Novel Synthetic Antibiotic Designed To Overcome Antimicrobial Resistance Kills Pathogenic Superbugs

Some bacteria that can cause serious diseases are becoming more resistant to the commonly available antibiotics. These drug-immune pathogens can spread from one person to another within the community or from one patient to another in a hospital. The World Health Organization considers antibiotic resistance one of the biggest health threats worldwide.

Fight Against Superbugs

A team of researchers from Duke University has found a solution to fight gram-negative bacteria responsible for many urinary tract infections (UTIs). The study took decades of trial and error, looking for new strategies in defeating Salmonella, E. coli, and Pseudomonas.

The research focused on the development of synthetic molecules that can interfere with the ability of bacteria to create its outer lipid layer. According to lead author Pei Zhou, bacteria cannot survive without their outer membrane, so disrupting this membrane synthesis makes their compound very potent.

The small molecule LPC-233 effectively damaged the outer membrane lipid biosynthesis of every gram-negative bacterium used in the study. The researchers tested it on 285 bacterial strains, including those highly resistant to antibiotics, and the compound killed them all.

Aside from its effectiveness in killing pathogens, the molecule also works quickly. As described by Zhou, LPC-233 can reduce the viability of bacteria by 100,000-fold within just four hours. In terms of drug delivery, the compound can survive its journey through the urinary tract after being administered orally. This makes it a vital tool against tenacious urinary tract infections.

When LPC-233 was tested in animals, Zhou and his team administered the compound orally and intravenously to mice. The animals were given a fatal dose of the antibiotic-resistant bacteria, and the new compound rescued them from the infection.

The development of the molecule took decades because of the required specificity and safety of the synthetic compound. The search started in the 1980s when former Duke Biochemistry Chair Christian Raetz proposed a blueprint for the drug pathway. The rest of the team identified the enzyme that serves as the target of the new drug known as LpxC; it is the second enzyme in the "Raetz pathway," which plays a significant role in making the outer membrane lipid in gram-negative bacteria.

Health Impacts of Gram-Negative Bacteria

A gram-negative bacterium refers to many different types of bacteria that possess thin peptidoglycan cell walls covered by an outer membrane containing lipopolysaccharide. Its name was derived from their reaction to the Gram stain, a microbiological staining method used in identifying and characterizing bacteria.

Gram-negative bacteria possess strong cell walls, making them highly resistant to multiple drugs, especially most commercially available antibiotics. They can cause severe infections throughout the body, which can be hard to treat. Experts found that these microbes can discover new ways to resist antibiotics and pass along genetic materials, allowing other bacteria to become immune to drugs.

Some of the health problems brought by these bacteria include food poisoning, meningitis, wound infections, and sexually transmitted infections. They can also cause inflammation of the urinary tract, lungs, stomach, and intestines.

Check out more news and information on Gram-Negative Bacteria in Science Times.

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