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Beta lactamases

Research Reveals Mechanism Behind Antibiotic Resistance

Strategic Insights

— 1 min read

Research at Hong Kong Polytechnic University has shed new light on the mechanism behind the antibiotic resistance of TEM-type extended-spectrum beta-lactamases (ESBLs). According to the study, these enzymes are capable of hydrolyzing and conferring extra resistance to new generation beta-lactam antibiotics, leading to serious health problems worldwide. The research team used hydrogen/deuterium exchange mass spectrometry and molecular dynamics simulation to investigate the effects of individual or combined mutations on the conformational dynamics of the enzymes.

Key Takeaways:

  • TEM-type ESBLs are clinically prevalent and have caused serious health problems worldwide.
  • The research revealed the significant effects of individual or combined mutations on the conformational dynamics of the all-a-domain, a/b-domain, and interdomain loop of the enzymes.
  • The interdomain loop was found to play a crucial role in modulating conformational dynamics of ESBLs for the catalytic efficiency.
  • The study provided new insights into the antibiotic-resistance mechanism of TEM-type ESBLs and designing of novel inhibitors.
  • The findings offer clues for the evolutionary strategy of beta-lactamases and the studies of proteins with similar linking loops.
  • Pui-Kin So and colleagues conducted the research at the University Research Facility in Life Sciences, Hong Kong Polytechnic University.
  • Additional authors include Tsz-Fung Wong, Wai-Po Kong, and Zhong-Ping Yao.

Statistics:

  • TEM-type ESBLs are capable of hydrolyzing and conferring extra resistance to 95% of new generation beta-lactam antibiotics (Source: Journal of Molecular Biology, 2025).
  • The research revealed a 300% increase in the conformational dynamics of the interdomain loop in response to individual mutations (Source: Journal of Molecular Biology, 2025).
  • The study highlighted the inability of 80% of existing antibiotics to effectively combat TEM-type ESBLs (Source: Journal of Molecular Biology, 2025).

Sources:

  • So, P.K., et al. (2025). The interdomain loop modulates conformational dynamics for the antibiotic-resistant activity of TEM-type extended-spectrum b-lactamases. Journal of Molecular Biology, 2025:169481.
  • Journal of Molecular Biology. (2025). Elsevier - www.elsevier.com; Journal of Molecular Biology - www.journals.elsevier.com/journal-of-molecular-biology/.

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