Bacterial virulence plays a crucial role in MRSA sepsis

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.

An anion and small molecule inhibition study of the β-carbonic anhydrase from Staphylococcus aureus

“…Staphylococcus aureus is a Gram-positive bacterium that infects nearly all host tissues in many mammalian species, including humans and livestock, causing severe morbidity and mortality 1 . It belongs to the sadly famous ESKAPE group of bacterial pathogens ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , Enterobacter spp.)…”

“…that are resistant to many clinically used antibiotics including methicillin and vancomycin 2 . As a consequence, the treatment of such infection remains particularly challenging if not impossible in severe cases 1 , 2 . Thus, there is an urgent need for new classes of antibiotics which can either inhibit the growth of these pathogens and subsequently kill them, or of compounds which can restore the sensitivity of resistant bacteria to the various classes of clinically used agents 3–5 .…”

Efficacy of celery (Apium graveolens L.) alcoholic extract against systemic methicillin-resistant Staphylococcus aureus infection in rat models

“…MRSA infections can spread systemically and cause severe organ damage. The ability of MRSA to spread in the bloodstream is due to its virulence factors [ 15 ]. MRSA exhibits several virulence factors, such as adhesive matrix molecules, biofilm, leukocidin, enzymes, and toxins [ 16 ].…”

Virulence adaption to environment promotes the age-dependent nasal colonization of Staphylococcus aureus

“…Staphylococcus aureus is a Gram-positive pathogen causing various acute and chronic diseases [ 1 ]. It is also a commensal bacterium frequently colonizing human anterior nares [ 2 ].…”