4 papers)

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Research

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15 pages, 1519 KiB  
Article
In Vitro Exploration of Probiotic Bacteria Interactions with Candida Using Culture Techniques to Model Dysbiotic Conditions in Colonized Tissues
by Emma Wittman, Neela Yar, Francesco De Seta and Bryan Larsen
Pathogens 2021, 10(3), 289; https://doi.org/10.3390/pathogens10030289 - 3 Mar 2021
Cited by 2 | Viewed by 2416
Abstract
Candida albicans overgrowth at various mucosal sites is an ongoing and complex clinical concern involving interactions with indigenous microbiota and therapeutic or preventive measures superimposed on the pathogen-microbiome interaction. In this paper we describe the use of quantitative flow cytometry (specific to the [...] Read more.
Candida albicans overgrowth at various mucosal sites is an ongoing and complex clinical concern involving interactions with indigenous microbiota and therapeutic or preventive measures superimposed on the pathogen-microbiome interaction. In this paper we describe the use of quantitative flow cytometry (specific to the cytometer’s sample introduction mechanism) to explore the in vitro interaction between Candida albicans, probiotic lactobacilli and a topical vaginal therapeutic. Our central hypothesis was cytometric measurements of co-cultures of yeast and bacteria could provide a useful method for exploring the dynamics of different microbial species in culture, with and without inhibitors. Two commercial products were used as exemplars for this research, a vaginal antimicrobial gel and two species of probiotic lactobacillus intended or oral administration with crystalline bovine lactoferrin to augment the vaginal gel. The cytometer forward channel height parameter distinguished yeast from bacteria in co-culture experiments in the presence of a vaginal therapeutic gel or components of its formulation including EDTA, glycogen, polydextrose as well as the host defense factor, lactoferrin. Flow cytometry showed lactobacilli influenced yeast counts in co-culture, with the technique lending itself to wide-ranging test conditions including organisms, media composition and screening of various antimicrobials. Key findings: The proprietary vaginal gel augmented the effect of lactobacilli, as did EDTA and lactoferrin. Prebiotic compounds also enhanced Candida inhibition by lactobacilli. Propidium iodide (Fluorescence channel 3) discriminated between necrotic and non-necrotic yeast and bacteria in co-cultures under various culture conditions. This research demonstrates the value of flow cytometry to evaluate the population dynamics of yeast and bacteria in co-culture using a proprietary product and its components. We discuss both the limitations of the current study and describe how methods employed here would be transferrable to the investigation of organisms present in defined cultures or at body sites colonized by fungal species and the effects of therapeutics or probiotics on Candida. Full article
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9 pages, 1838 KiB  
Article
ERG3-Encoding Sterol C5,6-DESATURASE in Candida albicans Is Required for Virulence in an Enterically Infected Invasive Candidiasis Mouse Model
by Tatsuro Hirayama, Taiga Miyazaki, Makoto Sumiyoshi, Nobuyuki Ashizawa, Takahiro Takazono, Kazuko Yamamoto, Yoshifumi Imamura, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno and Hiroshi Mukae
Pathogens 2021, 10(1), 23; https://doi.org/10.3390/pathogens10010023 - 31 Dec 2020
Cited by 6 | Viewed by 1951
Abstract
Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of [...] Read more.
Gastrointestinal colonization by Candida species is considered the main source of candidemia. The ERG3 gene in Candida albicans encodes a sterol C5,6-desaturase, which is essential for ergosterol biosynthesis. Although ERG3 inactivation shows reduced virulence in mouse models of disseminated candidiasis, the role of ERG3 in intestinal infections is unknown. Here, we infected mice with the C. albicans strains CAE3DU3 and CAF2-1, containing mutant and wild-type ERG3, respectively, and studied gut infection and colonization by these strains. We found that the CAE3DU3 strain showed reduced colonization, pathogenesis, damage to gut mucosa, and chemokine production in the mouse model of invasive candidiasis. Additionally, mice inoculated with CAE3DU3 showed lower mortality than mice inoculated with CAF2-1 (p < 0.0001). Chemokines were less induced in the gut inoculated with CAE3DU3 than in the gut inoculated with CAF2-1. Histopathologically, although the wild-type gene was associated with a higher pathogenicity and invasion of the gut mucosa and liver tissues causing remarkable tissue necrosis, the erg3/erg3 mutant was associated with a higher accumulation of cells and lower damage to surrounding tissues than wild-type ERG3. These results establish that the ergosterol biosynthetic pathway may be associated with C. albicans gut colonization and subsequent dissemination. Full article
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Review

