Abstract
Staphylococcus aureus is a Gram-positive pathogen capable of infecting nearly every vertebrate organ. Among these tissues, invasive infection of bone (osteomyelitis) is particularly common and induces high morbidity. Treatment of osteomyelitis is notoriously difficult and often requires debridement of diseased bone in conjunction with prolonged antibiotic treatment to resolve infection. During osteomyelitis, S. aureus forms characteristic multicellular microcolonies in distinct niches within bone. Virulence and metabolic responses within these multicellular microcolonies are coordinated, in part, by quorum sensing via the accessory gene regulator (agr) locus, which allows staphylococcal populations to produce toxins and adapt in response to bacterial density. During osteomyelitis, the Agr system significantly contributes to dysregulation of skeletal homeostasis and disease severity but may also paradoxically inhibit persistence in the host. Moreover, the Agr system is subject to complex crosstalk with other S. aureus regulatory systems, including SaeRS and SrrAB, which can significantly impact the progression of osteomyelitis. The objective of this review is to highlight Agr regulation, its implications on toxin production, factors that affect Agr activation, and the potential paradoxical influences of Agr regulation on disease progression during osteomyelitis.
Highlights
Osteomyelitis, or inflammation of bone, most frequently occurs as a result of bacterial infection.Staphylococcus aureus is the most commonly isolated bacterium from infectious osteomyelitis and can result in acute or chronic disease [1]
In the sections that follow, we highlight the regulatory architecture of the accessory gene regulator (Agr) system, the mechanisms of regulation of toxins related to osteomyelitis, and the impact of other regulators and two-component systems on Agr and Agr-regulated targets
Agr quorum sensing clearly contributes to the pathogenesis of S. aureus disease [13,157]
Summary
Osteomyelitis, or inflammation of bone, most frequently occurs as a result of bacterial infection. Many bacterial species, including S. aureus, possess specialized two-component systems to survey and respond to the density of genetically similar cells This process, known as quorum sensing, allows S. aureus to detect the cellular density in a given niche via production of an autoinducing peptide (AIP). The Agr system strongly contributes to staphylococcal virulence, other two-component systems and regulatory proteins, including staphylococcal accessory regulator A (SarA), catabolite control protein A (CcpA), S. aureus exoprotein expression (SaeRS), and staphylococcal respiratory response AB (SrrAB) influence virulence factor regulation. Multiple two-component systems and regulatory proteins facilitate S. aureus survival in bone and are intricately linked to Agr quorum sensing These mechanisms are discussed in more detail below. In the sections that follow, we highlight the regulatory architecture of the Agr system, the mechanisms of regulation of toxins related to osteomyelitis, and the impact of other regulators and two-component systems on Agr and Agr-regulated targets
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
