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      Mechanisms of Immune Evasion and Bone Tissue Colonization that make Staphylococcus aureus the Primary Pathogen in Osteomyelitis

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          Abstract

          PURPOSE OF REVIEW:

          Staphylococcus aureus is the primary pathogen responsible for osteomyelitis, which remains a major healthcare burden. To understand its dominance, here we review the unique pathogenic mechanisms utilized by S. aureus, that enable it to cause incurable osteomyelitis.

          RECENT FINDINGS:

          Using an arsenal of toxins and virulence proteins, S. aureus kills and usurps immune cells during infection, to produce non-neutralizing pathogenic antibodies that thwart adaptive immunity. S. aureus also has specific mechanisms for distinct biofilm formation on implants, necrotic bone tissue, bone marrow and within the osteocyte-lacuno canicular networks (OLCN) of live bone. In vitro studies have also demonstrated potential for intracellular colonization of osteocytes, osteoblasts and osteoclasts.

          SUMMARY:

          S. aureus has evolved a multitude of virulence mechanisms to achieve life-long infection of bone, most notably colonization of OLCN. Targeting S. aureus proteins involved in these pathways could provide new targets for antibiotics and immunotherapies.

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          Most cited references114

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          The biofilm matrix.

          The microorganisms in biofilms live in a self-produced matrix of hydrated extracellular polymeric substances (EPS) that form their immediate environment. EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide the mechanical stability of biofilms, mediate their adhesion to surfaces and form a cohesive, three-dimensional polymer network that interconnects and transiently immobilizes biofilm cells. In addition, the biofilm matrix acts as an external digestive system by keeping extracellular enzymes close to the cells, enabling them to metabolize dissolved, colloidal and solid biopolymers. Here we describe the functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth.
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            Diabetic Foot Ulcers and Their Recurrence.

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              Osteomyelitis.

              Bone and joint infections are painful for patients and frustrating for both them and their doctors. The high success rates of antimicrobial therapy in most infectious diseases have not yet been achieved in bone and joint infections owing to the physiological and anatomical characteristics of bone. The key to successful management is early diagnosis, including bone sampling for microbiological and pathological examination to allow targeted and long-lasting antimicrobial therapy. The various types of osteomyelitis require differing medical and surgical therapeutic strategies. These types include, in order of decreasing frequency: osteomyelitis secondary to a contiguous focus of infection (after trauma, surgery, or insertion of a joint prosthesis); that secondary to vascular insufficiency (in diabetic foot infections); or that of haematogenous origin. Chronic osteomyelitis is associated with avascular necrosis of bone and formation of sequestrum (dead bone), and surgical debridement is necessary for cure in addition to antibiotic therapy. By contrast, acute osteomyelitis can respond to antibiotics alone. Generally, a multidisciplinary approach is required for success, involving expertise in orthopaedic surgery, infectious diseases, and plastic surgery, as well as vascular surgery, particularly for complex cases with soft-tissue loss.
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                Author and article information

                Journal
                101176492
                32518
                Curr Osteoporos Rep
                Curr Osteoporos Rep
                Current osteoporosis reports
                1544-1873
                1544-2241
                21 June 2020
                December 2019
                09 July 2020
                : 17
                : 6
                : 395-404
                Affiliations
                [1 ]Center for Musculoskeletal Research,
                [2 ]Department of Orthopaedics,
                [3 ]Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, NY, USA
                Author notes
                Corresponding Author: Edward M. Schwarz, Ph.D., Burton Professor of Orthopaedics, Director of Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, Phone: (585) 275-3063, FAX: (585) 276-2177, Edward_schwarz@ 123456urmc.rochester.edu
                Article
                PMC7344867 PMC7344867 7344867 nihpa1605238
                10.1007/s11914-019-00548-4
                7344867
                31721069
                a9c29062-9214-4db7-9466-280328487eec
                History
                Categories
                Article

                canalicular invasion,orthopaedic infections,immune proteome,adaptive immunity,osteomyelitis, Staphylococcus aureus

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