In a new approach to fighting bacterial pathogens, Johns Hopkins University researchers have developed a new antibiotic intended to fight tuberculosis and other drug-resistant infections.
Tuberculosis (TB) is the deadliest infectious disease in the world, according to the World Health Organization (WHO). While such lung infections are notoriously hard to treat and are becoming increasingly resistant to drugs, a team of researchers based at the Johns Hopkins University School of Medicine are developing a new antibiotic intended to cure TB and other tough-to-treat infections.
About 1.8 million people worldwide died due to TB in 2015, though the Centers for Disease Control and Prevention notes that little of that impact is felt in the United States, where last year only 9,563 cases of a global total of 10.4 million were reported. The majority of TB infections are concentrated in India, Indonesia, China, Nigeria, Pakistan, and South Africa, which together account for 60% of these infections. While an annual TB incidence decline of 1.5% shows that public health efforts are bringing some progress, meeting the WHO’s End TB Strategy goals will require an annual decline of at least 4%.
A new study from researchers at Johns Hopkins University highlights one of the biggest global challenges facing those fighting TB today: battling increasingly virulent Mycobacterium tuberculosis bacteria in the age of antibiotic resistance. Last year, about 480,000 individuals around the world came down with a multidrug-resistant form of TB, and recent reports indicate that these superbug strains of the pathogen are more widespread than previously thought. In addition, the first-line antibiotic medications such as isoniazid and rifampin, which health officials rely on to clear out these infections, are progressively becoming less effective against TB, leaving doctors have to rely on combination regimens to treat their patients. Today, forms of TB with resistance to isoniazid and rifampin, as well as other drugs, pose an enormous challenge in controlling the epidemic.
The study, published in Nature Chemical Biology, details the research team’s work in developing a new set of antibiotics to target drug-resistant forms of TB and other bacterial pathogens. Many antibiotics available today stop bacterial infections by targeting the DD-transpeptidase enzyme that bacteria need to create their cell walls. However, more than a decade ago, researchers discovered LD-transpeptidase, a second such enzyme that allows TB bacteria and others to survive in the presence of antibiotics. With these findings, the team conducting the current study worked with the beta-lactam antibiotic subclass carbapenems to develop new compounds from existing drugs. Bacterial culture tests showed that these new compounds effectively stopped wall building in LD-transpeptidase, even in bacterial species prone to antibiotic resistance. In mice infected with TB, the new carbapenem drug under development—known as biapenem–cleared the infection in the mice lungs without the use of any other antibiotics.
These new findings come as the cost of developing new drugs has reached prohibitive levels, creating a disincentive for drug makers to research new antibiotics. In addition, this has also created a lull in new treatments to fight bacterial infection at a time when they are needed the most. Study author and Johns Hopkins associate professor Gyanu Lamichhane, PhD, said that the problem is that drug developers make bigger returns on chronic disease drugs, such as those for diabetes, than they do on novel antibiotics. “Our group has very little funding,” Dr. Lamichhane told Contagion. “Despite this we are very passionate about developing new antibiotics and our passion is driven by the fact that this is a huge medical need and it needs to be done whether or not sponsors realize this. The fact that very few scientists work on this problem proves that very little resource has been allocated to this highly important medical issue.”
A lack of funding is hardly the only detractor in antibiotic development, added Dr. Lamichhane, noting the ever-present issue of antibiotic resistance. “This threat will always be there. By nature, bacteria will mutate themselves in an attempt to thrive in the presence of chemical threat. There is nothing anyone can do about this. The only way out is to keep innovating new drugs so that we are ahead of the bad bugs. Efforts to use antibiotics only when needed and judiciously can help extend life time but cannot stop pathogens from gaining resistance.”
He said that without an emphasis on innovating new antibiotics, our options against deadly infections will decrease. In a press release from Johns Hopkins, the study authors explained that their new treatment is designed to target specific bacteria and leave the natural beneficial microbiome intact, reducing side effects and limiting the chances of untargeted bacteria from developing resistance to the new drug.
As for when these new drugs can be seen in the field fighting TB infections, that all depends, said Dr. Lamichhane. “The timeline for deliverables in the clinic or the bedside will be determined by the support provided to continue the research and development of these compounds. We hope the National Institutes of Health and other sponsors will prioritize this and support our work.”