Local Phenomena Shape Backyard Soil Metabolite Composition

Soil covers most of Earth’s continental surface and is fundamental to life-sustaining processes such as agriculture. Given its rich biodiversity, soil is also a major source for natural product drug discovery from soil microorganisms. However, the study of the soil small molecule profile has been challenging due to the complexity and heterogeneity of this matrix. In this study, we implemented high-resolution liquid chromatography–tandem mass spectrometry and large-scale data analysis tools such as molecular networking to characterize the relative contributions of city, state and regional processes on backyard soil metabolite composition, in 188 soil samples collected from 14 USA States, representing five USA climate regions. We observed that region, state and city of collection all influence the overall soil metabolite profile. However, many metabolites were only detected in unique sites, indicating that uniquely local phenomena also influence the backyard soil environment, with both human-derived and naturally-produced (plant-derived, microbially-derived) metabolites identified. Overall, these findings are helping to define the processes that shape the backyard soil metabolite composition, while also highlighting the need for expanded metabolomic studies of this complex environment.This research was supported by start-up funds from the University of Oklahoma (to L.-I.M.). Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease

Chagas disease (CD) is a parasitic disease caused by Trypanosoma cruzi protozoa, presenting with cardiomyopathy, megaesophagus, and/or megacolon. To determine the mechanisms of gastrointestinal (GI) CD tissue tropism, we systematically characterized the spatial localization of infection-induced metabolic and microbiome alterations, in a mouse model of CD. Notably, the impact of the transition between acute and persistent infection differed between tissue sites, with sustained large-scale effects of infection in the esophagus and large intestine, providing a potential mechanism for the tropism of CD within the GI tract. Infection affected acylcarnitine metabolism; carnitine supplementation prevented acute-stage CD mortality without affecting parasite burden by mitigating infection-induced metabolic disturbances and reducing cardiac strain. Overall, results identified a previously-unknown mechanism of disease tolerance in CD, with potential for new therapeutic regimen development. More broadly, results highlight the potential of spatially resolved metabolomics to provide insight into disease pathogenesis and infectious disease drug development.Open Access fees paid for in whole or in part by the University of Oklahoma Libraries. This work was supported by start-up funds from the University of Oklahoma to L.-I.M. and the National Institute of Allergy and Infectious Diseases of the NIH under award number R21AI148886 to L.-I.M. Initial tissue collection was supported by a postdoctoral fellowship to L.-I.M. from the Canadian Institutes of Health Research (award number 338511; www.cihr-irsc.gc.ca/). Microbial community analysis was supported, in part, by an NIH grant (award number NIH 2R01-GM089886 to K.S). Immunological characterization was performed on instrumentation from the OU Protein Production and Characterization Core facility, supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the NIH under grant number P20GM103640. Histology samples were processed by the University of Oklahoma Health Sciences Center, Stephenson Cancer Center Tissue Pathology Shared Resource, supported by the National Cancer Institute Cancer Center Support Grant P30CA225520 and COBRE P20GM103639. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.Ye

Metabolite Profiling Of Experimental Cutaneous Leishmaniasis Lesions Demonstrates Significant Perturbations In Tissue Glycerophosphocholines

Each year 700,000 to 1.2 million new cases of cutaneous leishmaniasis (CL) are reported and yet CL remains one of thirteen diseases classified as neglected tropical diseases (NTDs). Leishmania major is one of several different species of that same genus that can cause CL. Current CL treatments are limited by adverse effects and rising resistance. Studying disease metabolism at the site of infection can lead to new drug targets. In this study, samples were collected from mice infected in the ear and footpad with L. major and analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in overall metabolite profiles were noted in the ear at the site of the lesion. Interestingly, lesion-adjacent, macroscopically healthy sites also showed alterations in specific metabolites, including select phosphocholines (PCs). Host-derived PCs in the lower m/z range (m/z 200-799) showed an increase with infection in the ear at the lesion site, while those in the higher m/z range (m/z 800-899) were decreased with infection at the lesion site. Overall, our results expanded our understanding of the mechanisms of CL pathogenesis through the host metabolism and may lead to new curative measures against infection with Leishmania