Evolution of Copper Homeostasis and Virulence in Salmonella

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dc.creator Méndez, Andrea A. E.
dc.creator Mendoza, Julián I.
dc.creator Echarren, María Laura
dc.creator Terán, Ignacio
dc.creator Checa, Susana Karina
dc.creator Soncini, Fernando C.
dc.date.accessioned 2022-05-20T15:28:08Z
dc.date.available 2022-05-20T15:28:08Z
dc.date.issued 2022-03-16
dc.identifier.issn 1664-302X
dc.identifier.uri http://hdl.handle.net/2133/23694
dc.description Salmonella enterica sv. Typhimurium modulates the expression of factors essential for virulence, contributing to its survival against the surge of copper (Cu) in the Salmonella-containing vacuole. This bactericidal host innate immune component primarily targets the bacterial envelope, where most cuproproteins are localized. While in most enteric species periplasmic Cu homeostasis is maintained by the CusR/CusS-controlled CusCFBA efflux system encoded in the cus locus, we noticed that these genes were lost from the Salmonella-core genome. At the same time, Salmonella acquired cueP, coding for a periplasmic Cu chaperone. As cus, cueP was shown to be essential for bacterial survival in a copper-rich environment under anaerobiosis, suggesting that it can functionally substitute the CusCFBA system. In the present study, the whole Escherichia coli cus locus was reintroduced to the chromosome of the Salmonella wild-type or th 1cueP strain. While the integrated cus locus did not affect Cu resistance under aerobic conditions, it increases Cu tolerance under anaerobiosis, irrespective of the presence or absence of cueP. In contrast to the Cus system, CueP expression is higher at high copper concentrations and persisted over time, suggesting separate functions. Finally, we observed that, regardless of the presence or absence of cus, a mutant deleted of cueP shows a deficiency in replication inside macrophages compared to the wild- type strain. Our results demonstrate that CueP and CusCFBA exert redundant functions for metal resistance, but not for intracellular survival, and therefore for the virulence of this pathogen. es
dc.description.sponsorship Agencia Nacional de Promoción Científica y Tecnológica: PICT-2018-02122
dc.description.sponsorship National Institutes of Health: R01GM114949
dc.format application/pdf
dc.format.extent 1-11
dc.language.iso eng es
dc.publisher Frontiers Media es
dc.rights openAccess es
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ *
dc.subject Copper es
dc.subject Bacterial envelope es
dc.subject CueP es
dc.subject CusCFBA es
dc.subject Host-pathogen interaction es
dc.title Evolution of Copper Homeostasis and Virulence in Salmonella es
dc.rights.holder Méndez, Andrea A. E. es
dc.rights.holder Mendoza, Julián I. es
dc.rights.holder Echarren, María Laura es
dc.rights.holder Terán, Ignacio es
dc.rights.holder Checa, Susana Karina es
dc.rights.holder Soncini, Fernando C. es
dc.relation.publisherversion https://doi.org/10.3389/fmicb.2022.823176
dc.relation.publisherversion https://www.frontiersin.org/articles/10.3389/fmicb.2022.823176/full
dc.rights.text Attribution 4.0 International (CC BY 4.0) es
dc.description.fil Fil: Méndez, Andrea A. E. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Mendoza, Julián I. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Echarren, María Laura. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Terán, Ignacio. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Checa, Susana Karina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Soncini, Fernando C. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.


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