Quantitative Proteomics Reveals That the Protein Components of Outer Membrane Vesicles (OMVs) in <i>Aeromonas hydrophila</i> Play Protective Roles in Antibiotic Resistance

Li, Gang; Wang, Yuqian; Ramanathan, S.; Zhang, Lishan; Song, Huanhuan; Song, Qingli; Wang, Guibin; Lin, Xiangmin

doi:10.1021/acs.jproteome.2c00114

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…aeruginosa that plays an essential role in bacterial communication in response to population change, including the activation of many virulence-associated programs. − This molecule has also been recognized to induce outer membrane vesicle (OMV) production through specific interactions with the P. aeruginosa OM. − In particular, PQS intercalation into the OM induces membrane curvature formation, which is an essential early step in OMV production. , Considering the influences of OMVs in the competitiveness and pathogenicity of many gram-negative bacterial species, − PQS has the potential as a drug target for combating various infectious diseases.…”

Section: Resultsmentioning

confidence: 99%

Effect of Local Stress on Accurate Modeling of Bacterial Outer Membranes Using All-Atom Molecular Dynamics

Pirhadi

Vanegas

Mithila

et al. 2022

J. Chem. Theory Comput.

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Biological membranes are fundamental components of living organisms that play an undeniable role in their survival. Molecular dynamics (MD) serves as an essential computational tool for studying biomembranes on molecular and atomistic scales. The status quo of MD simulations of biomembranes studies a nanometer-sized membrane patch periodically extended under periodic boundary conditions (PBCs). In nature, membranes are usually composed of different lipids in their two layers (referred to as leaflets). This compositional asymmetry imposes a fixed ratio of lipid numbers between the two leaflets in a periodically constrained membrane, which needs to be set appropriately. The widely adopted methods of defining a leaflet lipid ratio suffer from the lack of control over the mechanical tension of each leaflet, which could significantly influence research findings. In this study, we investigate the role of membrane-building protocol and the resulting initial stress state on the interaction between small molecules and asymmetric membranes. We model the outer membrane of Pseudomonas aeruginosa bacteria using two different building protocols and probe their interactions with the Pseudomonas quinolone signal (PQS). Our results show that differential stress could shift the position of free energy minimum for the PQS molecule between the two leaflets of the asymmetric membrane. This work provides critical insights into the relationship between the initial per-leaflet tension and the spontaneous intercalation of PQS.

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Section: Resultsmentioning

confidence: 99%

Effect of Local Stress on Accurate Modeling of Bacterial Outer Membranes Using All-Atom Molecular Dynamics

Pirhadi

Vanegas

Mithila

et al. 2022

J. Chem. Theory Comput.

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“…35,36 Additionally, EVs are being investigated as potential targets for new antimicrobial therapies, as they may play a key role in the development of antibiotic resistance. 37 EVs can also be obtained from plants. 38 Plant EVs have been detected in various plant species, including Arabidopsis, corn, and rice.…”

Section: Source Of Evsmentioning

confidence: 99%

“…35,36 Additionally, EVs are being investigated as potential targets for new antimicrobial therapies, as they may play a key role in the development of antibiotic resistance. 37 function in bacterial physiology and pathogenesis, and further research is needed to fully understand their roles in these processes. EVs can also be obtained from plants.…”

Section: Source Of Evsmentioning

confidence: 99%

“…EVs are also secreted by bacteria, containing various biomolecules such as lipids, proteins, and nucleic acids, and are thought to play important roles in intercellular communication and signaling . Recent studies have suggested that EVs may be involved in the pathogenesis of several bacterial infections, including those caused by Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa . , Additionally, EVs are being investigated as potential targets for new antimicrobial therapies, as they may play a key role in the development of antibiotic resistance . Despite these advances, however, much remains unknown about the precise mechanisms by which EVs function in bacterial physiology and pathogenesis, and further research is needed to fully understand their roles in these processes.…”

Section: Origin and Function Of Evsmentioning

confidence: 99%

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Milk Extracellular Vesicles: Natural Nanoparticles for Enhancing Oral Drug Delivery against Bacterial Infections

Dai,

Xu,

et al. 2024

ACS Biomater. Sci. Eng.

