Apr 17, 2017

Study finds amoeba “grazing,” killing bacteria usually protected by film 

- David Tenenbaum, Science Writer, University of Wisconsin -Madison

Bacteria have developed an uncountable number of chemistries, lifestyles, attacks and defenses through 2.5 billion years of evolution. One of the most impressive defenses is biofilm – a community of bacteria enmeshed in a matrix that protects against single-celled predators and antibiotics – chemicals evolved by competitors through the course of evolution, including other bacteria and fungi.

Now, a University of Wisconsin–Madison professor of bacteriology has shown the first proof that a certain group of amoeba called dictyostelids can penetrate biofilms and eat the bacteria within. “This is the first demonstration that dicty are able to feed on biofilm-enmeshed bacteria,” Marcin Filutowicz says.

In an article now online in the journal Protist, Filutowicz, first author Dean Sanders of the Wisconsin Institute for Discovery, and colleagues show time-lapse, microscopic movies proving the amoeba’s voracious appetite for five species of bacteria. In the study, the researchers pitted four types of amoeba called dictyostelium (dictys) against biofilm-forming bacteria that harm plants or humans. The target bacteria included:

Tara Solger, a graduate student from Iran, works with Polysphondylium amoeba in the lab of Marcin Filutowicz, a professor of bacteriology at UW–Madison. David Tenenbaum
Tara Solger, a graduate student from Iran, works with Polysphondylium amoeba in the lab of Marcin Filutowicz, a professor of bacteriology at UW–Madison. David Tenenbaum
  • Pseudomonas aeruginosa, a common, multi-drug resistant bacteria that afflicts people who have, for example, burns or cystic fibrosis;
  • Pseudomonas syringae, pathogen of beans;
  • Klebsiella oxytoca, cause of colitis and sepsis; and
  • Erwinia amylovora, cause of fire blight in apples and pears.

As expected, the results depended on the strain of dicty and species of bacteria; in several cases, the dictys completely obliterated a thriving biofilm containing millions of bacteria within a day or two. The study, Filutowicz says, “contains the first movies ever to show dicty cells moving into a biofilm and devouring the bacteria.”

Because they form a multi-cellular phase sometimes called a “slug,” dictys are sometimes called “social amoeba.”

Beyond the visual evidence, spore germination and the subsequent union of single-celled dictys into a multi-cellular “slug” both showed successful attacks against all four species of bacteria.

Filutowicz became interested in dictys after discovering a neglected archive of about 1,800 strains amassed by Kenneth Raper, a bacteriology colleague who started collecting the soil-borne microbes around the world in the 1930s. “Raper was the first to isolate dictys, but after he died, his life work was scattered around the department and neglected,” Filutowicz says.

Mitchell Nitschke, a research specialist from Sussex, Wisconsin, examines amoeba on a new microscope in the Filutowicz lab. Dictys grow fast enough to be seen in real time. David Tenenbaum
Mitchell Nitschke, a research specialist from Sussex, Wisconsin, examines amoeba on a new microscope in the Filutowicz lab. Dictys grow fast enough to be seen in real time. David Tenenbaum
Filutowicz was intrigued, but he knew very little about dictys. Then, the answer to his most fundamental question — “How do I grow them?” triggered a mental chain reaction. He found that Raper and his followers were feeding and growing dictys in the lab using bacterial prey, but nobody had apparently pursued their real-world potential as microbe hunters. “If you grow them on E coli [a common resident of the human intestine], I quickly realized, because dictys are not pathogenic, we might use them as a biological weapon against bacteria.”

Having previously started Conjugon, a company devoted to developing benign bacteria to defeat pathogenic microbes, Filutowicz says he was “attuned to biological approaches, which were unheard then, and so this idea fell on a very fertile mind.”

With bacteria becoming resistant to a growing number of antibiotics, that’s welcome news, although using a living organism may add complexity to the task of getting regulatory approval.

Since 2010, Filutowicz has learned a good deal about how dicty “graze” upon bacteria, and which ones they prefer. “We looked at how these cells dismantle biofilms, trying to understand what physical, chemical and mechanical forces deconstruct the biofilms, and how the dictys move in 3-D space. These are phagocytes, and they behave much like our own immune cells,” says Filutowicz.

