A Prospective Investigation of Outcomes after Hospital Discharge for Endemic, Community-Acquired Methicillin-Resistant and -Susceptible Staphylococcus aureus Skin Infection

Miller, Loren G.; Quan, Clifford; Shay, Anthony; Mostafaie, Katayoun; Bharadwa, Kiran; Tan, Nelly; Matayoshi, Kelli; Cronin, J.; Tan, Jennifer; Tagudar, G.; Bayer, Arnold S.

doi:10.1086/511041

Cited by 137 publications

(101 citation statements)

References 29 publications

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“…5). This finding confirms that methicillin resistance does not have an impact on virulence, as shown recently in the USA300 and USA400 clones (12,13,28) and is consistent with reports on comparable clinical outcomes observed in CA-MRSA and CA-MSSA strains (29)(30)(31). Finally, we did not detect significant differences in PSM␣3 expression between carriage vs. infection isolates, indicating that high expression of this key virulence determinant is not selected for in strains causing disease but is a general characteristic of the USA300/USA500 sublineage.…”

Section: Sequential Acquisition Of Virulence Genes By Contemporary Cc8supporting

confidence: 92%

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Diep

Villaruz

et al. 2009

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

361

373

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Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged worldwide. The United States, in particular, is experiencing a serious epidemic of CA-MRSA that is almost entirely caused by an extraordinarily infectious strain named USA300. However, the molecular determinants underlying the pathogenic success of CA-MRSA are mostly unknown. To gain insight into the evolution of the exceptional potential of USA300 to cause disease, we compared the phylogeny and virulence of USA300 with that of closely related MRSA clones. We discovered that the sublineage from which USA300 evolved is characterized by a phenotype of high virulence that is clearly distinct from other MRSA strains. Namely, USA300 and its progenitor, USA500, had high virulence in animal infection models and the capacity to evade innate host defense mechanisms. Furthermore, our results indicate that increased virulence in the USA300/USA500 sublineage is attributable to differential expression of core genome-encoded virulence determinants, such as phenol-soluble modulins and ␣-toxin. Notably, the fact that the virulence phenotype of USA300 was already established in its progenitor indicates that acquisition of mobile genetic elements has played a limited role in the evolution of USA300 virulence and points to a possibly different role of those elements. Thus, our results highlight the importance of differential gene expression in the evolution of USA300 virulence. This finding calls for a profound revision of our notion about CA-MRSA pathogenesis at the molecular level and has important implications for design of therapeutics directed against CA-MRSA.

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Section: Sequential Acquisition Of Virulence Genes By Contemporary Cc8supporting

confidence: 92%

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Diep

Villaruz

et al. 2009

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

361

373

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“…Of note, other infectious diseases, such as Dengue hemorrhagic fever, have been proposed to have an antibody-dependent enhancement of pathogenesis (34). The findings from our animal studies, along with the high recurrence rate of MRSA infections in humans, often involving the same strain (22)(23)(24)(25)35), and the increased antibody levels to PVL reported after a primary infection (26,27), suggest the need for caution when considering the value of immunization against PVL, due to the potential of antibody to enhance virulence in at least some common settings of S. aureus infection. Susceptibility of PVL + and isogenic Δpvl S. aureus strains to the antimicrobial activity of PMNs.…”

Section: Discussionsupporting

confidence: 55%

“…Importantly, in this setting, antibody to PVL appeared to decrease the ability of PMNs to control the proliferation of PVLproducing S. aureus, possibly by impairing the process through which these immune cells are activated. These findings likely are highly applicable to human infections with MRSA, given that a 30%-50% recurrence rate within 18 months of MRSA infection has been reported in previously infected humans, usually with the same strain (22)(23)(24)(25), and that individuals with PVL-positive MRSA infections mount potent immune responses to PVL following primary infections (26,27). This finding suggests that humans with recurrent PVL + MRSA infections likely have very high levels of antibody at the onset of infection that nonetheless does nothing to prevent recurrent infection and might even promote reinfection.…”

Section: Discussionmentioning

confidence: 77%

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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“…Among adults, CA-MRSA has been associated with risk factors including injection drug use [6], homelessness [7], incarceration, and visiting bars and raves [8]. Outbreaks have also occurred among athletes [9], military recruits [10], and men who have sex with men [11].…”

mentioning

confidence: 99%

Epidemiologic Similarities in Pediatric Community-Associated Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus in the San Francisco Bay Area

Hsiang

Shiau

Nadle³

et al. 2012

Journal of the Pediatric Infectious Diseases Society

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A Prospective Investigation of Outcomes after Hospital Discharge for Endemic, Community-Acquired Methicillin-Resistant and -Susceptible Staphylococcus aureus Skin Infection

Cited by 137 publications

References 29 publications

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

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

Epidemiologic Similarities in Pediatric Community-Associated Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus in the San Francisco Bay Area

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