PIPages
Labs

Michael Johnson

University of Arizona, AZ·Microbiology & Immunology

Bacteria that infect people fight the host for metals. Roughly 40% of proteins need a metal to work.

Fields

Microbiology & Immunology

Biochemistry

Topics

copper toxicity

zinc toxicity

metal homeostasis

Grants
1 known grant, through Jun 2029

What they work on

  1. Measure how Streptococcus pneumoniae changes its gene activity and metabolite levels across a range of copper and zinc concentrations, using transcriptomics and metabolomics in a minimal, host-like growth medium.
  2. Determine how copper and zinc uptake, export and internal metal levels (the metallome) shape the bacterium's gene and metabolite responses, and when each response system switches on.
  3. Test whether transcription factors, proteins that switch genes on or off, are mismetallated by copper or zinc in ways that rewire gene regulation in S. pneumoniae.
  4. Determine whether pathways affected by metal stress are poisoned by copper or zinc or used to resist them, by comparing metabolite levels with gene activity, and assess effects on transport of other metals.

More about the research

The human body tries to starve invading bacteria of helpful metals such as iron, manganese and calcium, while flooding them with copper and zinc, which are toxic to bacteria even at low levels. A further problem is mismetallation: the wrong metal binds a protein and weakens it, and copper binds most tightly of all. How bacteria sense and respond to combined copper and zinc stress, and to the changing amounts they meet inside the host, is still largely unknown.

Why it matters

Copper and zinc are part of the body's natural defense against bacterial infection. Learning which systems Streptococcus pneumoniae uses to survive metal stress, and which systems the metals damage, could point to weak spots in a common cause of pneumonia. That knowledge could eventually inform new ways to fight bacterial infections.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Elucidating the Orchestrated Bacterial Response to Copper Toxicity

NIH · Jul 2018 – Jun 2029

Closest labs

Daren Knoell

University of Nebraska Medical Center, NE·Microbiology & Immunology

Determine how loss of the zinc transporter ZIP8 alters the makeup of myeloid immune cells in the lung in mice, and what that means for clearing Streptococcus pneumoniae and for survival.

Amali Samarasinghe

University of Wisconsin-Madison, WI·Microbiology & Immunology

Determine how eosinophils, allergy-associated white blood cells, take up and kill Streptococcus pneumoniae inside and outside the cell, and how taking up the bacteria changes the eosinophils' physiology and features.

Ryan Peterson

Texas State University, TX·Microbiology & Immunology

Identify and characterize the copper-binding metallophore that Pseudogymnoascus destructans secretes under copper limitation, testing the hypothesis that it is an opine-based metallophore, a class previously known only in bacteria.

The school

University of Arizona: 36 labs on PI Pages, $1.0B a year on research, 487 research doctorates a year.

More about University of Arizona

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