Abstract Embargoed

Abstract Embargoed

David J. Sanabria-Rios

Department of Natural Sciences, Inter American University of Puerto Rico, Metropolitan Campus, San Juan, PR

Introduction/Background. Fatty acids (FA) are known to have antibacterial properties and represent a promising alternative for developing next-generation antibacterial agents to combat infectious diseases. FA plays an important role in how living organisms defend themselves from several diseases, including those caused by multi-drug-resistant bacteria.

Hypothesis/Goal of Study. The tremendous potential of FA to increase the bactericidal effects of other antibacterial drugs is an important property infrequently seen in other naturally-occurring compounds. Thus, more studies on FA antibacterial activity, conventional & alternative mechanisms, and biomedical applications are needed. This study aims to provide valuable knowledge about the most recent FA's antibacterial properties and how their chemical structure affects this activity. Additionally, this study aims to comprehend the conventional and novel processes behind these recently discovered FA antibacterial properties.

Methods and Results. Methods focusing on FA antibacterial activity, elucidating conventional & alternative mechanisms, and biomedical applications will be discussed. These methods include but are not limited to 1) broth dilution susceptibility tests; 2) organic synthetic strategies for preparing synthetic FA; 3) spectrophotometric approaches; 4) scanning electron microscopy; and 5) fluorescence microscopy.

Discussion/Conclusions. Information from this study will help us understand mechanistic aspects that explain the antibacterial activity of FA and apply this knowledge to develop the next-generation of FA with even greater efficacy as antibacterial agents.

Citation/Acknowledgements. We thank the Puerto Rico IDeA Network of Biomedical Research Excellence (PR-INBRE, Grant No. 5P20GM103475-20) for supporting this research work.

Hayden Roys, Anne Bowlin, Lucy Fry, Gopinath Venugopal, Manjunath Bettadapura, and Tiffany Weinkopff
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR

Introduction/Background. Vascular remodeling is a phenomenon seen in lesions following inoculation with Leishmania parasites. Within cutaneous lesions, Leishmania infection results in the infiltration of myeloid cells, such as inflammatory monocytes and macrophages, and is associated with hypoxic conditions, and lymphangiogenesis, or the formation of new lymphatic vessels. This low-oxygen environment is concomitant
with the expression of hypoxic inducible factors (HIFs), which induce vascular endothelial growth factor-A (VEGF-A) expression in macrophages during the infection. We find that dermal macrophages experience hypoxia,
and the HIF target Vegfa is preferentially expressed at the site of infection. 

Hypothesis/Goal of Study. Given that HIF mediates VEGF-A, and that VEGF-A/VEGFR-2 signaling stimulates lymphangiogenesis, the goal of this study is to define the relationship between myeloid HIF activation and lymphangiogenesis during L. major infection. 

Methods and Results. We show myeloid aryl hydrocarbon receptor nuclear translocator (ARNT)/HIF/VEGF-A signaling promotes dermal lymphangiogenesis. Concomitant with impaired lymphangiogenesis, deletion of myeloid ARNT/HIF signaling leads to an exacerbated inflammatory response associated with larger lesions and an increase in inflammatory monocytes at the site of infection, but no difference in parasite burdens. 

Discussion/Conclusions. Taken together, these data suggest lymphangiogenesis is critical in restricting immunopathology to allow lesion resolution to occur during cutaneous leishmaniasis.

Citation/Acknowledgements. This work was supported by the Center for Microbial Pathogenesis and Host Inflammatory Responses (funded by National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) Centers of Biomedical Research Excellence Grant P20-GM103625), the Arkansas IDeA Network for Biomedical Research Excellence (INBRE) (NIH NIGMS Centers of Biomedical Research Excellence Grant P20-GM103429), and the Oak Ridge Associated Universities (ORAU) 2019 Ralph E. Powe Junior Faculty Enhancement Award. This publication was also supported in part by funds provided by the National Center For Advancing Translational Sciences of the NIH under awards TL1 TR003109 and UL1 TR003107 for the Systems Pharmacology and Therapeutics (SPaT) NIH T32 training grant GM106999 to Lucy Fry.