Skip to main content

Institute of Human Virology Researchers Discover That a Bacterial Protein Promotes Cancer

December 04, 2018 | Nora Samaranayake

Research Suggests that Bacterial Infections May Contribute Far More to Cancers Than Previously Thought

The Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) announced today the discovery that DnaK, a protein of the bacterium mycoplasma, interferes with the mycoplasma-infected cell’s ability to respond to and repair DNA damage, a known origin of cancer.

Members of this research team include those pictured here: Fiorenza Cocchi, MD, Francesca Benedetti, PhD, Davide Zella, PhD, Robert Gallo, MD, Sabrina Curreli, PhD, and Selvi Krishnan, PhD

Little or no mycoplasma DnaK DNA sequences were found associated with the tumor, which was fully developed, suggesting a hit-and-run or hide mechanism of transformation, indicating that the damage is done early, but the protein may not be needed once the cancer cells are formed.

The study was published in the Proceedings of the National Academy of Sciences and suggests that bacterial infections may contribute to far more cancers than previously thought. The announcement was made by Robert Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine and Co-Founder and Director, Institute of Human Virology, University of Maryland School of Medicine and Davide Zella, PhD, Assistant Professor of Biochemistry and Molecular Biology, Institute of Human Virology, University of Maryland School of Medicine. Drs. Gallo and Zella collaborated with Hervé Tettelin, PhD, Associate Professor of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine.

“Currently, approximately 20% of cancers are thought to be caused by infection, most are known to be due to viruses,” said Dr. Gallo. who is also Co-Founder and Director of the Global Virus Network. “Mycoplasmas are a family of bacteria that are associated with cancers, especially in people with HIV. Our work provides an explanation for how a bacterial infection can trigger a series of events that lead to cancer. Of particular importance, the infection did not need to persist and the protein did not need to be continuously present in all cancer cells. The study also provides a mechanism for how some bacterial infections can interfere with specific cancer drugs.”

Researchers utilized immune-compromised mice as a model for analyzing the effect of mycoplasma infection on the development of lymphoma. They compared how quickly non-infected immune-compromised mice developed lymphoma compared to mycoplasma-infected immune-compromised mice. The mice were infected with a strain of mycoplasma from an HIV patient. The researchers found that mycoplasma infection caused the mice to develop lymphoma earlier in life than non-infected immune-compromised mice and that some, but not all, of the cancer cells had bacterial DNA. Finding only a small amount of bacterial DNA in the cancer cells suggested that the infection did not have to persist to trigger cancer.

“We focused on a protein called DnaK, which is part of a family of proteins that function as a ‘chaperone’ for other proteins protecting them from damage or helping them to fold,” said Dr. Zella. “However, in this case, DnaK reduces the activity of important cellular proteins involved in DNA repair and anti-cancer-activities, such as p53. Thus, cells infected with mycoplasma would not be able to properly repair damaged DNA, thus, potentially increasing the risk for cancer development.”

The scientists noted that the bacteria can release DnaK and the DnaK enters nearby uninfected cells. The study also demonstrates that by reducing p53, DnaK can also reduce the efficacy of anti-cancer drugs. Thus, mycoplasma infection could not only trigger events leading to the accumulation of DNA damage and oncogenesis in infected cells, but also trigger cancer-causing events in nearby uninfected cells that took up DnaK released from infected neighboring cells.

“We analyzed the amino acid sequences of DnaK from many bacteria and found that the DnaK proteins from bacteria associated with cancer grouped together were different DnaK sequences from bacteria that are not associated with cancer,” said Dr. Tettelin. “This raises the possibility that other bacteria have the same cancer-promoting ability.

According to Dr. Gallo, “This hit-and-run, or hide, mechanism mediated by a protein common to many cancer-associated bacteria changes how we need to think about infection and at least some cancers. Furthermore, this provides a basis for understanding how infection can influence the effectiveness of some cancer treatments.”

“This is fascinating science with important implications,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. “We are pleased to see a cross-collaboration between two disciplines here at the University of Maryland School of Medicine. Our Institute of Human Virology’s basic science laboratory research was aided by the School’s Institute of Genome Sciences’ sequencing expertise, bringing the research to full fruition.”

This research was partially funded by the Maryland Cigarette Restitution Fund (CRF) Program. Morgan State University also participated in this study.

About the Institute of Human Virology

Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland and the University of Maryland Medical System, IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders - most notably, HIV the virus that causes AIDS. For more information, www.ihv.org and follow us on Twitter @IHVmaryland.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Laser Award in Medical Research. With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically-based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and more than $530 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu/

Contact

Institute of Human Virology
Nora Samaranayake
Director of Marketing and Public Relations
(410) 706-8614 (phone)
(410) 706-1952 (fax)
nsamaranayake@ihv.umaryland.edu

Related stories

    Wednesday, September 19, 2018

    Institute of Human Virology (IHV) Awarded $12M to Combat Opioid Epidemic Through Clinical Research Trials

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine will lead a $12 million dollar project to improve the morbidity and mortality of people with opioid use disorder (OUD). Utilizing a novel compound, IHV researches will implement a series of investigations, entitled SEARCH, to evaluate the underlying mechanisms of craving reduction as a strategy to prevent opioid misuse, dependence, and relapse. The grant is awarded through the National Institutes of Health’s (NIH) Helping to End Addiction Long-term (HEAL) Initiative, made possible through groundbreaking funding from the U.S. Congress.


