Mis-annotations of a promising antibiotic target in high-priority gram-negative pathogens

Rachael E. Impey, Mihwa Lee, Daniel A. Hawkins, John Sutton, Santosh Panjikar, Matthew A. Perugini, Tatiana P. Soares da Costa

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The rise of antibiotic resistance combined with the lack of new products entering the market has led to bacterial infections becoming one of the biggest threats to global health. Therefore, there is an urgent need to identify novel antibiotic targets, such as dihydrodipicolinate synthase (DHDPS), an enzyme involved in the production of essential metabolites in cell wall and protein synthesis. Here, we utilised a 7-residue sequence motif to identify mis-annotation of multiple DHDPS genes in the high-priority Gram-negative bacteria Acinetobacter baumannii and Klebsiella pneumoniae. We subsequently confirmed these mis-annotations using a combination of enzyme kinetics and X-ray crystallography. Thus, this study highlights the need to ensure genes encoding promising drug targets, like DHDPS, are annotated correctly, especially for clinically important pathogens. PDB ID: 6UE0.

Original languageEnglish
Pages (from-to)1453-1463
Number of pages11
JournalFEBS Letters
Volume594
Issue number9
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • 4-hydroxy-tetrahydrodipicolinate synthase
  • antibiotic resistance
  • cell wall
  • diaminopimelate pathway
  • lysine

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