Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence

Abstract

For all microorganisms, acquisition of metal ions is essential for survival in the environment or in their infected host. Metal ions are required in many biological processes as components of metalloproteins and serve as cofactors or structural elements for enzymes. However, it is critical for bacteria to ensure that metal uptake and availability is in accordance with physiological needs, as an imbalance in bacterial metal homeostasis is deleterious. Indeed, host defense strategies against infection either consist of metal starvation by sequestration or toxicity by the highly concentrated release of metals. To overcome these host strategies, bacteria employ a variety of metal uptake and export systems and finely regulate metal homeostasis by numerous transcriptional regulators, allowing them to adapt to changing environmental conditions. As a consequence, iron, zinc, manganese, and copper uptake systems significantly contribute to the virulence of many pathogenic bacteria. However, during the course of our experiments on the role of iron and manganese transporters in extraintestinal Escherichia coli (ExPEC) virulence, we observed that depending on the strain tested, the importance of tested systems in virulence may be different. This could be due to the different set of systems present in these strains, but literature also suggests that as each pathogen must adapt to the particular microenvironment of its site of infection, the role of each acquisition system in virulence can differ from a particular strain to another. In this review, we present the systems involved in metal transport by Enterobacteria and the main regulators responsible for their controlled expression. We also discuss the relative role of these systems depending on the pathogen and the tissues they infect.

Siderophore vaccine conjugates protect against uropathogenicEscherichia coliurinary tract infection

“…3D). Notably, highly evolved iron acquisition strategies, including Aer and Ybt, are critical virulence factors for ExPEC and other pathogenic species within the Enterobacteriaceae (61,62). Therefore, by defining the protective efficacy of two stealth siderophores prevalent among pathogenic E. coli (39), we have determined that Ybt and Aer are valuable antigens that have not heretofore been included in any UTI vaccines and, more generally, exemplify the untapped resource of bacteria-specific small molecules as potential vaccine antigens.…”

Transcriptome Response to Heavy Metals in Sinorhizobium meliloti CCNWSX0020 Reveals New Metal Resistance Determinants That Also Promote Bioremediation by Medicago lupulina in Metal-Contaminated Soil

“…To study the Cu and Zn resistance mechanisms of S. meliloti CCNWSX0020, we carried out a preliminary experiment to find a sublethal dose that did not cause mortality due to metal exposure by measuring the growth curves of S. meliloti CCNWSX0020 in the presence of different CuSO 4 and ZnSO 4 concentrations (for CuSO 4 , 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM; and for ZnSO 4 , 0, 0.2, 0.4, 0.6, 0.8, and 1.0 mM) (see Fig. S1 in the supplemental material).…”

“…S1 in the supplemental material). Thereafter, S. meliloti CCNWSX0020 strains were exposed to 0.6 mM CuSO 4 or 0.2 mM ZnSO 4 and then analyzed in comparison with untreated (control) strains by nextgeneration sequencing using an Illumina HiSeq 4000 system. Moreover, to investigate the different responses of S. meliloti CCNWSX0020 to short-term and long-term metal stresses, we set two metal treatment time points.…”

“…Moreover, to investigate the different responses of S. meliloti CCNWSX0020 to short-term and long-term metal stresses, we set two metal treatment time points. One condition of interest was long-term exposure, where the cells were incubated for 24 h, to mid-exponential phase, in the presence of 0.6 mmol/liter CuSO 4 or 0.2 mmol/liter ZnSO 4 . In contrast, the other condition of interest was short-term exposure, where preincubated cells from midexponential phase were exposed to 0.6 mmol/liter CuSO 4 or 0.2 mmol/liter ZnSO 4 for 30 min.…”

“…To further explore the roles of the mutated genes, the maximum tolerable concentrations (MTCs) of various metal ions [AgNO 3 , CuSO 4 , ZnSO 4 , CdSO 4 , Pb(NO 3 ) 2 , NiSO 4 , and CoCl 2 ] in the S. meliloti CCNWSX0020 wild-type strain and seven mutants (Δomp, ΔcueO, ΔcopG, ΔcusA-like, ΔfixH-like, ΔHP, and ΔyedYZ) were determined on solid tryptone-yeast extract (TY) medium. For the S. meliloti CCNWSX0020 wild-type strain, the MTCs of the various tested metals were 1.6, 1.2, 0.26, and 3.4 mM for CuSO 4 , ZnSO 4 , CdSO 4 , and Pb(NO 3 ) 2 , respectively (Fig.…”