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 fungus Candida albicans sequesters essential Mg ²⁺ ions from the bacterium Pseudomonas aeruginosa . In turn, the bacterium competes using a Mg ²⁺ transporter, MgtA. We show that Mg ²⁺ sequestration by fungi is a general mechanism of antagonism against gram-negative bacteria. But the resultant Mg ²⁺ 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.