1. Bacterial virulence plays a crucial role in MRSA sepsis.
- Author
-
Cheung GYC, Bae JS, Liu R, Hunt RL, Zheng Y, and Otto M
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Bacterial Proteins metabolism, Catheter-Related Infections complications, Catheter-Related Infections drug therapy, Catheter-Related Infections microbiology, Female, Leukopenia etiology, Leukopenia pathology, Mice, Mice, Inbred C57BL, Rabbits, Sepsis drug therapy, Sepsis microbiology, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Virulence Factors genetics, Virulence Factors metabolism, Drug Resistance, Microbial, Leukopenia diagnosis, Methicillin-Resistant Staphylococcus aureus pathogenicity, Quorum Sensing, Sepsis complications, Staphylococcal Infections complications, Virulence
- Abstract
Bacterial sepsis is a major global cause of death. However, the pathophysiology of sepsis has remained poorly understood. In industrialized nations, Staphylococcus aureus represents the pathogen most commonly associated with mortality due to sepsis. Because of the alarming spread of antibiotic resistance, anti-virulence strategies are often proposed to treat staphylococcal sepsis. However, we do not yet completely understand if and how bacterial virulence contributes to sepsis, which is vital for a thorough assessment of such strategies. We here examined the role of virulence and quorum-sensing regulation in mouse and rabbit models of sepsis caused by methicillin-resistant S. aureus (MRSA). We determined that leukopenia was a predictor of disease outcome during an early critical stage of sepsis. Furthermore, in device-associated infection as the most frequent type of staphylococcal blood infection, quorum-sensing deficiency resulted in significantly higher mortality. Our findings give important guidance regarding anti-virulence drug development strategies for the treatment of staphylococcal sepsis. Moreover, they considerably add to our understanding of how bacterial sepsis develops by revealing a critical early stage of infection during which the battle between bacteria and leukocytes determines sepsis outcome. While sepsis has traditionally been attributed mainly to host factors, our study highlights a key role of the invading pathogen and its virulence mechanisms., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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