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Illustration of silver to re-sensitise colistin against pathogen carrying mcr gene in vitro and in vivo. Cartoon of active-site pocket of MCR-1-S enzyme with cofactor Zn2+ shown as the blue sphere (upper left) and the novel tetra-nuclear silver center in the active-site pocket of Ag-MCR-1-S (upper right). Ag+ shown as wheat spheres are bridged in a narrow pocket by either coordination bonds (red solid lines) or hydrogen bond (red dash line).The substitution of Zn2+ from MCR-1-S by Ag+ and inhibition of substrate (phosphorylethanolamine, pEtN) bound to MCR-1-S enzyme result in the loss of enzyme activity, which is reflected by the recovered membrane potential (middle right). Growth curves of MCR-1-J53, a pathogen carrying mcr-1 gene, treated with different drugs in vitro (lower right) and bacterial load in abscess area on day 7 in the skin of Balb/c mice infected with mcr-1 positive K. pneumoniae 9607 and received single dose of vehicle, mono-therapy of colistin, AgNO3, or their combination (i.e. AgNO3+colistin) (middle left). Resistance acquisition curves of MCR-1-J53 during 16 passages with the sub-inhibitory concentrations of colistin alone or combination of colistin and AgNO3 (lower left). The inset shows the normalized expression level of MCR-1 in MCR-1-J53 receiving different treatments.
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The University of Hong Kong
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