Press Release
November 20, 2024
An innovative antibiotic for drug-resistant bacteria
“In Vivo Activity Profiling of Biosynthetic Darobactin D22 against Critical Gram-Negative Pathogens”
ACS Infectious Diseases
Antibacterial drugs are important for treating infections. But increasingly, bacterial resistance to current drugs — so they don’t work well, or even at all — means new ones are urgently needed. Building on previous work, researchers in ACS Infectious Diseases have demonstrated a potential antibacterial treatment from a modified darobactin, a compound originally from a bacterium. The team reports proof-of-concept animal trials on infections caused by bacteria, including E. coli, that are known to develop drug resistance.
A new antibacterial approach targets treatment-resistant bacteria, such as E. coli, that are categorized as a priority by the World Health Organization.
Saiful52/Shutterstock.com
This study was published during the World Health Organization’s World Antimicrobial Resistance (AMR) Awareness Week from November 18 to 24.
Earlier in 2024, the World Health Organization updated its list of bacterial pathogens that can develop resistance to antibiotics to include Acinetobacter baumannii, Pseudomonas aeruginosa and E. coli, among others. Despite the need for new antibiotics that target these priority pathogens, scientists don’t have many candidates. One potential resistance-breaking compound is called darobactin, a naturally produced antibiotic discovered in a bacterium. Darobactin binds to an essential protein in cells of different bacteria and eventually causes their death. Previously, Rolf Müller, Jennifer Herrmann and colleagues showed that genetically engineered versions of darobactin have antibacterial activity. Specifically, one of these non-natural, biosynthetic darobactins (called D22) inhibited A. baumannii growth in lab assays.
For this new study, a larger team led by Müller and Herrmann tested the engineered D22 compound against several priority bacterial infections in animals. First, in zebrafish embryos, D22 treatment cleared A. baumannii infection as effectively as ciprofloxacin, a broad-spectrum antibiotic used for complicated infections. Then the team conducted a series of efficacy and dosing trials with mice:
- Best delivery method: Observations indicated that administering D22 as an injection was more effective than via mouth.
- Efficacy against P. aeruginosa: Repeated doses of D22 substantially limited P. aeruginosa bacterial growth in mice (thigh tissue infection) but didn’t fully clear the infection.
- Multi-dose experiments against E. coli: Administering D22 four times in 25 hours fully cleared E. coli in a severe infection model of peritonitis (abdomen infection). Activity was also observed for single doses. Twice-daily D22 injections over three days significantly reduced bacterial presence in a complicated E. coli urinary tract infection, although not as low as the antibiotic gentamicin, which reduced bacterial loads below detection.
These results show that D22 can inhibit critical infections and highlights the compound’s promise for further development toward future clinical trials as “an innovative solution to fight antimicrobial resistance,” say the researchers.
The authors acknowledge funding from the Helmholtz Impuls- und Vernetzungsfonds (Impulse and Networking Fund).
Some of the authors are employees of Evotec, a biotechnology company involved in drug discovery and development.
The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, e-books and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio. www.acs.org
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American Chemical Society (ACS)
Source: https://www.acs.org/pressroom/presspacs/2024/november/an-innovative-antibiotic-for-drug-resistant-bacteria.html
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American Chemical Society (ACS)
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