RALEIGH – Researchers from North Carolina State University have found a very high prevalence of Bartonella bacteria in tumors and tissues – but not blood samples – taken from dogs with hemangiosarcoma, a cancer of the blood vessels. The work further supports the connection between persistent infection and some types of cancer and adds to the evidence that Bartonella can remain and thrive, undetected, within tissue.
Hemangiosarcoma (HSA) is an aggressive, deadly cancer that arises from cells lining the blood vessels. It is responsible for two-thirds of all heart or splenic tumors in dogs, and is most common in medium-sized and middle-aged dogs. Since HSA usually cannot be diagnosed without major abdominal surgery, most HSA remains undetected until it has reached an advanced stage, resulting in a one-year survival rate of only 12 to 20%.
“There are clear precedents for the involvement of bacterial infections in tumor development,” says Ed Breitschwerdt, Melanie S. Steele Distinguished Professor of Medicine at NC State’s College of Veterinary Medicine and corresponding author of a paper describing the work. “Given the established links between chronic inflammation and cancer, we wanted to determine whether chronic infection of blood vessels due to bacteria could be a contributing cause of this cancer.”
Profile: Who is Ed Breitschwerdt?
Ed Breitschwerdt is one of the world’s leading experts on bartonellosis, a group of global zoonotic diseases caused by Bartonella bacteria.
His work on Bartonella threads back to 1982, when he joined NC State’s College of Veterinary Medicine (CVM) as an internist, specializing in companion animal internal medicine. After clinically encountering a plethora of unusual infectious diseases, he began investigating vector-borne infectious diseases such as Rocky Mountain spotted fever, a prevalent, potentially fatal disease of dogs and humans in North Carolina. To study this highly virulent bacterial pathogen, he established a biosafety level 3 (BSL-3) laboratory at CVM, and also started working with David Walker, a leading expert on spotted fever, and Willy Burgdorfer, a Swiss medical entomologist who discovered the bacteria responsible for Lyme disease.
Since 1992, when he and his PhD student began work on Bartonella in cats, Breitschwerdt’s research has expanded to dogs, marine mammals, horses and humans. Despite initial beliefs that Bartonella infections were rare and geographically restricted, Breitschwerdt, his collaborators and other scientists worldwide have now identified more than 40 Bartonella species. Using serological and molecular diagnostic modalities developed at NC State, his research team continues to assist with animal and human bartonellosis case studies worldwide.
Today, in addition to the multi-user BSL-3 Laboratory within the Comparative Medicine Institute at CVM, Breitschwerdt directs the Intracellular Pathogens Research Laboratory, and co-directs the Vector-Borne Disease Diagnostics Laboratory with Adam Birkenheuer and Barbara Qurollo. He also co-founded Galaxy Diagnostics, a CLIA certified laboratory that uses NC State technology to diagnose Bartonella infections in animals and human patients. In conjunction with Sushama Sontakke, he holds a US patent for enrichment culture media that Ricardo Maggi has optimized for the diagnosis of pathogens such as Bartonella, which are notoriously difficult to grow using conventional microbiological techniques.
With more than 25 years of experience in Bartonella research, Breitschwerdt has become a global contact for veterinary and human medical clinicians. He and his team continue to test animal and human samples from around the world, and provide diagnostic consultations on a daily basis. Together, their ultimate research goal is further improvements in diagnostic testing modalities for Bartonella infections, and development of a vaccine to prevent transmission of Bartonella spp. among vectors, animals and humans worldwide.
Breitschwerdt and colleagues from NC State looked at tumor tissue, non-tumor tissue and blood samples from 110 dogs with HSA from across the U.S. They screened both the tissues and the blood for Bartonella, Babesia, and Mycoplasma, three bacteria associated specifically with blood infections.
Bartonella DNA was amplified and sequenced from 80 of the dogs with HSA: it was present in 34% of tumor tissue and 63% of non-tumor tissue, but appeared in none of the blood samples. Mycoplasma DNA was only amplified from 5 of the dogs and Babesia wasn’t detected in any dog.
“Research in recent years has confirmed that persistent infection with or inflammation caused by stealth pathogens is a risk factor for developing cancer later in life,” Breitschwerdt says. “With the exception of Helicobacter pylori, the emphasis on evaluating the relationship between infection and cancer has focused on viruses. But intracellular bacterial pathogens such as Bartonella may also play an important and previously uninvestigated role.
“Bartonella is a stealth pathogen – it can ‘hide’ in the cells that line blood vessel walls, which is part of what makes it so difficult to detect,” Breitschwerdt says. “This work adds more evidence to the connection between infection and cancer risk, and demonstrates that molecular testing of whole blood samples does not rule out the tissue presence of this pathogen. Future studies are needed to investigate whether Bartonella infection can be a cause of HSA. Our team will be focusing on creating more sensitive diagnostic testing as part of this effort.”
The work appears in PLOS ONE and was supported by the American Kennel Club Canine Health Foundation (Grant 2519) and the Comparative Medicine and Translational Research Program of the National Institutes of Health (T32OD011130). Ph.D. student Erin Lashnits is first author.