New Drug Candidate Targets Mycobacterium abscessus, a Tuberculosis Relative

Researchers at the Hackensack Meridian Center for Discovery and Innovation (CDI) have unveiled a novel drug candidate aimed at combating Mycobacterium abscessus, a dangerous pathogen closely related to tuberculosis (TB). This bacterium poses a significant threat, particularly to individuals with compromised immune systems and those suffering from specific lung ailments.

The research team conducted an extensive investigation into Mycobacterium abscessus, which has become a rising concern among cystic fibrosis patients. To address the limitations of traditional antibiotics, the researchers chemically modified a well-known rifamycin antibiotic to enhance its effectiveness against this resilient infection.

These findings were published in the Proceedings of the National Academy of Sciences, highlighting the collaborative efforts of Dr. Véronique Dartois and Dr. Thomas Dick from CDI, along with other researchers.

The rifamycin antibiotics, developed in the 1960s, have historically been effective against TB; however, M. abscessus exhibits a notable resistance to these medications. Additionally, the risk of drug interactions poses a significant challenge for patients, especially those with cystic fibrosis.

In response to these challenges, the research team employed a medicinal chemistry approach to create compounds that could overcome drug resistance while maintaining strong therapeutic activity and favorable pharmacokinetics. Over a five-year period, they synthesized various analogs of rifabutin that showed promise in targeting M. abscessus.

Out of the numerous compounds evaluated in laboratory and animal models, two candidates emerged as particularly effective against M. abscessus. These next-generation rifamycins also hold potential for treating other rapidly growing nontuberculous mycobacteria (NTM) and the Mycobacterium avium complex (MAC), in addition to TB.

As reported in the journal BMC Infectious Diseases, the prevalence of M. abscessus infections among cystic fibrosis patients has been increasing alarmingly. Ongoing research is investigating environmental factors, such as elevated levels of certain minerals in water supplies, that may contribute to the risk of NTM pulmonary infections in these individuals.

Dr. Dick noted that the groundwork for this research was laid nearly a decade ago at the National University of Singapore, with key contributions from various collaborators. He emphasized the importance of teamwork among academic researchers, students, and postdoctoral fellows in achieving this milestone.

The collaboration involved significant contributions from Dr. Courtney Aldrich and medicinal chemist Tian Lan at the University of Minnesota, as well as Dr. Mercedes Gonzales-Juarrero and her team at Colorado State University.

The researchers concluded that their work marks a significant advancement in the development of second-generation rifamycins, which possess enhanced efficacy and improved pharmacological properties against mycobacterial infections. This innovative drug candidate could play a critical role in addressing the growing threat posed by Mycobacterium abscessus.