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Why Don’t We Respect Bacteria? First Symposium on Bacterial Resistance at Wistar

August 13, 2019

There is an antibiotic crunch happening globally and to address this stalemate, Wistar hosted its first gathering of top scientists working to combat antibiotic resistance. 

The recent U.K. Review on Antimicrobial Resistance outlines the growth in this problem. It predicts an increase in deaths from antimicrobial resistant (AMR) infections from 700,000 per year today, to approximately 10 million per year over the next 30 years, and that the global economic cost of AMR could reach $100 trillion dollars by 2050. 

Bacterial infections are increasingly resistant to our world collection of antibiotics, which were once our best line of defense. Many of these drugs are no longer effective for treating those same infections, and instead are leading to increasingly drug-resistant diseases, even “superbugs.” 

Wistar recently held a scientific symposium to bring experts together and share in the latest discoveries to combat AMR. The Gram-negative Bacterial Resistance Symposium, supported by Pfizer Inc., was one of the few academic-industry conferences exchanging and exploring new ideas to fighting AMR. It featured leaders from across the nation, including Wistar’s very own Drs. David Weiner, Farokh Dotiwala and Ami Patel who spoke to this “post-antibiotic” era we have entered, and provided a vision of new approaches to head off this growing concern.   

Bacteria – A Global Threat

Bacteria are classified into gram-positive and gram-negative, with gram-negative being more resistant to antibiotics due to a thicker, protective outer membrane as well as containing many internal “pump” proteins that recognize and pump out toxic drugs, allowing them to escape the effects of many current antibiotics. Of the top 10 global AMR threats, seven are gram-negative organisms. The top three most deadly threats are gram-negative infections.   

“The World Health Organization lists antibiotic resistance as one of the biggest threats to global health,” said Weiner, executive vice president, director of the Vaccine & Immunotherapy Center and W.W. Smith Charitable Trust Professor in Cancer Research at Wistar, during his opening address. “This topic is central now. For your attendance you have an assignment: We can no longer follow what has been done before, but must lead with new approaches and strategies against gram-negative pathogens!”  

Throughout the day, researchers shared challenges and solutions to better understand multidrug-resistant strains like Acinetobacter baumannii (Iraqibacter), Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli (E. coli), malaria, salmonella, shigella, and gonorrhea.

Presenters like Dotiwala, assistant professor in the Vaccine & Immunotherapy Center at Wistar, are thinking outside the box to find new approaches to getting inside gram-negative bacteria and successfully delivering a new type of drug.

Dotiwala is working on a novel class of antibiotics that would target a niche in bacterial enzymes to kill the bacteria and activate the immune system. His research will lead to highly specific antimicrobial strategies against antibiotic-resistant strains as well as promising anti-cancer immunotherapies.

Patel, a research assistant professor in Wistar’s Vaccine & Immunotherapy Center and a collaborator with the Weiner lab, is applying her research developing synthetic DNA vaccines and synthetic DNA-based monoclonal antibodies (DMAbs) to numerous infectious diseases with the hope of moving new therapies forward. 

Patel discussed how the synthetic DNA platform has the potential to prevent and improve recovery from AMR infections of Pseudomonas aeruginosa, an opportunistic organism that is a serious threat in immunocompromised people. In a hospital setting, it is easily spread and can cause pneumonia, blood infections and urinary tract infections. 

Upon closing the symposium with a panel discussion, Dr. Paul Offit, director of the Vaccine Education Center and attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia, said “The post antibiotic era looks like the pre-antibiotic era.” 

He then held up the 1925 book Arrowsmith by Sinclair Lewis, a fictional story about a phage discovery that cures bubonic plague and saves a South American community. Offit asked the panelists what about bacteriophages as a commercial product are holding us back, at least as a personalized approach for patients with highly intractable diseases. All the panelists agreed that the challenges are great and numerous but, as this day showcased, many promising approaches are underway. 

Dr. Sanjay Ram, professor of Medicine at the University of Massachusetts Medical School, showed promising data targeting N. Gonorrheae with designed antibodies and DNA-encoded monoclonal antibodies and suggested they may be game changing. Dr. Daniel Zurawski, chief of Pathogenesis and Virulence at Walter Reed Army Institute of Research, discussed antibody technologies that may be of particular importance for AMR as they can be combined with traditional antibiotics and tested quickly to limit resistance. Dr. Kathrin Jansen, SVP and head of Vaccine Research & Development at Pfizer Inc., commented on vaccine approaches and how researchers should think in terms of personalized treatments and how new immune tools may be very useful. 

Emily Kramer-Golinkoff made an impassioned presentation to the attending researchers that bacteria resistance constitutes the single greatest threat to the Cystic Fibrosis (CF) community. She has advanced-stage CF and is the founder of Emily’s Entourage, a nonprofit that brings together research, patient, pharmaceutical, and biotech communities to raise funds and accelerate R&D development of therapies to benefit patients who carry nonsense mutations and do not respond to current and breakthrough drugs.

“I feel the pressure of time with every single breath I take,” said Emily. “I speak on behalf of myself and every single person fighting this disease. Our lives, our futures are on your shelves, in your hands, and you are the brilliant researchers uniquely capable of developing and shepherding our life-saving therapies through the pipeline and into clinic in record speed.” 

“There is always a human cost to medical breakthroughs, and we pay the highest human cost when we don’t take on the challenges,” concluded Offit.

Symposium on Gram-Negative Bacterial Resistance