Bacterial Two-component and Hetero-heptameric Pore-forming Cytolytic Toxins: Structures, Pore-forming Mechanism, and Organization of the Genes

Kaneko, Jun; Kamio, Yoshiyuki

doi:10.1271/bbb.68.981

Cited by 296 publications

(266 citation statements)

References 73 publications

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“…These results suggest that antibody to PVL interferes with host defenses that contribute to controlling bacterial levels, allowing PVL-producing S. aureus strains to replicate more efficiently within mouse abscesses. Because antisera to S. aureus leukocidins are crossreactive (10), and because the Δpvl S. aureus strains may make additional leukocidins, such as LukD/LukE and gamma hemolysin, we next examined whether the effect of the antiserum to PVL was specific to this microbial factor by injecting mice with either nonimmune or PVL-immune rabbit antisera before infection with Δpvl S. aureus strains. In this setting, there were no differences in the cfu counts recovered form the abscesses of mice given nonimmune or PVL-immune antisera (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Successful deletion of the pvl genes (Δpvl) was confirmed by PCR and Western blot analysis for protein production (Fig. S5); the lower protein band that remains in Δpvl samples can be attributed to cross-reactive staphylococcal leukocidin(s) (10). The SF8300 strain, along with LAC and its isogenic Δpvl counterpart (LAC Δpvl), were provided by M. Otto.…”

Section: Methodsmentioning

confidence: 93%

“…Production of the Panton-Valentine leukocidin (PVL) is a characteristic of CA-MRSA strains (4), but PVL's contribution to pathogenesis of S. aureus is controversial (6)(7)(8)(9). PVL is a bicomponent pore-forming toxin composed of the LukF and LukS proteins encoded by the corresponding genes present in tandem on a bacteriophage lysogenized within the S. aureus chromosome (10). Previous work with these types of toxins has shown that they can lyse polymorphonuclear neutrophils (PMNs) and monocytes of the white blood cell lineage (11,12); however, importantly, at sublytic levels, staphylococcal leukocidins also have a strong proinflammatory effect on granulocytes (12).…”

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confidence: 99%

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Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection

Yoong

Pier

2010

Proc. Natl. Acad. Sci. U.S.A.

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Community-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) expressing the Panton-Valentine leukocidin (PVL) are rampant, but the contribution of PVL to bacterial virulence remains controversial. While PVL is usually viewed as a cytotoxin, at sublytic amounts it activates protective innate immune responses. A leukotoxic effect might predominate in high inoculum studies, whereas protective proinflammatory properties might predominate in settings with lower bacterial inocula that more closely mimic what initially occurs in humans. However, these protective effects might possibly be neutralized by antibodies to PVL, which are found in normal human sera and at increased levels following PVL + S. aureus infections. In a low-inoculum murine skin abscess model including a foreign body at the infection site, strains deleted for the pvl genes replicated more efficiently within abscesses than isogenic PVL + strains. Coinfection of mice at separate sites with isogenic PVL + and PVL -MRSA abrogated the differences in bacterial burdens, indicating a systemic effect on host innate immunity from production of PVL. Mice given antibody to PVL and then infected with seven different PVL + strains also had significantly higher bacterial counts in abscesses compared with mice given nonimmune serum. Antibody to PVL had no effect on MRSA strains that did not produce PVL. In vitro, antibody to PVL incapacitated PVL-mediated activation of PMNs, indicating that virulence of PVL + MRSA is enhanced by the interference of PVL-activated innate immune responses. Given the high rates of primary and recurring MRSA infections in humans, it appears that antibodies to PVL might contribute to host susceptibility to infection.bacterial pathogenesis | immunity | Panton-Valentine leukocidin | MRSA

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 93%

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confidence: 99%

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Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection

Yoong

Pier

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…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). The active form of PVL requires the assembly of two polypeptides, LukS-PV and LukF-PV, for which the corresponding genes (lukS-PV, lukF-PV) are carried by a prophage.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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Panton-Valentine leukocidin (PVL) is a pore-forming, bi-component toxin secreted by Staphylococcus aureus strains epidemiologically associated with diseases such as necrotizing pneumonia and skin and soft-tissue infections. Here we demonstrate that transcription of the phage-encoded PVL (encoded in the luk-PV operon) is dependent on two major determinants: the phage life-cycle and the host chromosomal background. Mitomycin C induction of PVLencoding prophages from different community-acquired MRSA strains led to an increase in the amount of luk-PV mRNA as a result of read-through transcription from latent phage promoters and an increase in phage copy numbers. Failing prophage excision was reflected in a constant expression of luk-PV as in the case of strain USA300, suggesting that wSa2USA300 is a replication-defective prophage. Additionally, we could show that luk-PV transcription is influenced by the S. aureus global virulence regulators agr and sae. We found a strong impact of the host background on prophage induction and replication when analysing PVL phages in different S. aureus strains. For example phage wSa2mw was greatly induced by mitomycin C in its native host MW2 and in strain Newman but to a considerably lesser extent in strains 8325-4, RN6390 and ISP479c. This discrepancy was not linked to the SOS response of the bacteria since recA transcription did not vary between the strains. These results suggest a fine tuning between certain phages and their host, with major impact on the expression of phage-encoded virulence genes. INTRODUCTIONStaphylococcus aureus causes a variety of local and systemic infections in humans and is one of the most important community-acquired and nosocomial pathogens. The versatility of this bacterium is due to its ability to produce a wide range of surface-exposed molecules which mediate interaction with the host cell, as well as several secreted virulence factors. 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). The active form of PVL requires the assembly of two polypeptides, LukS-PV and LukF-PV, for which the corresponding genes (lukS-PV, lukF-PV) are carried by a prophage.Although tightly linked to the phage genome and dependent on it for horizontal transfer, most of the phage-encoded virulence factors are i...

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“…We then consider the case of a highly incompressible, but purely viscous membrane of varying porosity. Such systems are reminiscent of giant unilamellar vesicles (GUVs) [14,15,16] containing pore-forming proteins [17,18,19].…”

Section: Introductionmentioning

confidence: 99%

Nanorheology of viscoelastic shells: Applications to viral capsids

Kuriabova

Levine

2008

Phys. Rev. E

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We study the microrheology of nanoparticle shells [Dinsmore et al. Science 298, 1006(2002] and viral capsids [Ivanovska et al. PNAS 101, 7600 (2004)] by computing the mechanical response function and thermal fluctuation spectrum of a viscoelastic spherical shell that is permeable to the surrounding solvent. We determine analytically the damped dynamics of the shear, bend, and compression modes of the shell coupled to the solvent both inside and outside the sphere in the zero Reynolds number limit. We identify fundamental length and time scales in the system, and compute the thermal correlation function of displacements of antipodal points on the sphere and the mechanical response to pinching forces applied at these points. We describe how such a frequency-dependent antipodal correlation and/or response function, which should be measurable in new AFM-based microrheology experiments, can probe the viscoelasticity of these synthetic and biological shells constructed of nanoparticles.

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Bacterial Two-component and Hetero-heptameric Pore-forming Cytolytic Toxins: Structures, Pore-forming Mechanism, and Organization of the Genes

Cited by 296 publications

References 73 publications

Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection

Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection

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

Nanorheology of viscoelastic shells: Applications to viral capsids

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