Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes
The innate immune responses of mammals to microbial infections include strategies based on manipulating the local concentration of metals such as iron (Fe) and zinc (Zn), commonly described as nutritional immunity. To evaluate whether these strategies are also present in zebrafish embryos, we have c...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/944 |
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| author | Valerio Secli Claudia Di Biagio Arianna Martini Emma Michetti Francesca Pacello Serena Ammendola Andrea Battistoni |
| author_facet | Valerio Secli Claudia Di Biagio Arianna Martini Emma Michetti Francesca Pacello Serena Ammendola Andrea Battistoni |
| author_sort | Valerio Secli |
| collection | DOAJ |
| description | The innate immune responses of mammals to microbial infections include strategies based on manipulating the local concentration of metals such as iron (Fe) and zinc (Zn), commonly described as nutritional immunity. To evaluate whether these strategies are also present in zebrafish embryos, we have conducted a series of heart cavity-localized infection experiments with <i>Pseudomonas aeruginosa</i> strains characterized by a different ability to acquire Zn. We have found that, 48 h after infection, the bacterial strains lacking critical components of the Zn importers ZnuABC and ZrmABCD have a reduced colonization capacity compared to the wild-type strain. This observation, together with the finding of a high level of expression of Zur-regulated genes, suggests the existence of antimicrobial mechanisms based on Zn sequestration. However, we have observed that strains lacking such Zn importers have a selective advantage over the wild-type strain in the early stages of infection. Analysis of the expression of the gene that encodes for a Zn efflux pump has revealed that at short times after infection, <i>P. aeruginosa</i> is exposed to high concentrations of Zn. At the same time, zebrafish respond to the infection by activating the expression of the Zn transporters Slc30a1 and Slc30a4, whose mammalian homologs mediate a redistribution of Zn in phagocytes aimed at intoxicating bacteria with a metal excess. These observations indicate that teleosts share similar nutritional immunity mechanisms with higher vertebrates, and confirm the usefulness of the zebrafish model for studying host–pathogen interactions. |
| first_indexed | 2024-03-09T12:27:59Z |
| format | Article |
| id | doaj.art-a84a50e12acf47feba988f5f25d7742d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:27:59Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a84a50e12acf47feba988f5f25d7742d2023-11-30T22:32:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124294410.3390/ijms24020944Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher EukaryotesValerio Secli0Claudia Di Biagio1Arianna Martini2Emma Michetti3Francesca Pacello4Serena Ammendola5Andrea Battistoni6Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, ItalyLaboratory of Experimental Ecology and Aquaculture, Department of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyLaboratory of Experimental Ecology and Aquaculture, Department of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, ItalyThe innate immune responses of mammals to microbial infections include strategies based on manipulating the local concentration of metals such as iron (Fe) and zinc (Zn), commonly described as nutritional immunity. To evaluate whether these strategies are also present in zebrafish embryos, we have conducted a series of heart cavity-localized infection experiments with <i>Pseudomonas aeruginosa</i> strains characterized by a different ability to acquire Zn. We have found that, 48 h after infection, the bacterial strains lacking critical components of the Zn importers ZnuABC and ZrmABCD have a reduced colonization capacity compared to the wild-type strain. This observation, together with the finding of a high level of expression of Zur-regulated genes, suggests the existence of antimicrobial mechanisms based on Zn sequestration. However, we have observed that strains lacking such Zn importers have a selective advantage over the wild-type strain in the early stages of infection. Analysis of the expression of the gene that encodes for a Zn efflux pump has revealed that at short times after infection, <i>P. aeruginosa</i> is exposed to high concentrations of Zn. At the same time, zebrafish respond to the infection by activating the expression of the Zn transporters Slc30a1 and Slc30a4, whose mammalian homologs mediate a redistribution of Zn in phagocytes aimed at intoxicating bacteria with a metal excess. These observations indicate that teleosts share similar nutritional immunity mechanisms with higher vertebrates, and confirm the usefulness of the zebrafish model for studying host–pathogen interactions.https://www.mdpi.com/1422-0067/24/2/944nutritional immunityzinc transportzebrafish<i>P. aeruginosa</i>host–pathogen interaction |
| spellingShingle | Valerio Secli Claudia Di Biagio Arianna Martini Emma Michetti Francesca Pacello Serena Ammendola Andrea Battistoni Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes International Journal of Molecular Sciences nutritional immunity zinc transport zebrafish <i>P. aeruginosa</i> host–pathogen interaction |
| title | Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes |
| title_full | Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes |
| title_fullStr | Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes |
| title_full_unstemmed | Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes |
| title_short | Localized Infections with <i>P. aeruginosa</i> Strains Defective in Zinc Uptake Reveal That Zebrafish Embryos Recapitulate Nutritional Immunity Responses of Higher Eukaryotes |
| title_sort | localized infections with i p aeruginosa i strains defective in zinc uptake reveal that zebrafish embryos recapitulate nutritional immunity responses of higher eukaryotes |
| topic | nutritional immunity zinc transport zebrafish <i>P. aeruginosa</i> host–pathogen interaction |
| url | https://www.mdpi.com/1422-0067/24/2/944 |
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