Spontaneous mutation in the AgrRS two-component regulatory system ofCupriavidus metalliduransresults in enhanced silver resistance

Abstract

Cupriavidus metallidurans is able to adapt to toxic silver concentrations and previously uncharacterized periplasmic proteins played a crucial role in this adaptation process.

DNA-Binding and Transcription Activation by Unphosphorylated Response Regulator AgrR From Cupriavidus metallidurans Involved in Silver Resistance

“…In contrast with the microarray approach, two of the seven genes (v2_1370 and prsQ 1 ) were not differentially expressed based on RNA-seq. The latter corroborates with previous data from a plasmid-based promoter probe reporter that showed no differential expression in NA4S compared with NA4 (Mijnendonckx et al, 2019). The NA4 systems homologous to known silver detoxification systems (silDCBA and cusDCBAF operons coding for HME-RND-driven efflux systems, and cupRAC coding for a P IB1 -type ATPase) were not differentially expressed in NA4S ( Table 1).…”

“…From the general overview plot ( Supplementary Figure 1), it is noticeable that apparently many genes on the pNA4_A, pNA4_B and pNA4_C plasmids are upregulated. Specifically related to the previously identified targets (Mijnendonckx et al, 2019), prsQ 2 is with a 507-fold increase the most highly upregulated gene in NA4S. The agrRS genes (with agrS mutated) are also highly upregulated ( Table 1).…”

“…AgrS is part of the two-component regulatory system AgrRS, which was previously uncharacterized and not associated with any phenotype in C. metallidurans or other bacteria. AgrS inactivation resulted in enhanced expression of a small set of genes, including agrR, suggesting a crucial role for this RR in the enhanced resistance (Mijnendonckx et al, 2019). The importance of AgrR and of PrsQ 1 and PrsQ 2 , two predicted small periplasmic proteins, in the observed metal-resistant phenotype was further confirmed by the loss of resistance in cognate deletion derivatives of the silver resistant mutant NA4S (Mijnendonckx et al, 2019).…”

“…Recently, we have isolated several laboratory-adapted C. metallidurans mutants derived from different strains (CH34, AE104, NA4) that are capable of growing at much higher silver concentrations than the cognate parental strains (Mijnendonckx et al, 2019). Remarkably, none of the well-known silver resistance mechanisms, including the RND efflux pumps encoded by the silDCBA and cusDCBAF operons, and the P-type ATPase efflux pump encoded by the cupRAC operon (Monchy et al, 2007;Bersch et al, 2011;Monsieurs et al, 2011;Mergeay and Van Houdt, 2015), are involved in the adapted response.…”

<p>Silver Nanoparticles for the Therapy of Tuberculosis</p>

“…[255][256][257][258] The widespread use of Agand Ag-ions containing nanomaterials and nanocomposites is considered to be the main determinant in a possible bacterial selection and evolution towards a biological resistance to Ag NP and/of Ag ions. 258,259 The resistance to antibacterial Ag is reported among nosocomial infections, 260 in bacteria present within wounds, including burns, [261][262][263][264] diabetic foot ulcers, 265 dental bacteria, 266,267 or exterior natural-environments containing high amounts of Ag. 268 Occasionally, the resistance towards Ag is developed in parallel with the multidrug-resistance, as shown in Staphylococcus aureus, klebsiella pneumoniae, Acinetobacter baumannii, and Enterococcus faecium.…”