Interactions of Candida tropicalis pH-related antigen 1 with complement proteins C3, C3b,factor-H,C4BP and complement evasion |
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| Affiliation: | 1. Faculty of Health & Life Sciences, De Montfort University, UK;2. Department of Respiratory Sciences, University of Leicester, UK;3. Department of Veterinary Medicine, U.A.E. University, Al Ain, United Arab Emirates;1. Division of Infectious Diseases and Division of Computer Aided Drug Design, The Red-Green Research Centre, BICCB, 16 Tejkunipara, Tejgaon, Dhaka 1215, Bangladesh;2. Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh;3. Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA;4. Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh;5. Department of Chemistry and Biochemistry, Kennesaw State University, 370 Paulding Avenue NW, Kennesaw, GA 30144, USA;1. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China;2. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China;1. Tianjin Medical University, Tianjin 300070, China;2. Department of Tissue Repair and Regeneration, PLA General Hospital and PLA Medical College, Beijing 100853, China;4. PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing 100048, China;5. Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing 100048, China;6. Plastic and Maxillofacial Surgery Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;1. Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;2. Department of Otorhinolaryngology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;3. Department of Pathology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;4. Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;1. Division of Immunology and Microbiology, Javakhishvili Tbilisi State University, Georgia;2. Tbilisi Medical Academy, Georgia;3. School of Life Sciences, University of Westminster, London, UK;4. University of Georgia, Georgia;5. IQ Clinic, Georgia |
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| Abstract: | Candida, as a part of the human microbiota, can cause opportunistic infections that are either localised or systemic candidiasis. Emerging resistance to the standard antifungal drugs is associated with increased mortality rate due to invasive Candida infections, particularly in immunocompromised patients. While there are several species of Candida, an increasing number of Candida tropicalis isolates have been recently reported from patients with invasive candidiasis or inflammatory bowel diseases. In order to establish infections, C. tropicalis has to adopt several strategies to escape the host immune attack. Understanding the immune evasion strategies is of great importance as these can be exploited as novel therapeutic targets. C. albicans pH-related antigen 1 (CaPra1), a surface bound and secretory protein, has been found to interact strongly with the immune system and help in complement evasion. However, the role of C. tropicalis Pra1 (CtPra1) and its interaction with the complement is not studied yet. Thus, we characterised how pH-related antigen 1 of C. tropicalis (CtPra1) interacts with some of the key complement proteins of the innate immune system. CtPra1 was recombinantly produced using a Kluyveromyces lactis yeast expression system. Recombinant CtPra1, was found to bind human C3 and C3b, central molecules of the complement pathways that are important components of the innate immune system. It was also found to bind human complement regulatory proteins factor-H and C4b-binding protein (C4BP). CtPra1-factor-H and CtPra1-C4BP interactions were found to be ionic in nature as the binding intensity affected by high sodium chloride concentrations. CtPra1 inhibited functional complement activation with different effects on classical (～20 %), lectin (～25 %) and alternative (～30 %) pathways. qPCR experiments using C. tropicalis clinical isolates (oral, blood and peritoneal fluid) revealed relatively higher levels of expression of CtPra1 gene when compared to the reference strain. Native CtPra1 was found to be expressed both as membrane-bound and secretory forms in the clinical isolates. Thus, C. tropicalis appears to be a master of immune evasion by using Pra1 protein. Further investigation using in-vivo models will help ascertain if these proteins can be novel therapeutic targets. |
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| Keywords: | Candida tropicalis pH-related antigen 1 Complement evasion |
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