Global copper response of the soil bacterial predator Myxococcus xanthus and its contribution to antibiotic cross-resistance

Copper accumulation in agricultural soils poses environmental challenges by selecting copper-resistant bacteria and also contributing to the co-selection of antibiotic-resistant bacteria. In addition, copper influences bacterial predator-prey interactions, potentially altering microbial ecosystems. Myxococcus xanthus , a soil-dwelling bacterium, preys on other microorganisms, including Sinorhizobium meliloti , a symbiotic nitrogen-fixing bacterium associated with leguminous plants. The role of copper in M. xanthus interactions remains poorly understood, although it accumulates at the predator-prey interface. In this study, we explore the transcriptomic response of M. xanthus to copper stress in both monocultures and co-cultures with S. meliloti . Our analysis identified many myxobacterial copper-regulated transcripts, and studies on mutant strains in some copper-induced genes revealed the role of two efflux pumps in cross-resistance to copper and tetracyclines. These findings provide new insights into the adaptive mechanisms of M. xanthus in response to copper, with implications for the co-selection of antibiotic resistance and the broader impact of copper on microbial community dynamics in soil ecosystems. ● Copper detoxification is similar both in monocultures and during predation. ● Transcriptional changes suggest a putative new system for copper acquisition. ● Copper triggers a lower oxidative stress response in M. xanthus during predation. ● Two copper-inducible pumps offer cross-resistance to tetracyclines and kanamycin.