A role for copper in protozoan grazing – two billion years selecting for bacterial copper resistance

Abstract

The Great Oxidation Event resulted in integration of soft metals in a wide range of biochemical processes including, in our opinion, killing of bacteria by protozoa. Compared to pressure from anthropologic copper contamination, little is known on impacts of protozoan predation on maintenance of copper resistance determinants in bacteria. To evaluate the role of copper and other soft metals in predatory mechanisms of protozoa, we examined survival of bacteria mutated in different transition metal efflux or uptake systems in the social amoeba Dictyostelium discoideum. Our data demonstrated a strong correlation between the presence of copper/zinc efflux as well as iron/manganese uptake, and bacterial survival in amoebae. The growth of protozoa, in turn, was dependent on bacterial copper sensitivity. The phagocytosis of bacteria induced upregulation of Dictyostelium genes encoding the copper uptake transporter p80 and a triad of Cu(I)-translocating P -type ATPases. Accumulated Cu(I) in Dictyostelium was monitored using a copper biosensor bacterial strain. Altogether, our data demonstrate that Cu(I) is ultimately involved in protozoan predation of bacteria, supporting our hypothesis that protozoan grazing selected for the presence of copper resistance determinants for about two billion years.

Bacterial resistance to arsenic protects against protist killing

“…1). Our data suggests that D. discoideum could use arsenic to kill the bacterial prey in the phagosome, which is inline with the copper and zinc poisoning of bacterial and fungi prey in the phagosome of macrophages (German et al 2013) and D. discoideum (Hao et al 2016). Notably, Cu(I) and As(III) are far more toxic than Zn(II) and if available would be a more toxic mix.…”

“…Recent data show that at least some protists forage on bacteria using toxic metals such as copper and maybe zinc in their phagosomes (Hao et al 2016). Dictyostelium discoideum ( D. discoideum ) as an ‘early’ macrophage shares several unique functions with mammalian phagocytic cells (Metchnikoff 1887).…”

Metal homeostasis and resistance in bacteria

“…Additionally, an ortholog of the Cu(I) transporter ATP7A in D. discoideum localized to both the cytoplasmic membrane and vacuolar structures, which indicates a possible use in flooding the phagocytic vacuole with Cu(I) 171 . Zn(II) and Cu(II) containing vesicles have also been observed before fusion with the protozoal phagosome 138,172 . Thus, selection for survival in protozoa may have primed bacterial cells to survive engulfment by mammalian phagocytes.…”

Think zinc: Role of zinc poisoning in the intraphagosomal killing of bacteria by the amoeba Dictyostelium

“…S1C), a plausible sign of Cu accumulation. Interestingly, the expression of the Dictyostelium homolog of the phagosomal copper transporter ATP7A is upregulated upon feeding with bacteria, consistent with a possible role of Cu poisoning during phagocytosis (Hao et al, 2016).…”