His collaborator, Curtis Brandt, a professor of ophthalmology and visual science at UW–Madison, has produced promising results suggesting that the organisms are harmless to rodents, and is preparing to use dictys to fight bacterial keratitis, an eye infection, first in rodents and then in humans, in research supported by the National Institutes of Health.

“This medical application may not reach the clinic in my lifetime, but it has a lot of promise, and eventually we may be able to advance it in many other medical uses,” Filutowicz says.

In 2010, Filutowicz formed Amoebagone, to advance research into use of dictys, starting by trying to fight fire blight and other bacterial infections of fruit trees and vegetables; supported by the National Science Foundation.

Between the far-off human medical potential, and the near-term use in agriculture, Filutowicz is delightedly pulling on the thread left by Ken Raper’s beneficial microbes; licensed by the Wisconsin Alumni Research Foundation to AmoebaGone.

“To make a discovery, it needs some level of naiveté,” he says. “If you know too much, you immediately appreciate why things will not work, cannot work. Otherwise, if it was a good idea, people would have done it already. Colleagues said dictys behaved like human phagocytes, but they never mentioned harnessing them as biological controls. Every day I walk through the departmental hallway and read the inscription: “Discovery consists of seeing of what everybody has seen and thinking what nobody has thought. I was lucky enough to enter this as the foolish innocent."

 

News Article
Jan 15, 2017

Amebagone Receives SBIR Advance Award to match Phase II National Science Foundation Grant Award to Develop Treatments for Biological Pathogens of Pome Fruits and Vegetable Crops

- Madison, WI 

Amebagone Inc. was awarded a matching state grant for $75K by the Wisconsin Economic Development Corp, administered by the Center for Technology Commercialization.  This award is associated with a Phase II National Science Foundation Grant Award to Develop Treatments for Biological Pathogens of Pome Fruits and Vegetable Crop.  It will help pay for new patent filings associated with the work, for travel to partner sites, and for assistance with developing a plan to register products with the EPA. 

Cheryl Vickroy, President and CEO, gratefully accepted the award.  "Without the SBIR Advance State SBIR Match, we'd be unable to afford these activities that cannot be funded by the federal agency, but that are crucial for us to successfully commercialize our work.", said Vickroy.

Mar 01, 2016

Amebagone Inc. Receives Certification as a Qualified New Business Venture from the Wisconsin Economic Development Corporation

Madison, WI, March 2016 – Amebagone Inc. is eligible for tax credits for Wisconsin investors in the amount of $187,500 for investments made prior to April 2017 through the Wisconsin Economic Development Corporation’s (WEDC) Qualified New Business Venture (QNBV) program.

AmebaGone Inc. develops natural biocides, disinfectants and other treatments against bacterial pathogens resulting in economic loss in agriculture and potentially loss of life. Our natural predator organisms consume dead or dormant bacteria and bacteria enmeshed in biofilms, thereby helping thwart proliferation of antibacterial resistance.

WEDC’s QNBV program provides a 25% tax credit on investments in qualified early-stage businesses by eligible angel and venture fund investors. “This is an important milestone in the growth of Amebagone.”, says Cheryl Vickroy, President of Amebagone. “Our plans are to commercialize multiple sanitizers and disinfectants against agricultural bacterial pathogens causing loss of crops in Wisconsin and throughout the nation, including products aimed at cash crops crucial to the Wisconsin economy such as potatoes.” The certification term extends through March 31, 2017.

 

According to Aaron Hagar (WEDC’s vice president of entrepreneurship and innovation), the primary purpose of the QNBV Program is to foster the development of new, innovative companies, such as Amebagone, thereby creating opportunities for long-term growth and new job creation. In its 10-year history, the WEDC QNBV Program benefitted over 300 companies in their efforts to attract funding, grow and bring their innovative ideas to market.

 

About the Wisconsin Economic Development Corporation

The Wisconsin Economic Development Corporation (WEDC) leads economic development efforts for the state by advancing Wisconsin’s business climate. Together with more than 600 regional and local business development partners, it represents a highly responsive and coordinated network. Visit InWisconsin.com

 

About AmebaGone – AmebaGone is an early-stage biotechnology firm specializing in the development of biocontrol agents, disinfectants, and sanitizers and salves that effectively kill bacteria. AmebaGone is an S Corporation located in Madison WI. Each of AmebaGone’s projects and products showcases is our commitment to solving problems of bacterial resistance to conventional chemical antibiotics.

