Table 2.

Zinc detoxification strategies of intracellular pathogens and their association with survival and virulence.

Pathogen	Locus/Gene	Function	Infection model	Phenotype	Reference
Transportation
M. tuberculosis	ctpC	Inner membrane P1B-type ATPase, efflux	Human monocyte-derived macrophages	Decreased survival of mutant	[22]
*E. coli	zntA	Inner membrane P1B-type ATPase, efflux	Human monocyte-derived macrophages	Decreased survival of mutant	[22]
			Neutrophils	Decreased survival of mutant	[51]
Group A Streptococcus	czcD	CDF family transporter; efflux	Neutrophils	Decreased survival of mutant	[52,53]
			Invasive subcutaneous; humanized plasminogen transgenic mouse	Decreased initial lesion size, dissemination in blood, mortality of mice Decreased survival relative to wild-type in competitive infection	[52,53]
S. Typhimurium	Salmonella pathogenicity island-1	Delivery of bacterial effector molecules; unknown mechanism	Human monocyte-derived macrophages	Prevents co-localization of phagosomes with Zn-containing vesicles	[51]
	zntA and zitB	Inner membrane P1B-type ATPase and CDF family transporters, respectively; efflux	Competitive intraperitoneal challenge; mouse	Reduced recovery of ΔzntA ΔzitB mutant from liver and spleen	[58]
Regulation
S. pneumoniae	sczA	Transcriptional activator of Zn efflux; regulation of Zn homeostasis	Human monocyte-derived macrophages	Decreased survival of mutant	[61]
Group A Streptococcus	gczA (sczA)	Transcriptional activator of Zn efflux; regulation of Zn homeostasis	Neutrophils	Decreased survival of mutant	[52]
			Invasive subcutaneous; humanized plasminogen transgenic mouse	Decreased mortality of mice	[52]

^*Non-pathogenic, but providec as a model Gram-negative organism.