Widespread fungal-bacterial competition for magnesium enhances antibiotic resistance

Fungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Using unbiased genomic approaches, we discover that the fungusCandida albicanssequesters essential Mg²⁺ions from the bacteriumPseudomonas aeruginosa. In turn, the bacterium competes using a Mg²⁺transporter, MgtA. We show that Mg²⁺sequestration by fungi is a general mechanism of antagonism against gram-negative bacteria. But the resultant Mg²⁺limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Experimental evolution reveals that bacteria in co-culture with fungi become phenotypically, but not genetically, resistant to colistin; antifungal treatment renders resistant bacteria from co-cultures to become colistin-sensitive. Fungal-bacterial nutritional competition may thus profoundly impact treatments of polymicrobial infections with antibiotics of last resort.