<i>Staphylococcus aureus</i>promotes increase IL-1 mediated immunopathology and delayed healing in cutaneous leishmaniasis

Abstract The chronic infection by Leishmania braziliensis causes a skin barrier (ulcer) breach and is susceptible to secondary bacterial infections. development of the ulcer associated with dysregulation microbiome, which we hypothesized impacts host gene expression, exacerbates inflammatory response, prolongs resolution disease. We conducted an integrative multi-omics meta-analysis clinical metadata patients. found that high burden was increased response delayed healing. 16S-seq analysis lesion swabs revealed while patients exhibit several distinct microbiomes, microbiome dominated Staphylococcus most common. Furthermore, dominant lesional were in healing compared those heterogeneous microbiome. Since S. aureus common isolate from ulcers, carried out dual RNA-seq on biopsies quantify transcriptional abundances them expression. High transcript abundance expression IL-1α IL-1β. These cytokines critical for modulating disease outcome since pathology reduced when neutralized either L. braziliensis-infected mice colonized aureus. results indicate altered develops cutaneous leishmaniasis, influencing responsiveness anti-parasitic drug treatment. They suggest host-directed therapies designed reduce leishmanial lesions may be therapeutic. NIH (AI143790)