PfeT, a P1B4 -type ATPase, effluxes ferrous iron and protects Bacillus subtilis against iron intoxication.
Iron is an essential element for nearly all cells and limited iron availability often restricts growth. However, excess iron can also be deleterious, particularly when cells expressing high affinity iron uptake systems transition to iron rich environments. Bacillus subtilis expresses numerous iron importers, but iron efflux has not been reported. Here, we describe the B. subtilis PfeT protein (formerly YkvW/ZosA) as a P1B4 -type ATPase in the PerR regulon that serves as an Fe(II) efflux pump and protects cells against iron intoxication. Iron and manganese homeostasis in B. subtilis are closely intertwined: a pfeT mutant is iron sensitive, and this sensitivity can be suppressed by low levels of Mn(II). Conversely, a pfeT mutant is more resistant to Mn(II) overload. In vitro, the PfeT ATPase is activated by both Fe(II) and Co(II), although only Fe(II) efflux is physiologically relevant in wild-type cells, and null mutants accumulate elevated levels of intracellular iron. Genetic studies indicate that PfeT together with the ferric uptake repressor (Fur) cooperate to prevent iron intoxication, with iron sequestration by the MrgA mini-ferritin playing a secondary role. Protection against iron toxicity may also be a key role for related P1B4 -type ATPases previously implicated in bacterial pathogenesis.
Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.|State Key Laboratories for Agro-biotechnology and College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Guohua
G
Guan
Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
Azul
A
Pinochet-Barros
Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
Ahmed
A
Gaballa
Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
Sarju J
SJ
Patel
Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
José M
JM
Argüello
Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
John D
http://orcid.org/0000-0002-3832-3249
JD
Helmann
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D001412:Bacillus subtilis / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism / Q000633:toxicity*; D008345:Manganese / Q000378:metabolism; D009154:Mutation; D018085:Regulon; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D008345:Manganese; D007501:Iron; D000251:Adenosine Triphosphatases