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15 pages, 537 KiB  
Review
Revisiting the Vital Drivers and Mechanisms of β-Glucan Masking in Human Fungal Pathogen, Candida albicans
by Saif Hameed, Sandeep Hans, Shweta Singh, Ruby Dhiman, Ross Monasky, Ramendra Pati Pandey, Shankar Thangamani and Zeeshan Fatima
Pathogens 2021, 10(8), 942; https://doi.org/10.3390/pathogens10080942 - 27 Jul 2021
Cited by 6 | Viewed by 3521
Abstract
Among the several human fungal pathogens, Candida genus represents one of the most implicated in the clinical scenario. There exist several distinctive features that govern the establishment of Candida infections in addition to their capacity to adapt to multiple stress conditions inside humans [...] Read more.
Among the several human fungal pathogens, Candida genus represents one of the most implicated in the clinical scenario. There exist several distinctive features that govern the establishment of Candida infections in addition to their capacity to adapt to multiple stress conditions inside humans which also include evasion of host immune responses. The complex fungal cell wall of the prevalent pathogen, Candida albicans, is one of the main targets of antifungal drugs and recognized by host immune cells. The wall consists of tiered arrangement of an outer thin but dense covering of mannan and inner buried layers of β-glucan and chitin. However, the pathogenic fungi adopt strategies to evade immune recognition by masking these molecules. This capacity to camouflage the immunogenic polysaccharide β-glucan from the host is a key virulence factor of C. albicans. The present review is an attempt to collate various underlying factors and mechanisms involved in Candida β-glucan masking from the available pool of knowledge and provide a comprehensive understanding. This will further improve therapeutic approaches to candidiasis by identifying new antifungal targets that blocks fungal immune evasion. Full article
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15 pages, 332 KiB  
Review
Understanding Human Microbiota Offers Novel and Promising Therapeutic Options against Candida Infections
by Saif Hameed, Sandeep Hans, Ross Monasky, Shankar Thangamani and Zeeshan Fatima
Pathogens 2021, 10(2), 183; https://doi.org/10.3390/pathogens10020183 - 9 Feb 2021
Cited by 5 | Viewed by 2387
Abstract
Human fungal pathogens particularly of Candida species are one of the major causes of hospital acquired infections in immunocompromised patients. The limited arsenal of antifungal drugs to treat Candida infections with concomitant evolution of multidrug resistant strains further complicates the management of these [...] Read more.
Human fungal pathogens particularly of Candida species are one of the major causes of hospital acquired infections in immunocompromised patients. The limited arsenal of antifungal drugs to treat Candida infections with concomitant evolution of multidrug resistant strains further complicates the management of these infections. Therefore, deployment of novel strategies to surmount the Candida infections requires immediate attention. The human body is a dynamic ecosystem having microbiota usually involving symbionts that benefit from the host, but in turn may act as commensal organisms or affect positively (mutualism) or negatively (pathogenic) the physiology and nourishment of the host. The composition of human microbiota has garnered a lot of recent attention, and despite the common occurrence of Candida spp. within the microbiota, there is still an incomplete picture of relationships between Candida spp. and other microorganism, as well as how such associations are governed. These relationships could be important to have a more holistic understanding of the human microbiota and its connection to Candida infections. Understanding the mechanisms behind commensalism and pathogenesis is vital for the development of efficient therapeutic strategies for these Candida infections. The concept of host-microbiota crosstalk plays critical roles in human health and microbiota dysbiosis and is responsible for various pathologies. Through this review, we attempted to analyze the types of human microbiota and provide an update on the current understanding in the context of health and Candida infections. The information in this article will help as a resource for development of targeted microbial therapies such as pre-/pro-biotics and microbiota transplant that has gained advantage in recent times over antibiotics and established as novel therapeutic strategy. Full article
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