In 2012, a primary focus of research in my laboratory investigated how bacterial pathogens such as Staphylococcus aureus cause human disease. Although most bacteria are killed readily by PMNs, certain strains of S. aureus have evolved mechanisms to circumvent destruction by neutrophils and thereby cause human infections. Notably, S. aureus is the most frequent etiologic agent causing bloodstream infection, skin and soft tissue infection, and lower respiratory tract infection in much of the world, including the United States. In addition, the pathogen has become increasingly resistant to antibiotics over the past few decades and methicillin-resistant S. aureus (MRSA) is a leading cause of hospital-acquired infections. Thus, treatment options are limited. Hospital-acquired MRSA infections are also typical of individuals with predisposing risk factors. In contrast, community-associated (or acquired) MRSA (CA-MRSA) cause disease in otherwise healthy individuals, and these infections can be severe/fatal. There has been a relatively high number of CA-MRSA infections worldwide, and this includes an ongoing epidemic of CA-MRSA infections in the United States. The molecular basis for the increased incidence and severity of CA-MRSA disease is not known. We hypothesize that the ability of bacteria to cause disease is largely due to pathogen-derived factors that alter normal neutrophil function and individual host susceptibility. Therefore, a better understanding of the bacteria-PMN interface at the cell and molecular levels will provide information critical to our understanding, treatment, and control of disease caused by bacterial pathogens. S. aureus is an ideal model pathogen with which to test our hypothesis because it is an important cause of human disease, it can be multi-drug resistant and thus hard to eradicate, and neutrophils are the first line of defense against S. aureus infections. To date, our studies include identification of genes and proteins used by CA-MRSA to evade destruction by human neutrophils, hence contributing to virulence, survival and pathogenesis.
| 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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