In FY2016, we continued to investigate how Staphylococcus aureus causes 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. Other ongoing studies investigated the interaction of S. aureus with components of the human immune system, and the ability of influenza A virus to alter the response of neutrophils to S. aureus.

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9
Fiscal Year
2016
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Malachowa, Natalia; Freedman, Brett; Sturdevant, Daniel E et al. (2018) Differential Ability of Pandemic and Seasonal H1N1 Influenza A Viruses To Alter the Function of Human Neutrophils. mSphere 3:
Malachowa, Natalia; DeLeo, Frank R (2018) Host Response to Staphylococcus aureus Quorum Sensing Is NO. Cell Host Microbe 23:578-580
McGuinness, Will A; Malachowa, Natalia; DeLeo, Frank R (2017) Vancomycin Resistance in Staphylococcus aureus?. Yale J Biol Med 90:269-281
Kobayashi, Scott D; Malachowa, Natalia; DeLeo, Frank R (2017) Influence of Microbes on Neutrophil Life and Death. Front Cell Infect Microbiol 7:159
McGuinness, Will A; Kobayashi, Scott D; DeLeo, Frank R (2016) Evasion of Neutrophil Killing by Staphylococcus aureus. Pathogens 5:
Malachowa, Natalia; Kobayashi, Scott D; Porter, Adeline R et al. (2016) Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection. PLoS One 11:e0158293
Musser, James M; DeLeo, Frank R (2015) Molecular pathogenesis lessons from the world of infectious diseases research. Am J Pathol 185:1502-4
Greenlee-Wacker, Mallary; DeLeo, Frank R; Nauseef, William M (2015) How methicillin-resistant Staphylococcus aureus evade neutrophil killing. Curr Opin Hematol 22:30-5
Kobayashi, Scott D; Malachowa, Natalia; DeLeo, Frank R (2015) Pathogenesis of Staphylococcus aureus abscesses. Am J Pathol 185:1518-27
Malachowa, Natalia; Kobayashi, Scott D; Sturdevant, Daniel E et al. (2015) Insights into the Staphylococcus aureus-host interface: global changes in host and pathogen gene expression in a rabbit skin infection model. PLoS One 10:e0117713

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