How Bacteria Resist Even Peptide Antibiotics

Scientists in Hong Kong have discovered how bacteria may become resistant to peptide antibiotics.

AsianScientist (Mar. 27, 2018) – A research group in Hong Kong has discovered a family of enzymes that makes bacteria resistant to a class of antibiotics known as non-ribosomal peptide antibiotics. They published their findings in Nature Chemical Biology.

Non-ribosomal peptide antibiotics, including polymyxin, vancomycin and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria.

However, overusing antibiotics while ignoring the risk of resistance arising has led to the widespread emergence of resistant bacteria. Elucidating the little-known mechanisms of resistance to peptide antibiotics is critical to ensure the long-term efficacy of such antimicrobials.

In the present study, a group of scientists from the Hong Kong University of Science and Technology revealed the widespread distribution and broad-spectrum resistance potential of D-stereospecific peptidases (DRPs), thus providing a potential early indicator of antibiotic resistance to non-ribosomal peptide antibiotics.

“We analyzed 5,585 complete bacterial genomes spanning the entire domain of bacteria,” said Professor Qian Pei-Yuan of Hong Kong University of Science and Technology, who led the research. “With subsequent chemical and enzymatic analyses, we demonstrated a mechanism of resistance toward non-ribosomal peptide antibiotics that is based on hydrolytic cleavage by DRPs.”

The team found that a family of DRPs is widely distributed in nature and known to be involved in the deactivation of commonly used antibiotics containing D-amino acids. Given the potential of DRPs for broad-spectrum resistance, the researchers warned that these widespread resistance genes could be particularly dangerous if they are transferred to opportunistic pathogens

“This discovery of DRPs in nature constitutes only the tip of the iceberg. [We hope our findings] will lead to further research on the use and development of peptide antibiotics to combat antibiotic resistance,” said Qian.

The article can be found at: Li et al. (2018) Resistance to Nonribosomal Peptide Antibiotics Mediated by D-stereospecific Peptidases.


Source: Hong Kong University of Science and Technology; Photo: Shutterstock.
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