INVESTIGADORES
LÓPEZ MarÍa Carolina
congresos y reuniones científicas
Título:
COMPARATIVE ANALYSIS OF CUEP AND CUS FOR SALMONELLA PERIPLASMIC COPPER HOMEOSTASIS AND VIRULENCE
Autor/es:
LÓPEZ, CAROLINA; GIRI, GERMÁN F.; PEZZA, ALEJANDRO; PONTEL, LUCAS BLAS; SONCINI, FERNANDO C.
Lugar:
Potsdam
Reunión:
Conferencia; 5th ASM Conference on Salmonella; 2016
Institución organizadora:
American Society for Microbiology
Resumen:
Copper is an essential ion that participates in enzymatic reactions carried out by bacterial periplasmic cuproproteins such as cytochrome oxidases, NADH dehydrogenases, Cu, Zn superoxide dismutases, laccases and multicopper oxidases, among others. It is, at the same time, extremely reactive causing damage to proteins, lipids and other cellular components. Most enterobacterial species harbor a copper responsive two component system, CusR/CusS, to control the ion levels in the cell envelope. CusR/CusS responds to the surplus of periplasmic copper inducing the expression of the CBAtype efflux complex CusC(F)BA that pumps out of the cell the excess of the metal ion. Most Salmonella serotypes lack both the genes coding for CusR/CusS and the operon encoding the CusC(F)BA efflux complex, and different lines of evidence suggest that envelope protection against copper overload depends on CueP, a major copper binding protein in the periplasm required for macrophage survival and virulence. The Salmonella specific CueP coding gene was originally identified as part of the Cue regulon under the transcriptional control of the cytoplasmic copper sensor CueR, but itsexpression differs from the rest of CueR regulated genes. We now show that cueP expression is controlled by the concerted action of CueR, which detects the presence of copper in the cytoplasm, and by CpxR/CpxA that monitors envelope stress. The integration of two ancestral sensory systems CueR, which provides a signal specificity, and CpxR/CpxA that detects stress in the bacterial envelope restricts the expression of this periplasmic copper resistance protein only to cells encountering surplus copper that disturbs envelope homeostasis, emulating the role of the CusR/CusS regulatory system present in other enteric bacteria.Furthermore, we show that coordinated regulation of cueP by CueR and CpxR/CpxA is required for optimal growth. CueP . expression from a CpxR independent promoter impairs growth during exponential phase. In addition, this strain shows a marked growth defect in presence of H2O2. Finally, a strain with the Escherichia coli cus locus in place of cueP showed displayed wild type resistance to the metal ion but showed a deficiency was unable to survive in macrophage survival, suggesting that cueP acquisition by Salmonella was necessary to establish its intracellular lifestyle