In FY2014, a primary focus of research in my laboratory (Section) 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. For example, we recently identified a novel S. aureus bi-component leukotoxin (leukotoxin GH, LukGH) and continue to investigate its role in bacterial virulence. We found that LukGH promoted release of neutrophil extracellular traps (NETs), which in turn, ensnared but did not kill S. aureus (Malachowa et al., J Immunol, 2014). Furthermore, we found that electropermeabilization of human neutrophils--used as a separate means to create pores in the neutrophil plasma membrane--similarly induced formation of NETs, a finding consistent with the notion that NETs can form during non-specific cytolysis. Thus, the ability of LukGH to promote formation of NETs likely contributes to the inflammatory response and host defense against S. aureus infection. Studies done in collaboration with William Nauseef, M.D. at The University of Iowa reported programmed necrosis in human neutrophils (Greenlee-Wacker et al., J Immunol 2014). Work performed in collaboration with Michael Otto, Ph.D. (LHBP) investigated the interaction of S. aureus phenol-soluble modulins with human Neutrophils (Cheung et al., FASEB J, 2014). These are only a few selected examples of studies performed in my Section, and a complete list of publications is provided below.
| 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 |
Showing the most recent 10 out of 62 publications
