Functional diversification of two Lon homologs enhances stress adaptation in Pseudomonas aeruginosa
- 1Stockholm University
Abstract
The Lon protease is a highly conserved ATP-dependent protease that contributes to protein quality control and regulatory processes across all domains of life. The opportunistic pathogen Pseudomonas aeruginosa, along with other members of the Pseudomonadales, encodes AsrA (aminoglycoside-induced stress response ATP-dependent protease), a second LonA-type protease in addition to canonical Lon. Although AsrA is upregulated by aminoglycoside stress, its biochemical activity, substrate spectrum, and cellular functions have remained elusive. Here, we demonstrate that AsrA is a temperature- and antimicrobial stress-induced protease with specialized functions and partial redundancy with Lon. Quantitative proteomics revealed a distinct AsrA substrate profile, while comparative biochemical analyses showed that AsrA and Lon share a substantial number of substrates in vitro but differ in their degradation kinetics, indicating divergent substrate preferences. Among the proteins preferentially degraded by AsrA is the quorum-sensing anti-activator QslA, and we show that AsrA-dependent QslA degradation under tobramycin stress induces quorum-sensing gene expression. Together, our findings demonstrate how duplication of a conserved protease can generate specialized regulatory functions through differential expression and substrate preference, expanding the proteolytic network that enables bacterial adaptation to stress.
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BibTeX
@misc{kallazhi2026functional,
title = {{Functional diversification of two Lon homologs enhances stress adaptation in Pseudomonas aeruginosa}},
author = {A. Kallazhi and M. Louski and W. Bakri and E. N. Vlachos and U. Romling and K. Jonas},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749167},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749167v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Functional diversification of two Lon homologs enhances stress adaptation in Pseudomonas aeruginosa
AU - A. Kallazhi
AU - M. Louski
AU - W. Bakri
AU - E. N. Vlachos
AU - U. Romling
AU - K. Jonas
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749167
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749167v1
AB - The Lon protease is a highly conserved ATP-dependent protease that contributes to protein quality control and regulatory processes across all domains of life. The opportunistic pathogen Pseudomonas aeruginosa, along with other members of the Pseudomonadales, encodes AsrA (aminoglycoside-induced stress response ATP-dependent protease), a second LonA-type protease in addition to canonical Lon. Although AsrA is upregulated by aminoglycoside stress, its biochemical activity, substrate spectrum, and cellular functions have remained elusive. Here, we demonstrate that AsrA is a temperature- and antimicrobial stress-induced protease with specialized functions and partial redundancy with Lon. Quantitative proteomics revealed a distinct AsrA substrate profile, while comparative biochemical analyses showed that AsrA and Lon share a substantial number of substrates in vitro but differ in their degradation kinetics, indicating divergent substrate preferences. Among the proteins preferentially degraded by AsrA is the quorum-sensing anti-activator QslA, and we show that AsrA-dependent QslA degradation under tobramycin stress induces quorum-sensing gene expression. Together, our findings demonstrate how duplication of a conserved protease can generate specialized regulatory functions through differential expression and substrate preference, expanding the proteolytic network that enables bacterial adaptation to stress.
ER -