Specific Amino Acid Substitutions in OXA-51-Type β-Lactamase Enhance Catalytic Activity to a Level Comparable to Carbapenemase OXA-23 and OXA-24/40

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Kwan-Wai Chan
  • Ho-Yin Wong
  • Wai-Chi Chan
  • Kwok-Yin Wong

Detail(s)

Original languageEnglish
Article number4496
Journal / PublicationInternational Journal of Molecular Sciences
Volume23
Issue number9
Online published19 Apr 2022
Publication statusPublished - May 2022

Link(s)

Abstract

The chromosomal blaOXA-51-type gene encodes carbapenem-hydrolyzing class D β-lactamases (CHDLs), specific variants shown to mediate carbapenem resistance in the Gram-negative bacterial pathogen Acinetobacter baumannii. This study aims to characterize the effect of key amino acid substitutions in OXA-51 variants of carbapenem-hydrolyzing class D β-lactamases (CHDLs) on substrate catalysis. Mutational and structural analyses indicated that each of the L167V, W222G, or I129L substitutions contributed to an increase in catalytic activity. The I129L mutation exhibited the most substantial effect. The combination of W222G and I129L substitutions exhibited an extremely strong catalytic enhancement effect in OXA-66, resulting in higher activity than OXA-23 and OXA24/40 against carbapenems. These findings suggested that specific arrangement of residues in these three important positions in the intrinsic OXA-51 type of enzyme can generate variants that are even more active than known CHDLs. Likewise, mutation leading to the W222M change also causes a significant increase in the catalytic activity of OXA-51. blaOXA-51 gene in A. baumannii may likely continue to evolve, generating mutant genes that encode carbapenemase with extremely strong catalytic activity.

Research Area(s)

  • A. baumannii, carbapenem resistance, carbapenem-hydrolyzing class D β-lactamases (CHDLs), OXA-51 variants, structure/function relationship

Citation Format(s)

Specific Amino Acid Substitutions in OXA-51-Type β-Lactamase Enhance Catalytic Activity to a Level Comparable to Carbapenemase OXA-23 and OXA-24/40. / Chan, Kwan-Wai; Liu, Chen-Yu; Wong, Ho-Yin; Chan, Wai-Chi; Wong, Kwok-Yin; Chen, Sheng.

In: International Journal of Molecular Sciences, Vol. 23, No. 9, 4496, 05.2022.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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