Mechanisms of community MRSA virulence

National Institute Of Allergy And Infectious Diseases

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Abstract

In FY2015, we investigated how bacterial pathogens such as Staphylococcus aureus cause human disease. Although most bacteria are killed readily by PMNs, some strains of S. aureus have evolved mechanisms to circumvent destruction by neutrophils and thereby cause human infections. Notably, Staphylococcus aureus is among the most frequent causes of bloodstream, skin and soft tissue, and lower respiratory tract infections in much of the world, including the United States. In addition, the pathogen has become increasingly resistant to antibiotics over the past several decades and methicillin-resistant S. aureus (MRSA) is a leading cause of healthcare-associated infections. Thus, treatment options are limited. Healthcare-associated MRSA infections are typical of individuals with predisposing risk factors. In contrast, community-associated MRSA (CA-MRSA) cause disease in otherwise healthy individuals, and these infections can be severe or fatal. CA-MRSA emerged in the 1990s and then spread worldwide over the next decade. Although there has been a recent decrease in the number of hospital MRSA infections, the level of CA-MRSA infections has remained relatively constant. The molecular basis for the increased virulence potential and success of CA-MRSA strains is incompletely defined. Thus, a significant component of the Section is directed to address this deficiency in knowledge. Inasmuch as skin and soft tissue infections (SSTIs) are the most prominent manifestation of CA-MRSA infections, we used a rabbit skin infection model to investigate changes in the S. aureus transcriptome in vivo. Our findings provided additional insight into the pathogenesis of S. aureus SSTIs, including a temporal component of the host response (Malachowa et al., PLoS ONE, 2014). Other ongoing MRSA studies investigated the 1) interaction of S. aureus with components of the human immune system, 2) the ability of influenza A virus to alter the response of neutrophils to S. aureus, and 3) the transmission and succces of MRSA in correctional facilites (collaboration with Columbia University).