INVESTIGADORES
CHECA Susana Karina
congresos y reuniones científicas
Título:
A balance between resistance and virulence in the evolution of Salmonella copper homeostasis
Autor/es:
TERÁN I; MENDOZA JI; GIRI GF; CHECA SK; SONCINI FC
Lugar:
Salta
Reunión:
Congreso; LV Annual SAIB meeting and XIV PABMB Congress; 2019
Institución organizadora:
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Resumen:
Salmonellosis is among the most common foodborne diseases, with millions of human infections occurring worldwide every year. The ability of Salmonella to persist and proliferate both in contaminated food and water and within host?s tissues reflects the versatility of its genetic repertoire that allows adaption to diverse and challenging environmental conditions. This also involves the participation of regulatory systems that perceive specific host?s signals and respond to them by modulating the expression of factors essential for virulence. In particular, it has been shown that this pathogen detects the surge of copper (Cu) inside the Salmonella-containing vacuole in infected cells. In consequence, mutants affected in Cu-resistance have reduced survival in macrophages. Most known bacterial cuproproteins localize to the envelope, which makes this compartment the main target for Cu homeostasis. While in most enteric species periplasmic Cu homeostasis is maintained by the CusR/CusS-controlled CusCFBA efflux system that removes surplus cellular Cu ions, we noticed that this sensory and efflux system coding cus locus was lost in the core genome of most Salmonella subspecies. On the other hand, both Salmonella species acquired cueP, which codes for a periplasmic Cu-chaperone. We observed that mutants with a deletion in cueP have increased Cu sensitivity in anaerobic conditions, and that CueP can partially restore Cu-resistance of a Δcus E. coli mutant strain in the absence of oxygen, suggesting that the Salmonella periplasmic chaperone can substitute the CusCFBA system in the maintenance of the envelope Cu homeostasis. Reintroduction of the ancestral cus locus in the Salmonella chromosome did not affect Cu-resistance in aerobic conditions while its resistance to the metal ion in anaerobic conditions was even higher than that of the wild-type strain. Although the reasons for the loss of the ancestral locus are not clear, we speculated that virulence could be involved. In fact, we observed that regardless the presence or absence of the cus locus, the ΔcueP strain shows a deficiency in intracellular replication in macrophages compared to the wild type strain. Our results demonstrate that CueP and CusCFBA exert redundant functions for metal resistance, but not for macrophage survival and therefore for the virulence of this pathogen.