The development and commercialization of AmebaGone’s technology is supported by the Small Business Innovation Research / Small Business Technology Transfer (SBIR/STTR) programs of the National Science Foundation (Award No. IIP- 1534650) and the National Institutes of Health (Award No. 1 R41 EY024475-01A1). The work is also supported by an SBIR Advance matching grant from the Wisconsin Economic Development Corp. (WEDC) through the Center for Technology Commercialization (CTC) and a loan from the Madison Development Corporation (MDC). Find out more at http://www.amebagone.com.

For more information, please contact Cheryl Vickroy, President, at cvickroy@amebagone.com. ###

Copyright © 2016 AmebaGone. All rights reserved.  

Nov 03, 2015

Amebagone Inc. awarded National Science Foundation SBIR Phase II funding to develop natural biocides

Amebagone Inc. was awarded a Phase II Small Business Innovation Research (SBIR) grant from the National Science Foundation to develop natural biocides for treating bacterial pathogens in pome fruits and vegetable crops. This award follows a successfully completed Phase I project proving our approach effective in vitro and en planta against Erwinia Amylovora (E.a.) a pathogen that attacks apple and pear orchards.

Concerns about bacterial resistance resulted in a 2014 legislative ban on use of antibiotics in organic orchards, creating problems for growers.  Without effective solutions, growers will lose their organic status thus disrupting an established and growing industry.  AmebaGone is developing bio-control products that act like human immune cells to treat disease-causing infections in plants and people. Our approach completely consumes free-living AND dormant or persister bacterial cells including those encased in biofilms.

 

Our founder and Chief Scientific Officer (CSO),  Marcin Filutowicz, Ph.D. is a professor of bacteriology at the University of Wisconsin-Madison. He and Katarzyna Borys, Ph.D. first conceived of using a benign, soil-dwelling organism known as Dictyostelids (Dicty) as a natural predator of bacterial pathogens.  Their seminal work resulted in the issuance of two broad patents, now owned by the company covering multiple domains in agriculture, medicine, industry and beyond.  AmebaGone has licensed 3 collections of more than 3000 highly unique source material from many countries around the globe, much of which originated years ago (1936 and forward) and under conditions that no longer exist.  This allows us to develop highly specific point-source solutions.

The development and commercialization of AmebaGone’s technology is supported by the Small Business Innovation Research (SBIR) programs of the National Science Foundation (Award No. IIP- 1534650) and the National Institutes of Health (Award No. 1 R41 EY024475-01A1).  For the NIH, we are developing a treatment for Bacterial Keratitis, a serious eye infection that can cause loss of sight.  This work was also supported by a micro-grant from the Wisconsin Economic Development Corp. (WEDC) through the Center for Technology Commercialization (CTC). 

Mar 01, 2015

AmebaGone begins partnership with Dr. Curtis Brandt at the University of Wisconsin with Phase I STTR award from Natiional Institutes of Health.

In partnership with the University of Wisconsin, Dept. of Opthalmology department led by Dr. Curtis Brandt, AmebaGone has begun exploration of using Dictystelids as a treatment for bacterial eye infections that could result in loss of sight.  

This work is funded by a phase I Small Business Technology Transfer award underwritten by the National Eye Institute at the National Institues of Health.

Jan 01, 2015

AmebaGone incorporates as an S corporation

Effective January 1, 2015, AmebaGone is now an S Corporation registered in the state of Wisconsin.

Dec 14, 2014

AmebaGone executes license to Dicty collection of Dr. James Cavender of Ohio University.

AmebaGone has executed a licensing agreement with Dr. James Cavender of Ohio University for exclusive access to his collection of Dictystelids spanning the globe and curated since the 1930s.

Nov 07, 2014

AmebaGone executes exclusive license to Dicty collection at Shepherd University.

On November 1, 2014, AmebaGone executed an exclusive license to a robust collection of Dictystelids at Shepherd University in West Virgina.

Sep 24, 2014

AmebaGone's founder at the University of Wisconsin-Madison receives a grant from the State Economic Engagement and Development (SEED) Research Program titled "Reviving and screening Dictyostelid’s collection for new drug discovery and other commercial use at the firm.  

