Finding The Achilles’ Heel Of Drug Resistant Bacteria

By screening a total of 50,240 small molecules, scientists discovered a compound that suppresses the ability of multidrug resistant bacteria to cause infection.

AsianScientist (Aug. 3, 2018) – A research group in Hong Kong has discovered a compound that can be used against multidrug resistant bacteria. They published their findings in the Proceedings of the National Academy of Sciences.

The indiscriminate use of antibiotics has resulted in the emergence of multidrug resistant (MDR) bacteria, including methicillin resistant Staphylococcus aureus (MRSA). Of even greater concern is the recent emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA), which has hyper-virulent properties and is able to infect healthy individuals living in the community.

The World Health Organization has declared antimicrobial resistance one of the biggest threats to global health. Alternate therapeutic strategies are urgently needed to treat and contain the spread of MDR bacteria.

In the present study, scientists at the University of Hong Kong and their collaborators at the University of British Columbia, Canada, have discovered a compound that simultaneously suppresses the production of multiple virulence factors in MRSA and CA-MRSA.

The researchers screened a total of 50,240 structurally diverse small molecules to identify compounds that reduce the virulence of MRSA. They also employed a combination of mutational studies, enzymatic assays and molecular modeling.

One compound, which the team named M21, was found to be effective at suppressing the production of multiple virulence factors in CA-MRSA and MRSA. In addition, the molecular target of M21 was identified to be a ClpP, a major virulence regulator in S. aureus. Deletion of the ClpP gene in S. aureus does not have much affect effect on the growth of the bacteria, but it greatly reduces the ability of the bacteria to infect and cause harm to a host.

The researchers validated their findings in animal models, showing that experimental animals treated with M21 were protected against a virulent strain of CA-MRSA and survived the infection. This work furthers the notion that MDR can be stopped by using small molecules to impair the genetic expression of multiple virulence factors.

The article can be found at: Gao et al. (2018) Suppression of Staphylococcus aureus Virulence by a Small-molecule Compound.


Source: University of Hong Kong; Photo: Shutterstock.
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