Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox
Abstract
:1. Introduction
2. Conserved Mechanisms of Two-Component Systems Apply to Quorum-Mediated Virulence Regulation in S. aureus
3. Agr Signaling Mechanisms Regulate Toxin and Immunomodulatory Protein Production during S. aureus Osteomyelitis
3.1. Agr Signaling Components Interact to Control Virulence Genes
3.2. S. aureus Cytolytic Toxins Regulated by Agr
3.2.1. Phenol-Soluble Modulins (PSMs)
3.2.2. Alpha-Hemolysin (Hla)
3.2.3. Panton–Valentine Leukocidin (PVL)
3.3. S. aureus Immunomodulatory Molecules Regulated by Agr
3.3.1. Protein A (SpA)
3.3.2. MHC Class II Analog Protein (Map)
3.4. S. aureus Coagulases Regulated by Agr
3.4.1. Staphylocoagulase (Coa)
3.4.2. Von Willebrand Factor-Binding Protein (vWbp)
4. Regulatory Control of AIP Is Strain and Species Specific
5. S. aureus Clinical Isolates with agr Mutations
5.1. Characteristic S. aureus agr Mutations Are Isolated from Patients with Chronic Infection and Have the Ability to Revert to Wildtype
5.2. Agr Expression Is Temporally Regulated to Promote S. aureus Adhesion and Toxin Production at Distinct Phases of Infection
5.3. The Agr System Has Paradoxical Effects during Infection
6. Environmental Factors Influence S. aureus Agr Regulation Through Crosstalk with Global Regulators
6.1. Staphylococcal Respiratory Response AB (SrrAB) Senses and Responds to Changes in Cellular Redox
6.2. Staphylococcal Accessory Regulator A (SarA) Is a Critical Global Regulator that Crosstalks with the Agr System and Contributes to Osteomyelitis Pathogenesis
6.3. The S. aureus Exoprotein Expression (SaeRS) Two-Component System Regulates Proteases that Influence Osteomyelitis-Associated Bone Destruction
6.4. Metabolite-Responsive Transcription Factors Regulate S. aureus Metabolism and Virulence
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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---|---|---|---|
Gillaspy, A.F. et al. [46] | 1995 | Rabbit | Agr increases osteomyelitis incidence and severity, but inactivation of agr does not inhibit S. aureus colonization of bone. |
Blevins, J.S. et al. [47] | 2003 | Mouse | Agr mutation decreases osteomyelitis pathology scores, including number of abscesses, physis destruction, and histological inflammation. |
Cassat, J.E. et al. [7] | 2013 | Mouse | Inactivation of agr decreases bone destruction, and Agr-regulated α-type PSM production contributes to bone destruction during S. aureus infection. |
Hendrix, A.S. et al. [48] | 2016 | Mouse | Pharmacologic blockade of Agr signaling reduces osteomyelitis pathogenesis. |
Wilde, A.D. et al. [26] | 2015 | Mouse | Agr-regulated PSM production is influenced by hypoxia and signaling through SrrAB during osteomyelitis. |
Bouras, D. et al. [49] | 2018 | Human | Clinical pediatric methicillin resistant S. aureus (MRSA) isolates primarily contained agr-III systems. |
Krishna Mannala, G. et al. [50] | 2018 | Human | A low-virulent clinical S. aureus bone isolate harbors frameshift mutations in the agrC gene. |
Suligoy, C.M. et al. [21] | 2018 | Mouse | Lack of Agr-dependent factors decrease S. aureus virulence during chronic osteomyelitis while permitting adaptation for persistence. |
Masters, E.A. et al. [51] | 2019 | Murine and in vitro | A S. aureus agr mutant retains its ability to invade the osteocyte lacuno-canalicular network of cortical bone. |
Kwiecinski, J.M. et al. [52] | 2019 | Human | S. aureus agr type from clinical invasive infections correlates with biofilm formation. |
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Butrico, C.E.; Cassat, J.E. Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox. Toxins 2020, 12, 516. https://doi.org/10.3390/toxins12080516
Butrico CE, Cassat JE. Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox. Toxins. 2020; 12(8):516. https://doi.org/10.3390/toxins12080516
Chicago/Turabian StyleButrico, Casey E., and James E. Cassat. 2020. "Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox" Toxins 12, no. 8: 516. https://doi.org/10.3390/toxins12080516
APA StyleButrico, C. E., & Cassat, J. E. (2020). Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox. Toxins, 12(8), 516. https://doi.org/10.3390/toxins12080516