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Microbes & Immunity





                                        REVIEW ARTICLE
                                        Staphylococcus aureus capsule: Production,

                                        function, and regulation



                                        Yifan Rao 1  , Zuwen Guo 2  , Huagang Peng 2  , Xiancai Rao * , and
                                                                                           2
                                        Guixue Wang *
                                                   1,3
                                        1 Key Laboratory of Biorheological and Technology of the Ministry of Education, State and Local Joint
                                        Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at
                                        Bioengineering College of Chongqing University, Chongqing, China
                                        2 Department of Microbiology, College of Basic Medical Sciences, Key Laboratory of Microbial
                                        Engineering under the Educational Committee in Chongqing, Army Medical University (Third Military
                                        Medical University), Chongqing, China
                                        3 Jinfeng Laboratory, Chongqing, China



                                        Abstract

                                        Staphylococcus  aureus is a major opportunistic pathogen that causes a wide
                                        spectrum of human and animal diseases. Capsule is one of the key virulence factors of
                                        S. aureus. Approximately 90% of S. aureus isolates produce capsular polysaccharides
                                        (CPs) that envelop the entire bacterial cells. CPs can suppress the phagocytosis of
                                        S. aureus  by innate immune cells, promote intracellular survival, and reduce the
                                        killing efficacy of antimicrobial agents. As a result, CPs are versatile candidates for
                                        vaccine development. The synthesis of S. aureus CPs is controlled by the cap operon,
            *Corresponding authors:
            Xiancai Rao                 which contains 16 genes encoding functional enzymes involved in the biosynthesis
            (xcrao@tmmu.edu.cn)         and  transport  of  CPs.  During  S. aureus  growth,  cap  operon  expression  is  strictly
            Guixue Wang                 regulated. The control region of the cap operon is characterized by two promoters:
            (wanggx@cqu.edu.cn)
                                        a housekeeping sigma factor A (SigA)-dependent promoter and a stress-responsive
            Citation: Rao Y, Guo Z, Peng H,   sigma factor B-dependent promoter. Many transcription factors, including both
            Rao X, Wang G. Staphylococcus
            aureus capsule: Production,   positive and negative regulatory molecules, are timely involved in the regulatory
            function, and regulation. Microbes &   network of S. aureus capsule synthesis. Moreover, environmental conditions such as
            Immunity. 2025;2(4):1-16.   medium composition and carbon dioxide levels further modulate CP production.
            doi: 10.36922/mi.8392
                                        In this review, the structure and function of S. aureus CPs are introduced, and the
            Received: January 3, 2025   biosynthesis of S. aureus CPs is discussed. Moreover, the regulation of S. aureus CP
            Revised: April 9, 2025      production is summarized, the factors affecting CP production are outlined, and the
                                        preparation of S. aureus CPs is reviewed. The advanced information presented here
            Accepted: April 15, 2025
                                        may provide useful references for further research on the production and function of
            Published online: May 2, 2025  S. aureus CPs.
            Copyright: © 2025 Author(s).
            This is an Open-Access article
            distributed under the terms of the   Keywords: Staphylococcus aureus; Capsular polysaccharides; Immune evasion; Cap
            Creative Commons Attribution   operon; Virulence factors; Capsule purification
            License, permitting distribution,
            and reproduction in any medium,
            provided the original work is
            properly cited.
                                        1. Introduction
            Publisher’s Note: AccScience
            Publishing remains neutral with   Staphylococcus  aureus is a Gram-positive opportunistic pathogen that commonly
            regard to jurisdictional claims in                                                         1
            published maps and institutional   colonizes the skin, nasopharynx, and mucosal surfaces of healthy individuals.  Under
            affiliations.               conditions  of immune suppression or  epithelial  barrier  disruption,  S. aureus can


            Volume 2 Issue 4 (2025)                         1                                doi: 10.36922/mi.8392
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