Figure 4.

a | Mn²⁺ and Zn²⁺ uptake systems in pathogenic Gram-negative bacteria. b | Mn²⁺ and Zn²⁺ uptake systems in pathogenic Gram-positive bacteria. c | Proposed mechanisms of Zn²⁺ detoxification by Gram-negative pathogens. On infection, Zn²⁺ accumulates in the phagolysosome, where it is toxic to bacteria. Gram-negative bacteria alleviate this Zn²⁺ toxicity primarily through efflux of excess Zn²⁺ from the cytoplasm. d | Proposed mechanisms of Zn²⁺ and Mn²⁺ detoxification by Gram-positive pathogens. Zn²⁺ can be exported from the bacterial cytoplasm by dedicated transporters. Mn²⁺ is usually imported by the ABC family pneumococcal surface adhesin (Psa) system, but when the extracellular Zn²⁺/Mn²⁺ ratio is high, Zn²⁺ binds PsaA, the substrate-binding protein of this Mn²⁺-specific transporter, preventing Mn²⁺ binding and uptake. CDF, cation diffusion facilitator; CM, cytoplasmic membrane; IM, inner membrane; MntH, Mn transport H; OM, outer membrane; Znu, Zn uptake protein.