Chemical Cartography Approaches to Study Trypanosomatid Infection

Dean, D. A.; Haffner, Jacob J.; Katemauswa, Mitchelle; McCall, Laura-Isobel

doi:10.3791/63255

Cited by 3 publications

(2 citation statements)

References 54 publications

(13 reference statements)

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“…The resulting supernatant was transferred to a new plate for LC-MS analysis. We have previously used this method to provide insight into the lipid and metabolic changes associated with different infectious diseases, including parasitic and viral infection (e.g., refs − ; video protocol in ref ), without leading to fewer lipid annotation classes, subclasses or ClassyFire chemical ontology direct parents (comparing ref where extracts were analyzed separately, vs ref where extracts were combined). Biological impact was observed on acylcarnitines and glycerophosphocholines in both cases. , …”

Section: Methodsmentioning

confidence: 99%

Metabolomic Analysis of Polymicrobial Wound Infections and an Associated Adhesive Bandage

Ness

Holmes

et al. 2023

J. Am. Soc. Mass Spectrom.

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Concerns about ion suppression, spectral contamination, or interference have led to avoidance of polymers in mass spectrometry (MS)-based metabolomics. This avoidance, however, has left many biochemical fields underexplored, including wounds, which are often treated with adhesive bandages. Here, we found that despite previous concerns, the addition of an adhesive bandage can still result in biologically informative MS data. Initially, a test LC-MS analysis was performed on a mixture of known chemical standards and a polymer bandage extract. Results demonstrated successful removal of many polymer-associated features through a data processing step. Furthermore, the bandage presence did not interfere with metabolite annotation. This method was then implemented in the context of murine surgical wound infections covered with an adhesive bandage and inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, or a 1:1 mix of these pathogens. Metabolites were extracted and analyzed by LC-MS. On the bandage side, we observed a greater impact of infection on the metabolome. Distance analysis showed significant differences between all conditions and demonstrated that coinfected samples were more similar to S. aureus-infected samples compared to P. aeruginosa-infected samples. We also found that coinfection was not merely a summative effect of each monoinfection. Overall, these results represent an expansion of LC-MS-based metabolomics to a novel, previously under-investigated class of samples, leading to actionable biological information.

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Section: Methodsmentioning

confidence: 99%

Metabolomic Analysis of Polymicrobial Wound Infections and an Associated Adhesive Bandage

Ness

Holmes

et al. 2023

J. Am. Soc. Mass Spectrom.

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“…Secondary metabolites are not directly involved in the metabolism of the biological system but rather can mediate activities that enhance its survival [4]. In addition to the primary and secondary metabolites, some compounds of drug and food origin are also small molecules that can affect host-pathogen interactions [5]. Here, we will use "metabolites" in the broadest sense encompassing all those molecules, including lipids (Fig 1) [6].…”

Section: Small Molecules Metabolites and Metabolomicsmentioning

confidence: 99%

Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease

Kwakye-Nuako,

Middleton,

McCall

2024

PLoS Pathog

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Small molecules (less than 1,500 Da) include major biological signals that mediate host-pathogen-microbiome communication. They also include key intermediates of metabolism and critical cellular building blocks. Pathogens present with unique nutritional needs that restrict pathogen colonization or promote tissue damage. In parallel, parts of host metabolism are responsive to immune signaling and regulated by immune cascades. These interactions can trigger both adaptive and maladaptive metabolic changes in the host, with microbiome-derived signals also contributing to disease progression. In turn, targeting pathogen metabolic needs or maladaptive host metabolic changes is an important strategy to develop new treatments for infectious diseases. Trypanosoma cruzi is a single-celled eukaryotic pathogen and the causative agent of Chagas disease, a neglected tropical disease associated with cardiac and intestinal dysfunction. Here, we discuss the role of small molecules during T. cruzi infection in its vector and in the mammalian host. We integrate these findings to build a theoretical interpretation of how maladaptive metabolic changes drive Chagas disease and extrapolate on how these findings can guide drug development.

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The intersection of host in vivo metabolism and immune responses to infection with kinetoplastid and apicomplexan parasites

Ewald,

Nasuhidehnavi,

Feng

et al. 2024

Microbiol Mol Biol Rev

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SUMMARY Protozoan parasite infection dramatically alters host metabolism, driven by immunological demand and parasite manipulation strategies. Immunometabolic checkpoints are often exploited by kinetoplastid and protozoan parasites to establish chronic infection, which can significantly impair host metabolic homeostasis. The recent growth of tools to analyze metabolism is expanding our understanding of these questions. Here, we review and contrast host metabolic alterations that occur in vivo during infection with Leishmania , trypanosomes, Toxoplasma , Plasmodium, and Cryptosporidium . Although genetically divergent, there are commonalities among these pathogens in terms of metabolic needs, induction of the type I immune responses required for clearance, and the potential for sustained host metabolic dysbiosis. Comparing these pathogens provides an opportunity to explore how transmission strategy, nutritional demand, and host cell and tissue tropism drive similarities and unique aspects in host response and infection outcome and to design new strategies to treat disease.

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Chemical Cartography Approaches to Study Trypanosomatid Infection

Cited by 3 publications

References 54 publications

Metabolomic Analysis of Polymicrobial Wound Infections and an Associated Adhesive Bandage

Metabolomic Analysis of Polymicrobial Wound Infections and an Associated Adhesive Bandage

Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease

The intersection of host in vivo metabolism and immune responses to infection with kinetoplastid and apicomplexan parasites

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