The Brass Dagger: How macrophages deploy Zinc and Copper as an antibacterial weapon? - Archive ouverte HAL
Communication Dans Un Congrès Année : 2024

The Brass Dagger: How macrophages deploy Zinc and Copper as an antibacterial weapon?

Ronan Kapetanovic
Claudia Stocks
Kaustav das Gupta
Jessica von Pein
Matthew J Sweet

Résumé

Macrophages are part of our front-line immune response against bacterial infection. Modulation of the metal ions concentration is an extremely efficient weapon in the arsenal of these cells. Upon infection, they can restrict the access to metal ions such as Fe and Mg to limit the growth of the micro-organism, but can also accumulate Cu and Zn into vesicles to poison intracellular bacteria[1,2]. Bacterial infection or stimulation with lipopolysaccharide promote the formation of Zn and Cu vesicles of that merge with the bacteria-containing phagosome. Microscopy has revealed that both types of vesicles exist individually or are merged together. Finally, we found that supplementation in Zn and Cu synergise and increase the antibacterial response of macrophages[3]. Recently we have characterised how this flux of metal ions is regulated within the macrophage. Indeed, Zn transporter SLC30A1 is involved in the formation of zinc vesicle and the transport of Zn on the bacteria-containing vacuole[4]. We also discovered that the transporter CFTR - linked to cystic fibrosis - is critical for initiating the Zn toxicity in macrophages. Mutation or inhibition of this transporter blocks the formation of Zn vesicles and the flow of Zn onto the bacteria and, thus, increase intracellular bacterial survival[5]. Using innovative tools - such as probes, bacterial fluorescent reporter, or dual host/pathogen single cell RNAseq - we have explored the mechanisms of metal ions toxicity and how pathogenic bacteria, like pathogenic E. coli and Salmonella, subvert this antimicrobial pathway References [1] J.B. von Pein, C.J. Stocks, M.A. Schembri, R. Kapetanovic, M.J. Sweet. Cell Microbiol 23 (2021) e13268. [2] C.J. Stocks, M.A. Schembri, M.J. Sweet, R. Kapetanovic. J Leukoc Biol 103 (2018) 35–51. [3] R. Kapetanovic, N.J. Bokil, M.E. Achard, C.L. Ong, K.M. Peters, C.J. Stocks, M.D. Phan, M. Monteleone, K. Schroder, K.M. Irvine, B.M. Saunders, M.J. Walker, K.J. Stacey, A.G. McEwan, M.A. Schembri, M.J. Sweet. FASEB J 30 (2016) 1901–12. [4] C.J. Stocks, J.B. von Pein, J.E.B. Curson, J. Rae, M.D. Phan, D. Foo, N.J. Bokil, T. Kambe, K.M. Peters, R.G. Parton, M.A. Schembri, R. Kapetanovic, M.J. Sweet. J Leukoc Biol (2020). [5] K. Das Gupta, J.E.B. Curson, A.A. Tarique, R. Kapetanovic, M.A. Schembri, E. Fantino, P.D. Sly, M.J. Sweet. Proc. Natl. Acad. Sci. U.S.A. 121 (2024) e2315190121.
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hal-04610564 , version 1 (13-06-2024)

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  • HAL Id : hal-04610564 , version 1

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Ronan Kapetanovic, Claudia Stocks, Kaustav das Gupta, Jessica von Pein, Matthew J Sweet. The Brass Dagger: How macrophages deploy Zinc and Copper as an antibacterial weapon?. FrenchBic annual meeting / French-Japanese Symposium on BioInorganic chemistry, FrenchBic, Apr 2024, Marseille, France. ⟨hal-04610564⟩
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