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Mis‐annotations of a promising antibiotic target in high‐priority gram‐negative pathogens
Author(s) -
Impey Rachael E.,
Lee Mihwa,
Hawkins Daniel A.,
Sutton J. Mark,
Panjikar Santosh,
Perugini Matthew A.,
Soares da Costa Tatiana P.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13733
Subject(s) - acinetobacter baumannii , klebsiella pneumoniae , gene , biology , bacteria , microbiology and biotechnology , antibiotics , computational biology , protein data bank (rcsb pdb) , enzyme , genetics , biochemistry , escherichia coli , pseudomonas aeruginosa
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 .