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Oral drug delivery is typically preferred as a therapeutic intervention due to the complexities and expenses associated with intravenous administration. However, some drugs are poorly absorbed orally, requiring intravenous administration to bypass the gastrointestinal tract and deliver the drug directly into the bloodstream. Thus, there is an urgent need to develop novel drug delivery platforms to overcome the challenges of oral drug delivery with low solubility, low permeability, oral degradation, and low bioavailability. Advances in extracellular vesicles (EVs) as natural carriers have provided emerging approaches to improve potential therapeutic applications. Milk not only contains traditional nutrients but is also rich in EVs. In this Review, we focus mainly on the purification of milk EVs (mEVs), their safety, and the advantages of mEV-based drug carriers in combatting intestinal infections. Additionally, we summarize several advantages of mEVs over conventional synthetic carriers, such as low immunogenicity, high biocompatibility, and the ability to transfer bioactive molecules between cells. Considering the unmet gaps of mEVs in clinical translation, it is essential to review the cargo loading into mEVs and future perspectives for their use as natural drug carriers for oral delivery. This overview of mEV-based drug carriers for oral delivery sheds light on alternative approaches to treat clinical infections associated with intestinal pathogens and the development of novel oral delivery systems.

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“…Tetracyclines work by binding specifically to the 30 S ribosome subunit of bacteria and interfering with the binding of aminoacyl-tRNA, which blocks bacterial protein translation and synthesis to inhibit bacterial growth. , A line of evidence has indicated that four drug-resistance mechanisms exist in tetracycline-resistant bacteria. They include the blocking of tetracycline-binding sites through ribosome protection proteins, − the reduction of membrane permeability to prevent tetracycline from entering the cell, − the inactivation of the tetracycline’s active site by enzymes, and the activation of efflux transporters to export the accumulating tetracycline out of the cells . These findings advance our understanding of tetracycline resistance, but our comprehension of tetracycline resistance is incomplete.…”

mentioning

confidence: 99%

Elevated Membrane Potential as a Tetracycline Resistance Mechanism in Escherichia coli

Kuang,

Xiang,

Zeng

et al. 2024

ACS Infect. Dis.

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The metabolic environment is responsible for antibiotic resistance, which highlights the way in which the antibiotic resistance mechanism works. Here, GC-MS-based metabolomics with iTRAQ-based proteomics was used to characterize a metabolic state in tetracycline-resistant Escherichia coli K12 (E. coli-R TET ) compared with tetracycline-sensitive E. coli K12. The repressed pyruvate cycle against the elevation of the proton motive force (PMF) and ATP constructed the most characteristic feature as a consequence of tetracycline resistance. To understand the role of the elevated PMF in tetracycline resistance, PMF inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and the pH gradient were used to investigate how the elevation influences bacterial viability and intracellular antibiotic concentration. A strong synergy was detected between CCCP and tetracycline to the viability, which was consistent with increasing intracellular drug and decreasing external pH. Furthermore, E. coli-R TET and E. coli-R GEN with high and low PMF concentrations were susceptible to gentamicin and tetracycline, respectively. The elevated PMF in E. coli-R TET was attributed to the activation of other metabolic pathways, except for the pyruvate cycle, including a malate−oxaloacetate−phosphoenolpyruvate−pyruvate−malate cycle. These results not only revealed a PMF-dependent mechanism for tetracycline resistance but also provided a solution to tetracycline-resistant pathogens by aminoglycosides and aminoglycosideresistant bacteria by tetracyclines.

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Quantitative Proteomics Reveals That the Protein Components of Outer Membrane Vesicles (OMVs) in Aeromonas hydrophila Play Protective Roles in Antibiotic Resistance

Cited by 8 publications

References 44 publications

Effect of Local Stress on Accurate Modeling of Bacterial Outer Membranes Using All-Atom Molecular Dynamics

Effect of Local Stress on Accurate Modeling of Bacterial Outer Membranes Using All-Atom Molecular Dynamics

Milk Extracellular Vesicles: Natural Nanoparticles for Enhancing Oral Drug Delivery against Bacterial Infections

Elevated Membrane Potential as a Tetracycline Resistance Mechanism in Escherichia coli

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