ZnuA and zinc homeostasis in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a ubiquitous environmental bacterium and a clinically significant opportunistic human pathogen. Central to the ability of P. aeruginosa to colonise both environmental and host niches is the acquisition of zinc. Here we show that P. aeruginosa PAO1 acquires zinc via an ATP-binding cassette (ABC) permease in which ZnuA is the high affinity, zinc-specific binding protein. Zinc uptake in Gram-negative organisms predominantly occurs via an ABC permease, and consistent with this expectation a P. aeruginosa ΔznuA mutant strain showed an ~60% reduction in cellular zinc accumulation, while other metal ions were essentially unaffected. Despite the major reduction in zinc accumulation, minimal phenotypic differences were observed between the wild-type and ΔznuA mutant strains. However, the effect of zinc limitation on the transcriptome of P. aeruginosa PAO1 revealed significant changes in gene expression that enable adaptation to low-zinc conditions. Genes significantly up-regulated included non-zinc-requiring paralogs of zinc-dependent proteins and a number of novel import pathways associated with zinc acquisition. Collectively, this study provides new insight into the acquisition of zinc by P. aeruginosa PAO1, revealing a hitherto unrecognized complexity in zinc homeostasis that enables the bacterium to survive under zinc limitation.
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Victoria G
VG
Pederick
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Bart A
BA
Eijkelkamp
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Stephanie L
SL
Begg
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Miranda P
MP
Ween
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Lauren J
LJ
McAllister
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
James C
JC
Paton
Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Christopher A
CA
McDevitt
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D015536:Down-Regulation / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D044366:Transition Temperature; D015854:Up-Regulation / Q000187:drug effects; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D012269:Ribosomal Proteins; D015032:Zinc