Nanoantibiotic copper-cefazolin combats MRSA infection through a reverse Trojan horse strategy

The above results collectively indicate that the influx of Cu-CZO into the bacterial interior mediates the upregulation of CsoR in MRSA, which in turn leads to the downregulation of ctpV expression and that the amount of CopA alone has difficulty maintaining Cu2+ homeostasis within the bacterium, with increased intracellular Cu2+ and disorganization of copper metabolism; furthermore, the duration of action of CZO within the bacteria is prolonged, and the dual action of copper toxicity and CZO kills the bacteria. This key mechanism can be further investigated by conducting CopA functional validation in conjunction with the evaluation of the nanoantibiotic efflux capacity.