Jul 08, 2014

UW-Madison licenses Dr. Kenneth Raper's Archive (>2,000 Dicty strains) to Amebagone

May 06, 2014

Second US Patent issued to AmebaGone (8,715,641)

Apr 19, 2014

Wisconsin State Journal: "Finalists in the Biz Plan Contest include some familiar names."

News Article
Jan 30, 2014

US Patent Application No: 2014/0030,227

The present invention relates to amoebae (slime molds) and uses thereof. In particular, the present invention relates to the use of amoebae or their environmentally stable spores to treat microbial infections and other uses.

News Article
Jan 01, 2014

NSF Phase I SBIR awarded to AmebaGone

The National Sceince Foundation (NSF) has awarded a Phase I SBIR for just under $150K to AmebeGone LLC for its project titled "Biological treatment of orchards to combat fire blight (Erwina amylovora)".

Oct 08, 2013

US Patent Issued to AmebaGone

United States Patent no. 8,551,471 was issued to AmebaGone on Oct. 8, 2013 for "Therapeutic Amoeba and Uses Thereof."

News Article
Jan 17, 2012

University of Wisconsin College of Letters and Science: Amoeba biotherapy: "New approach to combat intractable bacterial infections"

Article in Grow Magazine.

News Article
Oct 01, 2011

Grow - Wisconsin's Magazine for the Life Sciences: "The Infection Eaters"

Grow Magazine | Marcin Filutowicz stumbled upon a potentially powerful biotherapy—using amoebas that feast on antibiotic-resistant bacteria to cure such ills as staph infections and diabetic ulcers.

News Article

Amebagone Inc. Receives Certification as a Qualified New Business Venture from the Wisconsin Economic Development Corporation

Madison, WI, March 2016 – Amebagone Inc. is eligible for tax credits for Wisconsin investors in the amount of $187,500 for investments made prior to April 2017 through the Wisconsin Economic Development Corporation’s (WEDC) Qualified New Business Venture (QNBV) program.

AmebaGone Inc. develops natural biocides, disinfectants and other treatments against bacterial pathogens resulting in economic loss in agriculture and potentially loss of life. Our natural predator organisms consume dead or dormant bacteria and bacteria enmeshed in biofilms, thereby helping thwart proliferation of antibacterial resistance.

WEDC’s QNBV program provides a 25% tax credit on investments in qualified early-stage businesses by eligible angel and venture fund investors. “This is an important milestone in the growth of Amebagone.”, says Cheryl Vickroy, President of Amebagone. “Our plans are to commercialize multiple sanitizers and disinfectants against agricultural bacterial pathogens causing loss of crops in Wisconsin and throughout the nation, including products aimed at cash crops crucial to the Wisconsin economy such as potatoes.” The certification term extends through March 31, 2017.

 

According to Aaron Hagar (WEDC’s vice president of entrepreneurship and innovation), the primary purpose of the QNBV Program is to foster the development of new, innovative companies, such as Amebagone, thereby creating opportunities for long-term growth and new job creation. In its 10-year history, the WEDC QNBV Program benefitted over 300 companies in their efforts to attract funding, grow and bring their innovative ideas to market.

 

About the Wisconsin Economic Development Corporation

The Wisconsin Economic Development Corporation (WEDC) leads economic development efforts for the state by advancing Wisconsin’s business climate. Together with more than 600 regional and local business development partners, it represents a highly responsive and coordinated network. Visit InWisconsin.com

 

About AmebaGone – AmebaGone is an early-stage biotechnology firm specializing in the development of biocontrol agents, disinfectants, and sanitizers and salves that effectively kill bacteria. AmebaGone is an S Corporation located in Madison WI. Each of AmebaGone’s projects and products showcases is our commitment to solving problems of bacterial resistance to conventional chemical antibiotics.

The development and commercialization of AmebaGone’s technology is supported by the Small Business Innovation Research / Small Business Technology Transfer (SBIR/STTR) programs of the National Science Foundation (Award No. IIP- 1534650) and the National Institutes of Health (Award No. 1 R41 EY024475-01A1). The work is also supported by an SBIR Advance matching grant from the Wisconsin Economic Development Corp. (WEDC) through the Center for Technology Commercialization (CTC) and a loan from the Madison Development Corporation (MDC). Find out more at http://www.amebagone.com.

For more information, please contact Cheryl Vickroy, President, at cvickroy@amebagone.com. ###

Copyright © 2016 AmebaGone. All rights reserved.