Newly Developed Antibiotic Shows Promising Results in Combatting Antibiotic-Resistant Superbug

The appearance of antibiotic resistance belongs to an expanding health crisis worldwide, so the fight against so-called ‘superbugs’has been a difficult frontier for healthcare experts around the globe. But now there’s a breakthrough against one such opponent: Acinetobacter baumannii. At times known as CRAB when resistant to antibiotics, this particular bacteria is able to result in serious lung, urinary tract and gastrointestinal infections. The Centers for Disease Control and Prevention pointed out the resistance of CRAB to carbapenems – a potent broad-spectrum antibiotic class.

A collaboration between Harvard University scientists and Hoffmann La Roche has resulted in the creation of an effective new antibiotic, zosurabalpin, that kills A. baumannii. “zosurabalpin is a new concept in both composition and mechanism of action,” said Dr Kenneth Bradley, global head of infectious disease discovery at Roche Pharma Research and Early Development. A. baumannii is a Gram-negative bacteria, traditionally covered with inner and outer membranes which offer protection from antibiotic attack.

How does it work?

The research involved determining and then purifying a substance that could penetrate these defences and eliminate the bacteria. Adhering to intensive testing to enhance the potency and security of numerous compounds, the team finally settled on one modified molecule. The mechanism of action of zosurabalpin is especially interesting ; it stops lipopolysaccharides from going to the exterior membrane of the bacterium which is essential because of its shape. This particular disruption causes an inner accumulation of these molecules, leading to a toxic environment within the bacteria cell which results in its demise.

Zosurabalpin has been evaluated against over 100 CRAB samples and is shown to reduce bacterial counts in CRAB induced pneumonia in mice. Additionally, it prevented the death of mice with bacterial caused sepsis. Zosurabalpin is currently in phase 1 clinical trials to demonstrate safety in humans.

Despite this promising advancement, antimicrobial resistance poses a worldwide public health risk primarily because of lack of effective therapies. Based on the CDC’s 2019 Antibiotic Resistance Threats Report, the United States alone witnesses over 2.8 million antimicrobial-resistant infections a year causing over 35,000 deaths.

The researchers point out that zosurabalpin is specific: It’s designed to attack only A. baumannii. Although such precision is a manifestation of the genius of the antibiotic design, additionally, it shows the need associated with a continued, multifarious strategy for creating remedies which can handle a wider spectrum of antibiotic-resistant pathogens.

Source:

Zampaloni, C., Mattei, P., Bleicher, K. et al. A novel antibiotic class targeting the lipopolysaccharide transporter. Nature (2024). https://doi.org/10.1038/s41586-023-06873-0