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An important role for periplasmic storage in Pseudomonas aeruginosa copper homeostasis revealed by a combined experimental and computational modeling study
Author(s) -
Parmar Jignesh H.,
Quintana Julia,
Ramírez David,
Laubenbacher Reinhard,
Argüello José M.,
Mendes Pedro
Publication year - 2018
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.14086
Subject(s) - periplasmic space , efflux , pseudomonas aeruginosa , copper , biology , mutant , atpase , bacteria , biochemistry , biophysics , microbiology and biotechnology , escherichia coli , chemistry , genetics , enzyme , gene , organic chemistry
Summary Biological systems require precise copper homeostasis enabling metallation of cuproproteins while preventing metal toxicity. In bacteria, sensing, transport, and storage molecules act in coordination to fulfill these roles. However, there is not yet a kinetic schema explaining the system integration. Here, we report a model emerging from experimental and computational approaches that describes the dynamics of copper distribution in Pseudomonas aeruginosa . Based on copper uptake experiments, a minimal kinetic model describes well the copper distribution in the wild‐type bacteria but is unable to explain the behavior of the mutant strain lacking CopA1, a key Cu + efflux ATPase. The model was expanded through an iterative hypothesis‐driven approach, arriving to a mechanism that considers the induction of compartmental pools and the parallel function of CopA and Cus efflux systems. Model simulations support the presence of a periplasmic copper storage with a crucial role under dyshomeostasis conditions in P. aeruginosa . Importantly, the model predicts not only the interplay of periplasmic and cytoplasmic pools but also the existence of a threshold in the concentration of external copper beyond which cells lose their ability to control copper levels.