Survival in amoeba: a major selection pressure on the presence of bacterial copper and zinc resistance determinants?: identification of a "copper pathogenicity island"

The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the "copper pathogenicity island" identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs

Copper Stress Targets the Rcs System To Induce Multiaggregative Behavior in a Copper-Sensitive Salmonella Strain▿

Salmonella ΔcuiD strains form mucoid colonies on copper-containing solid media. We show here that this multiaggregative behavior is caused by the Rcs-dependent induction of colanic acid extracellular polysaccharide. Deletion of cps operon genes in a ΔcuiD strain increased the sensitivity to copper, indicating a role for colanic acid in copper resistance

Evolution of Copper Homeostasis and Virulence in Salmonella

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.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.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.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.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.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.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

The protein scaffold calibrates metal specificity and activation in MerR sensors

Abstract MerR metalloregulators are the central components of many biosensor platforms designed to report metal contamination. However, most MerR proteins are non‐specific. This makes it difficult to apply these biosensors in the analysis of real environmental samples. On‐demand implementation of molecular engineering to modify the MerR metal preferences is innovative, although it does not always yield the expected results. As the metal binding loop region (MBL) of these sensors has been proposed to be the major modulator of their specificity, we surgically switched this region for that of well‐characterized specific and non‐specific homologues. We found that identical modifications in different MerR proteins result in synthetic sensors displaying particular metal‐detection patterns that cannot be predicted from the nature of the assembled modules. For instance, the MBL from a native Hg(II) sensor provided non‐specificity or specificity toward Hg(II) or Cd(II) depending on the MerR scaffold into which it was integrated. These and other evidences reveal that residues outside the MBL are required to modulate ion recognition and transduce the input signal to the target promoter. Revealing their identity and their interactions with other residues is a critical step toward the design of more efficient biosensor devices for environmental metal monitoring