Dataset Information

Acetylome reveals the lysine acetylation modifications on outer membrane protein Aha1 in Aeromonas hydrophila regulate the porin permeability to multidrug antibiotics

ABSTRACT: Acetylome reveals the lysine acetylation modifications on outer membrane protein Aha1 in Aeromonas hydrophila regulate the porin permeability to multidrug antibiotics

ORGANISM(S): Aeromonas Hydrophila Subsp. Hydrophila Atcc 7966

SUBMITTER: Xiangmin Lin

PROVIDER: PXD028447 | iProX | Thu Apr 28 00:00:00 BST 2022

REPOSITORIES: iProX

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Publications

The Lysine Acetylation Modification in the Porin Aha1 of Aeromonas hydrophila Regulates the Uptake of Multidrug Antibiotics.

Zhang Lishan L Yao Zujie Z Tang Huamei H Song Qingli Q Song Huanhuan H Yao Jindong J Li Zhen Z Xie Xiaofang X Lin Yuexu Y Lin Xiangmin X

Molecular & cellular proteomics : MCP 20220521 9

Protein lysine acetylation (Kac) modification plays important roles in diverse physiological functions. However, there is little evidence on the role of Kac modification in bacterial antibiotic resistance. Here, we compared the differential expressions of whole-cell proteins and Kac peptides in oxytetracycline sensitive and oxytetracycline resistance (OXY<sup>R</sup>) strains of Aeromonas hydrophila using quantitative proteomics technologies. We observed a porin family protein Aha1 downregulated ...[more]

PMID: 35605723

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Project description:The emergence of multidrug resistant tuberculosis and the increasing level of resistance urges the search for alternative drugs in treatment. Several neuroleptics, like thioridazine, reveal activity against Mycobacterium tuberculosis. Thioridazine was even successfully applied in compassionate therapy of extensively drug resistant tuberculosis in patients when added to other second and third line antibiotics. The synergistic effects between thioridazine and other anti-tuberculosis drugs is usually assigned to the inhibition of efflux pumps by thioridazine. Using an unbiased proteomic approach, we set out to unravel the molecular mechanism of this potential new anti-tuberculosis component by examining the impact of continuous thioridazine exposure on the proteome of M. tuberculosis. We discovered that under the influence of thioridazine several proteins involved in the maintenance of the cell wall permeability barrier are differentially regulated, while none of the known mycobacterial efflux pumps was differentially regulated on the protein level. By assessing accumulation of fluorescent dyes in M. tuberculosis over time, we demonstrated that long-term drug exposure of M. tuberculosis indeed affected the mycobacterial cell envelope and increased the permeability towards both hydrophilic and hydrophobic compounds. Furthermore, we demonstrated that treatment of M. tuberculosis with thioridazine altered the composition of the plasma membrane. Thioridazine induced an increase in cell envelope permeability, and thereby the enhanced uptake of compounds, this could explain the previously reported synergistic effects between thioridazine and other anti-tuberculosis drugs. Although the hypothesis of higher intercellular drug concentrations by THZ has not changed in this study, the more exact knowledge on its mode of action is a major step forward. This new insight in the molecular mechanism of this anti-tuberculosis compound could facilitate further development of this class of drugs for application in drug therapy of multidrug resistant tuberculosis. In fact, the efficacy of many existing drugs could be improved significantly.

Dataset Information

Acetylome reveals the lysine acetylation modifications on outer membrane protein Aha1 in Aeromonas hydrophila regulate the porin permeability to multidrug antibiotics

Publications

The Lysine Acetylation Modification in the Porin Aha1 of Aeromonas hydrophila Regulates the Uptake of Multidrug Antibiotics.

Similar Datasets

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