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Scientists develop antibiotics against superbugs

Hong Kong scientists make major breakthrough in neutralizing drug-resistant superbugs.

Scientists in Hong Kong claim to have made a major medical breakthrough by developing a new family of antibiotics powerful enough to neutralize the superbugs that have spread worldwide and have been almost impossible to treat.

Bacteriologists at a university in Hong Kong claim they have developed a family of antibiotics powerful enough to neutralize multi-drug resistant superbugs, including methicillin-resistant Staphylococcus aureus, or MRSA.

MRSA refers to a group of genetically distinct bacteria pervasive in hospitals, nursing homes and even inside trains and buses in cities worldwide causing several difficult-to-treat infections.

There has been a decades-long global effort to fight MRSA and the search for new antibiotics to stem its spread has shown no progress since the superbugs’ emergence as early as the mid-1980s. People with open wounds or weakened immune systems are at greater risks of infection.

Bacterial drug resistance – public spaces and healthcare centers across the globe are now crawling with superbugs like MRSA – has been declared one of the biggest public health threats by World Health Organization Director-General Margaret Chan, who also served as Hong Kong’s public health chief.

In 2018, Hong Kong reported 1,218 cases of community-associated MRSA infections, a seven-fold jump compared with 2007, the year the first case was found in the city.

Researchers at the Hong Kong Polytechnic University (PolyU) said at a recent press conference that the novel small molecules they had just developed, based on new chemical structure and an antimicrobial mechanism, would be different from those of existing antibiotics incapable of sterilizing items with MRSA.

They claimed their new drug candidates demonstrated effective capabilities of inhibiting bacterial growth with no toxicity to human cells or tissues in numerous lab experiments.

The development and trial of the new class of antimicrobial agents, by PolyU’s Department of Applied Biology and Chemical Technology in partnership with the Chinese University of Hong Kong, is a potential breakthrough in the battle against MRSA.

“Our research is now at the end animal studies, conducting infectious model and pharmacokinetic observation and studies. These are the critical steps preceding clinical trials on humans for drug development,” said Dr Ma Cong, head of the research team.

“As a matter of fact, there are very few antibiotic-related studies among our peers abroad that are able to complete such a stage. Our findings so far are very promising … We believe further studies on these novel compounds will contribute to a new era of antibiotic discovery, contributing towards the fight against superbugs.”

Most antibiotics now in use function through disrupting the DNA synthesis or protein functions of harmful bacteria, while the new drug focuses on preventing the interaction between two proteins, NusB and NusE, which is crucial for synthesis of bacterial ribosomal ribonucleic acid and in turn bacterial cell proliferation.

The team developed a model based on the structure of the two proteins, and applied computer-aided screening to detect about 5,000 small molecule compounds with drug-like properties to act as inhibitors against protein interaction.

Some shortlisted compounds were then put to tests for antimicrobial effectiveness against different MRSA strains.

Test of the compounds on human lung and skin cells infected with MRSA indicated no significant toxicity. The fact that the two proteins exist only in bacteria and not in human cells has already addressed the toxicity concern, according to Dr Ma.

The research team has further structurally modified the compounds for optimization and named them “Nusbiarylins,” based on their target protein “NusB” and their “biaryl” structure.

Lab tests of Nusbiarylins against a panel of MRSA strains proved their consistent antibacterial effectiveness, much better than commonly used antibiotics including vancomycin, which is administered as the “last resort” antibiotic drug against superbugs in many Western countries.

Further pre-clinical studies on the in-vitro pharmacological properties of Nusbiarylins on human cells indicated that the compounds would not result in human blood cell breaking, an indication of being safe for injection, as well as excellent results in intestine absorption, meaning it is effective for oral taking.

The PolyU team won the “Global Innovation Award” at the TechConnect World Innovation Conference and Expo 2019 held in June in the United States.

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