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Three redundant murein endopeptidases catalyse an essential cleavage step in peptidoglycan synthesis of E scherichia coli K 12
Author(s) -
Singh Santosh Kumar,
SaiSree L.,
Amrutha Ravi N.,
Reddy Manjula
Publication year - 2012
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12058
Subject(s) - peptidoglycan , biology , cleavage (geology) , biochemistry , lysin , mutant , escherichia coli , glycan , enzyme , microbiology and biotechnology , sortase , bacterial cell structure , lysis , bacteria , glycoprotein , bacterial protein , paleontology , genetics , bacteriophage , fracture (geology) , gene
Summary Bacterial peptidoglycan ( PG or murein) is a single, large, covalently cross‐linked macromolecule and forms a mesh‐like sacculus that completely encases the cytoplasmic membrane. Hence, growth of a bacterial cell is intimately coupled to expansion of murein sacculus and requires cleavage of pre‐existing cross‐links for incorporation of new murein material. Although, conceptualized nearly five decades ago, the mechanism of such essential murein cleavage activity has not been studied so far. Here, we identify three new murein hydrolytic enzymes in E scherichia coli , two ( Spr and YdhO ) belonging to the NlpC / P 60 peptidase superfamily and the third ( YebA ) to the lysostaphin family of proteins that cleave peptide cross‐bridges between glycan chains. We show that these hydrolases are redundantly essential for bacterial growth and viability as a conditional mutant lacking all the three enzymes is unable to incorporate new murein and undergoes rapid lysis upon shift to restrictive conditions. Our results indicate the step of cross‐link cleavage as essential for enlargement of the murein sacculus, rendering it a novel target for development of antibacterial therapeutic agents.