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ClpP1P2 peptidase activity promotes biofilm formation in Pseudomonas aeruginosa
Author(s) -
Mawla Gina D.,
Hall Branwen M.,
CárcamoOyarce Gerardo,
Grant Robert A.,
Zhang Jia Jia,
Kardon Julia R.,
Ribbeck Katharina,
Sauer Robert T.,
Baker Tania A.
Publication year - 2021
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.14649
Subject(s) - proteolysis , biology , proteases , pseudomonas aeruginosa , biofilm , microbiology and biotechnology , cleavage (geology) , bacteria , pathogen , biochemistry , enzyme , genetics , paleontology , fracture (geology)
C aseino l ytic p roteases (Clp) are central to bacterial proteolysis and control cellular physiology and stress responses. They are composed of a double‐ring compartmentalized peptidase (ClpP) and a AAA+ unfoldase (ClpX or ClpA/ClpC). Unlike many bacteria, the opportunistic pathogen Pseudomonas aeruginosa contains two ClpP homologs: ClpP1 and ClpP2. The specific functions of these homologs, however, are largely elusive. Here, we report that the active form of PaClpP2 is a part of a heteromeric PaClpP1 7 P2 7 tetradecamer that is required for proper biofilm development. PaClpP1 14 and PaClpP1 7 P2 7 complexes exhibit distinct peptide cleavage specificities and interact differentially with P. aeruginosa ClpX and ClpA. Crystal structures reveal that PaClpP2 has non‐canonical features in its N‐ and C‐terminal regions that explain its poor interaction with unfoldases. However, experiments in vivo indicate that the PaClpP2 peptidase active site uniquely contributes to biofilm development. These data strongly suggest that the specificity of different classes of ClpP peptidase subunits contributes to the biological outcome of proteolysis. This specialized role of PaClpP2 highlights it as an attractive target for developing antimicrobial agents that interfere specifically with late‐stage P. aeruginosa development.