    Wednesday, March 21, 2018

    Dr. Robert Redfield, Co-Founder of the Institute of Human Virology at the University of Maryland School of Medicine, to Become CDC Director

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) congratulates its co-founder and associate director, Robert R. Redfield, MD, on his appointment to be the next director of the U.S. Centers for Disease Control and Prevention (CDC).


    Tuesday, March 20, 2018

    UMSOM Cancer Expert at Institute of Human Virology Named Fellow of American Society of Clinical Oncology

    Clement A. Adebamowo, BM, ChB, ScD, FWACS, FACS, Associate Director of Population Science at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine (UMSOM), and Professor of Epidemiology and Public Health, Institute of Human Virology, has been named a 2018 Fellow of the American Society of Clinical Oncology (ASCO).


    Wednesday, November 29, 2017

    To Mark World AIDS Day, Institute of Human Virology Releases Video on Dr. Robert Gallo

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine (UMSOM) released a video on Dr. Robert Gallo, a trailblazer in HIV research, in advance of World AIDS Day, December 1. While many know Dr. Gallo for his pioneering work in AIDS research, the short video focuses on Dr. Gallo’s life and legacy in its entirety, including his pioneering discovery of human retroviruses.


    Tuesday, November 22, 2016

    IHV Awarded $138M to combat HIV/AIDS in Africa & Launches Center for International Health, Education, & Biosecurity

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine announced today more than $138 million in multiple five-year grants awarded by the Centers for Disease Control and Prevention to combat HIV/AIDS in Kenya, Tanzania, Zambia, and Nigeria. The Institute concurrently announced the formation of the IHV Center for International Health, Education, & Biosecurity (CIHEB), and its newly appointed director, Deus Bazira Mubangizi, DrPH, MBA, MPH, Assistant Professor of Medicine, Director, Center for Health, Education, & Biosecurity, Institute of Human Virology, University of Maryland School of Medicine.


    Tuesday, October 25, 2016

    "A Call to End HIV/AIDS in America" IHV Director Dr. Robert Gallo's Op-Ed in the Huffington Post

    As the new Administration is presented with great challenges facing the United States, one will be a longtime foe, the U.S. HIV/AIDS epidemic. Since President Barack Obama was elected in 2008, I have publicly called on our country’s leaders to utilize the largest global health initiative in history - the President’s Emergency Plan for AIDS Relief (PEPFAR) - as a model to address the U.S. epidemic.


    Monday, August 22, 2016

    Institute of Human Virology (IHV) Awarded $14.4M for HIV Vaccine Research

    The Institute of Human Virology (IHV) announced a $14.4M grant from NIAID to advance HIV vaccine research to solve a major challenge: produce long-lasting antibodies to protect against HIV infection.


    Wednesday, April 13, 2016

    IHV Releases Data Supporting Community-Based Treatment Providers in Fight Against Hepatitis C

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine released data today at The International Liver Congress 2016 in Barcelona, Spain demonstrating that treatment for hepatitis C virus (HCV) can be provided safely and effectively within a community-based and non-specialist setting.


    Thursday, March 10, 2016

    UM SOM Establishes Two Endowed Professorships Through Private Gifts and Matching State Funds

    University of Maryland School of Medicine (UM SOM) Dean E. Albert Reece, MD, PhD, MBA, announced today that the School has been awarded matching funds from the Maryland Department of Business and Economic Development (DBED) as part of the Maryland E-Nnovation Initiative Fund program. The funds, when combined with private philanthropy, will enable UM SOM to establish two new endowed professorships – one in human virology and vaccine development, the other in surgical science and entrepreneurship.


    Tuesday, December 01, 2015

    A Statement from the Leadership of the Institute of Human Virology on World AIDS Day

    Research enabled treatment to be developed for HIV/AIDS, allowing the Institute of Human Virology (IHV) at the University of Maryland School of Medicine (which Dr. Gallo heads and co-founded with his colleagues Drs. William Blattner and Robert Redfield) to develop a promising HIV vaccine candidate, treat nearly 6,000 patients annually in Baltimore, and care for more than 1 million people in Africa and the Caribbean since 2004.


    Tuesday, September 29, 2015

    Institute of Human Virology Hosts International Meeting of Prominent AIDS Researchers

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine is hosting IHV’s 17th Annual International Meeting Sunday, September 27 through Wednesday, September 30 at the Baltimore Marriott Waterfront Hotel in Baltimore, Maryland.


    Tuesday, June 23, 2015

    Institute of Human Virology (IHV) Awarded $24.5M to Fight Botswana’s AIDS Epidemic

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine has received a five-year $24.5 million grant from the U.S. Centers for Disease Control and Prevention (CDC) through the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) to partner with the Government of Botswana and impact the HIV/AIDS epidemic in Botswana, and to demonstrate that comprehensive HIV/AIDS treatment programs can stop the epidemic. PEPFAR is a $48 billion initiative launched in 2004 by former President George W. Bush, and continued by President Barack Obama, to combat major infectious diseases around the world, including HIV.


    Thursday, April 02, 2015

    IHV Awarded $50 Million to Combat HIV Crisis in Zambia

    The Institute of Human Virology (IHV) at the University of Maryland School of Medicine received a $50 million five year grant from the President’s Emergency Plan for AIDS Relief (PEPFAR) to support the program, “Stop Mother and Child HIV Transmission” in Zambia. PEPFAR is a $48 billion initiative launched in 2004 by former President George W. Bush and continued by President Barack Obama. The announcement was made on the heels of IHV reaching the 1 million mark in care for HIV patients overseas.