Host macrocyclic acylcarnitines mediate symbiotic interactions between frogs and their skin microbiome

Andrés E Brunetti; Mariana L Lyra; Anelize Bauermeister; Boyke Bunk; Christian Boedeker; Mathias Müsken; Fausto Carnevale Neto; Jacqueline Nakau Mendonça; Andrés Mauricio Caraballo-Rodríguez; Weilan G P Melo; Mônica T Pupo; Célio F B Haddad; Gabriela M Cabrera; Jörg Overmann; Norberto P Lopes

doi:10.1016/j.isci.2023.108109

Host macrocyclic acylcarnitines mediate symbiotic interactions between frogs and their skin microbiome

iScience. 2023 Oct 4;26(11):108109. doi: 10.1016/j.isci.2023.108109. eCollection 2023 Nov 17.

Authors

Andrés E Brunetti^{1

2

3}, Mariana L Lyra⁴, Anelize Bauermeister⁵, Boyke Bunk⁶, Christian Boedeker⁶, Mathias Müsken⁷, Fausto Carnevale Neto⁸, Jacqueline Nakau Mendonça², Andrés Mauricio Caraballo-Rodríguez⁹, Weilan G P Melo¹⁰, Mônica T Pupo¹⁰, Célio F B Haddad¹¹, Gabriela M Cabrera^{12

13}, Jörg Overmann⁶, Norberto P Lopes²

Affiliations

¹ Instituto de Biología Subtropical (IBS, UNaM-CONICET), Posadas, Misiones N3300LQH, Argentina.
² NPPNS, Department of Biomolecular Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil.
³ Department of Insect Symbiosis, Max Planck Institute for Chemical Ecology, Hans-Knoell-Straße 8, 07745 Jena, Germany.
⁴ New York University Abu Dhabi, Saadiyat Island, Abu Dhabi 129188, United Arab Emirates.
⁵ Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo 05508-000, Brazil.
⁶ Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Niedersachsen, Germany.
⁷ Central Facility for Microscopy, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Niedersachsen, Germany.
⁸ Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
⁹ Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
¹⁰ Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil.
¹¹ Departamento de Biodiversidade e Centro de Aquicultura da UNESP (CAUNESP), Instituto de Biociências, UNESP-Universidade Estadual Paulista, Rio Claro, São Paulo 13506-900, Brazil.
¹² Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.
¹³ Unidad de Microanálisis y Métodos Físicos aplicados a la Química Orgánica (UMYMFOR), Buenos Aires C1428EGA, Argentina.

Abstract

The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts' health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs' skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs' skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs' multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

Keywords: Biological sciences; Metabolomics; Microbial metabolism; Microbiology; Omics.