Biology subjects

Dementin, S.

Publications and source records attributed to Dementin, S..

3 recordsLinked to original sources

bioRxiv2026

Conserved Functional Traits of the Atc Protein System

The Atc protein system (AtcJ, AtcA, AtcB and AtcC) plays a major role in cold adaptation in Shewanella oneidensis. AtcJ, a J-domain protein, interacts with the DnaK chaperone and binds AtcC through a conserved C-terminal PX7W motif in which Trp is crucial. Overproduced AtcB inhibits RNA polymerase, while the AtcJ-AtcC complex recruits DnaK to modulate this inhibition. This study investigates the conservation of these functional traits across divergent bacteria. We characterized several non-canonical Atc systems and demonstrated that the core interaction network remains functionally preserved despite remarkable variability in the AtcJ C-terminal motif, ranging from intact PX7W to degenerate or absent forms, but also in the size of AtcC. Phylogenetic analysis revealed vertical inheritance and co-evolution with host transcriptional machinery. AtcB, AtcC, and AtcJ exhibit strong phylogenetic congruence with the species tree, while AtcA shows greater evolutionary flexibility. The system is enriched in aquatic and psychrophilic lineages but absent in thermophiles. Conditional toxicity assays revealed that AtcB-RNAP interaction depends on specific structural determinants, with DnaK recruitment alleviating toxicity. These findings support a unified molecular mechanism coupling chaperone activity to transcriptional regulation under environmental stress, suggesting that the Atc system represents an ancient and adaptable regulatory module in bacteria.

microbiology↗

bioRxiv2025

Subtle variations in a client protein determine bacterial Hsp90 dependence

Chaperones ensure protein homeostasis and are conserved across species. The ATP-dependent chaperone Hsp90 is present from bacteria to eukaryotes, where it stabilizes and activates a wide range of substrate proteins called clients. However, what determines whether a protein depends on Hsp90 remains an open question. Here, we focused on the bacterial chaperone Hsp90 and its obligate client TilS (referred to as TilSSo) in the bacterium Shewanella oneidensis. Although Hsp90 is indispensable in S. oneidensis under heat stress by protecting the essential protein TilSSo from degradation by the protease HslUV, Hsp90 is dispensable in Escherichia coli, suggesting that E. coli TilS (TilSEc) is Hsp90 independent. We therefore compared the TilS orthologs with respect to in vitro stability, in vivo degradation, and interaction with Hsp90 to identify the determinants of the Hsp90 dependence. We found that in contrast to TilSSo, TilSEc was more stable, was not degraded by protease in the absence of Hsp90, and did not interact with Hsp90, indicating that TilSEc is not a client of Hsp90. Chimeras between TilSSo and TilSEc as well as directed mutagenesis revealed a region of TilSSo that is key for protease degradation and Hsp90 protection. Consistent with these results, the growth of S. oneidensis producing TilSEc was no longer dependent on Hsp90 under heat stress. Conversely, Hsp90 became essential for the growth of E. coli that produced TilSSo instead of TilSEc. Taken together, these results provide new insights into the mechanism of client protection by Hsp90 and the interplay between chaperones and proteases.

microbiology↗

bioRxiv2025

Bacterial Hsp90 promotes virulence factor production through maintenance of NRPS megaenzymes

Pathogenic bacteria produce virulence factors critical to host infection. Here, we demonstrate the crucial role of the bacterial Hsp90 chaperone in the production of two major virulence factors, the colibactin genotoxin in Escherichia coli and the pyoverdine siderophore in Pseudomonas aeruginosa. Colibactin, a hybrid polyketide/non-ribosomal peptide (PK-NRP), and pyoverdine, a non-ribosomal peptide (NRP), are metabolites produced by complex biosynthetic pathways involving large cytoplasmic enzymes called megasynthases. Using comparative proteomics, we found that megasynthase abundance was markedly reduced in hsp90 deletion mutants of E. coli and P. aeruginosa compared to wild-type strains. This reduction was independent of transcriptional or translational regulation. We further revealed an interplay between Hsp90 and the HslUV protease in controlling megasynthase levels. Remarkably, we found that Hsp90 stabilizes additional NRP and PK-NRP megasynthases, suggesting a general role for Hsp90 as a chaperone of these enzymes. These findings open new avenues for enhancing the biosynthesis of complex metabolites for biotechnological applications through proteostasis modulation, and may also have implications for combating bacterial infections.

microbiology↗