New Compound Fights Superbug Gonorrhea via Toxin-Antitoxin System

In recent years, the World Health Organization (WHO) has consistently raised alarms regarding the rise of antibiotic-resistant microbes. Multi-resistant bacteria pose a significant threat to the global healthcare system, potentially undermining one of modern medicine's most crucial therapeutic tools.

A research team from the University of Konstanz and the University of Vienna, in collaboration with other partners, has now discovered a highly effective compound that employs a novel mechanism to target a particularly challenging pathogen.

The remarkable results from the research team, led by Christof Hauck, Professor of Cell Biology at the University Of Konstanz, and Thomas Böttcher, a Professor of Microbial Biochemistry at the University of Vienna, have been published in Nature Microbiology.

Last year, the WHO compiled a list of particularly problematic bacterial pathogens (Bacterial Priority Pathogens List). It identifies 15 types of bacteria that exhibit antibiotic resistance and categorizes them into “critical,” “high,” and “medium” priority groups.

The WHO has urged the scientific community and industry to concentrate their efforts on developing treatments to combat these microbes. Among the bacteria listed is Neisseria gonorrhoeae, the pathogen responsible for the sexually transmitted infection of gonorrhea.

Superbug Gonococci

Neisseria gonorrhoeae, commonly known as gonococcus, is a highly specialized bacterium that exists solely in humans. This pathogen primarily colonizes the mucous membranes of the genital tract and can be transmitted through unprotected sexual contact.

Additionally, during childbirth, these pathogens can be passed from an infected mother to her child, leading to infections in the baby's eyes. Before the advent of antibiotics, this was a frequent cause of blindness in newborns.

“Gonococci are notorious for quickly becoming resistant to antibiotics,” stated chemist Thomas Böttcher. This rapid resistance is due to the gonococci's unique ability to acquire genetic material from other microbes, including genes that confer antibiotic resistance.

This is one of the reasons why gonococcal strains have recently emerged that are resistant to all antibiotics currently in use – such superbugs can no longer be treated with antibiotics.”

Thomas Böttcher, Faculty of Chemistry, University of Vienna

Interdisciplinary Research Approach Enables Breakthrough

The teams led by Hauck and Böttcher have successfully identified new compounds from the alkyl quinolones (AQs) group that are effective against multidrug-resistant gonococci. AQs are naturally produced substances by certain bacteria to fend off other bacteria.

Inspired by the concept that “the enemy of my enemy is my friend,” the researchers synthesized these natural compounds in the laboratory, creating slightly modified versions.

One of these new AQ molecules actually did have a unique effect: The chemical compound was able to kill gonococci without having a negative impact on other microorganisms or human cells.”

Christof Hauck, Professor, Cell Biology, University of Konstanz

The team investigated the nature of this remarkable effect through an interdisciplinary research approach that integrates synthetic and organic chemistry with genetic and biochemical analyses, as well as complex preclinical animal models.

The research revealed that this novel antibiotic activates an existing “suicide” mechanism in gonococci.

From other microorganisms, we know about such self-destruction programs based on toxin-antitoxin systems, and our AQ substance seems to precisely target this Achilles heel of gonococci.”

Ann-Kathrin Mix, Study First Author and Doctoral Researcher, University of Konstanz

The new antibiotic triggers the degradation of an antitoxin in gonococci, leading to the release of the toxin component, which ultimately kills the bacteria. Notably, the AQ compound can even eradicate multi-resistant gonococcal variants. Since the specific toxin-antitoxin system is unique to gonococci, the antibiotic does not adversely affect other bacterial species.

Toxin-antitoxin systems are also found in other infectious microorganisms. Consequently, the researchers anticipate that this treatment approach could be adapted for use against additional bacterial pathogens.

“The recently published findings open up a new and innovative way to fight pathogenic microbes before our arsenal of antibiotics is drained,” concluded Hauck.