Novel antibiotic activates 'suicide' mechanism in superbug

Researchers have discovered a new class of antibiotic that selectively targets Neisseria gonorrhoeae, the bacterium that causes gonorrhoea, by triggering a ‘self-destruction’ program. The research was led by Professor Christof Hauck from the University of Konstanz and Professor Thomas Böttcher from the University of Vienna, and has been published in the journal Nature Microbiology.

Last year, the World Health Organization (WHO) compiled a list of particularly problematic bacterial pathogens (the Bacterial Priority Pathogens List), naming 15 types of bacteria that are resistant to antibiotics and calling upon science and industry to focus their efforts on developing drugs that fight these microbes. One bacterium on the list is Neisseria gonorrhoeae, also referred to as gonococcus — a highly specialised type of bacteria that primarily colonises mucous membranes in the genital tract and can be transmitted from person to person during unprotected sex. During birth, these pathogens can also be transmitted from an infected mother to her child, causing the baby’s eyes to become infected.

“Gonococci are notorious for quickly becoming resistant to antibiotics,” Böttcher noted. This is because gonococci have the special ability to pick up genetic material from other microbes — including antibiotic resistance genes. “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,” Böttcher added.

Böttcher and Hauck’s teams have now been able to identify new substances from the group of alkyl quinolones (AQs) that are even effective against multidrug resistant gonococci. AQs are substances produced naturally by some bacteria to ward off other naturally occurring bacteria. Building on the idea that ‘the enemy of my enemy is my friend’, the researchers recreated these natural substances in the lab and synthesised slightly modified variants.

“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,” Hauck said.

The team elucidated the nature of this astonishing effect using an interdisciplinary research approach that combines synthetic and organic chemistry with genetic and biochemical analyses as well as complex preclinical animal models. It turned out that the 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,” said first author Ann-Kathrin Mix, a doctoral researcher in Hauck’s team.

The new antibiotic causes the breakdown of an antitoxin in gonococci, so that the toxin part is released and kills the bacteria. Importantly, the AQ substance can even eliminate multi-resistant gonococcal variants. However, since the respective toxin-antitoxin system is exclusive to gonococci, the antibiotic does not harm other bacteria.

Toxin-antitoxin systems are also present in other infectious microorganisms. The researchers thus expect that this type of treatment could be adapted for use against other bacterial pathogens.

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

Image caption: Neisseria gonorrhoeae, the bacterium that causes gonorrhoea. Image ©Christof Hauck