Browsing by Subject "Methicillin-resistant staphylococcus aureus"

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    1735. The Pig Skin Commensal D. incerta Exhibits Antimicrobial Activity Against Methicillin-Resistant Staphylococcus aureus
    (Oxford University Press, 2022) Wei, Monica; Knight, Simon; Flowers, Laurice; Walsh, Jasmine; Grice, Elizabeth A.; Medicine, School of Medicine
    Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections occur commonly on skin and cause significant healthcare burden. MRSA can also stably colonize the skin and nasal passages, contributing to community spread. This colonization results in long-term interaction with the skin microbiome, which harbors a diverse community of bacteria that often use antimicrobial molecules to compete for ecologic niches. We hypothesize that the skin microbiome contains bacteria that secrete novel antimicrobial agents against MRSA. Methods: Pigs are an established model organism for skin whose microbiome is not well explored. We mined the pig skin microbiome for bacterial species that inhibited MRSA via a modified disc diffusion assay. Results: We find that the novel pig skin commensal D. incerta inhibits USA300 strain MRSA via a secreted antimicrobial protein that can be isolated from cell-free supernatant. Analysis of the D. incerta genome shows little homology to known antimicrobial genes clusters. The identity of the antimicrobial molecule and whether its antimicrobial activity persists in the context of MRSA skin infection remain unclear. We characterize the identity of this antimicrobial molecule via parallel genomic and biochemical approaches. Finally, we propose to test the ability of D. incerta to impede MRSA colonization and improve healing of MRSA-mediated skin infection, two clinically important skin conditions. Conclusion: We screened the pig skin microbiome and successfully identified bacterial inhibitors of MRSA. Preliminary data suggest that the pig skin commensal D. incerta secretes a novel antimicrobial protein. Our current efforts focus on identifying this antimicrobial molecule and investigating its therapeutic potential in animal models of skin.
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    STAT4 is expressed in neutrophils and promotes antimicrobial immunity
    (American Society for Clinical Investigation, 2021-07-22) Mehrpouya-Bahrami, Pegah; Moriarty, Alina K.; De Melo, Paulo; Keeter, W. Coles; Alakhras, Nada S.; Nelson, Andrew S.; Hoover, Madeline; Barrios, Maria S.; Nadler, Jerry L.; Serezani, C. Henrique; Kaplan, Mark H.; Galkina, Elena V.; Microbiology and Immunology, School of Medicine
    Signal transducer and activator of transcription 4 (STAT4) is expressed in hematopoietic cells and plays a key role in the differentiation of T helper 1 cells. Although STAT4 is required for immunity to intracellular pathogens, the T cell-independent protective mechanisms of STAT4 are not clearly defined. In this report, we demonstrate that STAT4-deficient mice were acutely sensitive to methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that STAT4 was expressed in neutrophils and activated by IL-12 via a JAK2-dependent pathway. We demonstrate that STAT4 was required for multiple neutrophil functions, including IL-12-induced ROS production, chemotaxis, and production of the neutrophil extracellular traps. Importantly, myeloid-specific and neutrophil-specific deletion of STAT4 resulted in enhanced susceptibility to MRSA, demonstrating the key role of STAT4 in the in vivo function of these cells. Thus, these studies identify STAT4 as an essential regulator of neutrophil functions and a component of innate immune responses in vivo.