The role of virulence determinants in community-associated MRSA pathogenesis

Abstract

The recent emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) marked a quantum step change in the biology and epidemiology of a major human pathogen. Various virulence determinants unique to CA-MRSA have been recently uncovered, shedding light on how these strains spread easily and sustainably among humans and frequently cause severe disease. The role of the Panton Valentine leukocidin (PVL) in CA-MRSA pathogenesis is a matter of much debate. While epidemiological data have suggested a role of PVL in the CA-MRSA disease process, recent data from relevant animal models suggest that PVL does not impact virulence of prevalent CA-MRSA strains. Identifying specialized pathogenic traits of CA-MRSA remains a challenge that will yield new diagnostic tools and therapeutic targets for drug and vaccine development.

Naphthacemycins, novel circumventors of β-lactam resistance in MRSA, produced by Streptomyces sp. KB-3346-5. II. Structure elucidation

“…The IR spectra showed they all have carbonyl (1600-1720 cm − 1 ) and hydroxyl (3350-3440 cm − 1 ) groups. UV spectra were observed at 274-280, 302-306 and 362-408 nm in the naphthacemycin A series (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), at 246-249, 287-288, 352-354 and 414-417 nm in the naphthacemycin B series (12)(13)(14)(15), and 248 and 410 nm in the naphthacemycin C series (16-17). Naphthacemycins are soluble in chloroform, ethyl acetate and methanol and insoluble in n-hexane and H 2 O.…”

“…Community-acquired MRSA has also become a serious public health issue. 1 MRSA is resistant to β-lactam antibiotics and usually resistant to most other classes of antibiotics. There are a few antibiotics used for MRSA, for example, vancomycin, teicoplanin, arbekacin, linezolid, daptomycin and tigecycline, but microorganism strains resistant to these compounds are increasingly being reported.…”

“…In the course of screening for new anti-MRSA compounds, we found cyslabdan, which enhances the activity of imipenem (a carbapenem type β-lactam antibiotic) against MRSA. 2,3 Further screening for microbial metabolites that circumvent the β-lactam resistance of MRSA led us to find the naphthacemycins A 1 -A 11 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), B 1 -B 4 (12-15) and C 1 -C 2 (16-17) (Scheme 1), reported as KB-3346-5 substances in the patent by our group, 4 from a cultured broth of Streptomyces sp. KB-3346-5.…”

Transcription of the phage-encoded Panton–Valentine leukocidin of Staphylococcus aureus is dependent on the phage life-cycle and on the host background

“…S. aureus necrotizing pneumonia and skin and soft-tissue infections, which can also affect young, immunocompetent persons, is described as a threat associated with community-acquired (ca)MRSA and MSSA strains bearing the Panton-Valentine leukocidin (PVL) genes (Diederen & Kluytmans, 2006;Gillet et al, 2002;Vandenesch et al, 2003). The possible contribution of PVL to the virulence of S. aureus has been argued in studies using a variety of different animal models (Bubeck Wardenburg et al, 2008;Diep & Otto, 2008; LabandeiraRey et al, 2007;Montgomery et al, 2008;Voyich et al, 2006;Wang et al, 2007). PVL is a bi-component, poreforming cytotoxin that targets host defence cells such as human polymorphonuclear neutrophils, monocytes and macrophages (Genestier et al, 2005;Kaneko & Kamio, 2004;Prevost et al, 1995).…”

Necrotizing Pneumonia in the Community

“…PVL is a staphylococcal toxin with a well-established cytolytic mechanism that specifically targets phagocytic leukocytes (3). However, the role of PVL in necrotizing lesion development is still controversial (9), and is probably due to the species-specific susceptibility of neutrophils to the lytic effects of PVL (10). The prevalence of the PVL genes varies geographically (3,11).…”