Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria.
TLDR
The antidiabetic drug metformin exhibits the potentiation effect on tetracycline antibiotics, particularly doxycycline and minocycline, against MDR S. aureus, E. coli, and S. enteritidis and boosts the immune response and alleviates the inflammatory responses in vitro.Abstract:
Highly persistent incidence of multidrug resistant (MDR) bacterial pathogens constitutes a global burden for public health. An alternative strategy to alleviate such a crisis is to identify promising compounds to restore antibiotics activity against MDR bacteria. It is reported that the antidiabetic drug metformin exhibits the potentiation effect on tetracycline antibiotics, particularly doxycycline and minocycline, against MDR S. aureus, E. faecalis, E. coli, and S. enteritidis. Mechanistic studies demonstrate that metformin promotes intracellular accumulation of doxycycline in tetracycline-resistant E. coli. In addition, metformin boosts the immune response and alleviates the inflammatory responses in vitro. Last, metformin fully restores the activity of doxycycline in three animal infection models. Collectively, these results reveal the potential of metformin as a novel tetracyclines adjuvant to circumvent MDR bacterial pathogens and to improve the treatment outcome of recalcitrant infections.read more
Citations
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Plant Natural Flavonoids Against Multidrug Resistant Pathogens.
Meirong Song,Ying Liu,Tingting Li,Xiaojia Liu,Zhihui Hao,Shuangyang Ding,Pharkphoom Panichayupakaranant,Kui Zhu,Jianzhong Shen +8 more
TL;DR: In this article, the potential of natural flavonoids from plants against multidrug resistant (MDR) bacteria, is demonstrated, and two compounds, α-mangostin (AMG) and isobavachalcone (IBC), are obtained.
Journal ArticleDOI
Metformin Targets Mitochondrial Electron Transport to Reduce Air Pollution-Induced Thrombosis
Saul Soberanes,Alexander V. Misharin,Amit Jairaman,Luisa Morales-Nebreda,Alexandra C. McQuattie-Pimentel,Takugo Cho,Robert B. Hamanaka,Angelo Y. Meliton,Paul A. Reyfman,James M. Walter,Ching I. Chen,Monica Chi,Stephen Chiu,Francisco J. Gonzalez-Gonzalez,Matthew Antalek,Hiam Abdala-Valencia,Sergio E. Chiarella,Kaitlyn A. Sun,Parker S. Woods,Andrew J. Ghio,Manu Jain,Harris Perlman,Karen M. Ridge,Richard I. Morimoto,Jacob I. Sznajder,William E. Balch,Sangeeta Bhorade,Ankit Bharat,Murali Prakriya,Navdeep S. Chandel,Gökhan M. Mutlu,Gökhan M. Mutlu,G. R. Scott Budinger +32 more
TL;DR: Targeted genetic deletion of electron transport or CRAC channels in alveolar macrophages in mice prevented particulate matter-induced acceleration of arterial thrombosis, suggesting metformin as a potential therapy to prevent some of the premature deaths attributable to air pollution exposure worldwide.
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Gut microbiome alterations in high-fat-diet-fed mice are associated with antibiotic tolerance.
Yuan Liu,Kangni Yang,Yuqian Jia,Jingru Shi,Ziwen Tong,Dan Fang,Bingqing Yang,Chengrui Su,Ruichao Li,Xia Xiao,Zhiqiang Wang +10 more
TL;DR: In this paper, the authors evaluated the efficacy of multiple clinically relevant bactericidal antibiotics in HFD-fed mice infected with methicillin-resistant Staphylococcus aureus (MRSA) or Escherichia coli.
Journal ArticleDOI
Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria.
TL;DR: In this article, the authors provide a brief overview of the co-evolution of antibiotic discovery and the development of bacterial resistance and uncover the art of repurposing non-antibiotic drugs as potential antibiotic adjuvants.
Journal ArticleDOI
Sublethal Levels of Antibiotics Promote Bacterial Persistence in Epithelial Cells.
TL;DR: It is demonstrated that extracellular bacteria show invasive behavior and survive in epithelial cells in both in vivo and in vitro models, to increase antibiotic tolerance and highlight the potential of host cells mediated antibiotic tolerance, which markedly compromises antibiotic efficacy and worsens the outcomes of infection.
References
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Performance standards for antimicrobial susceptibility testing
TL;DR: The supplemental information presented in this document is intended for use with the antimicrobial susceptibility testing procedures published in the following Clinical and Laboratory Standards Institute (CLSI)–approved standards.
Journal ArticleDOI
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
William C. Knowler,Elizabeth Barrett-Connor,Sarah E. Fowler,Richard F. Hamman,John M. Lachin,Elizabeth A. Walker,David M. Nathan +6 more
TL;DR: In this paper, the authors compared a lifestyle intervention with metformin to prevent or delay the development of Type 2 diabetes in nondiabetic individuals. And they found that the lifestyle intervention was significantly more effective than the medication.
Journal ArticleDOI
Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
Journal ArticleDOI
A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry
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Journal ArticleDOI
Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America
Helen W. Boucher,George H. Talbot,John S. Bradley,John S. Bradley,John E. Edwards,John E. Edwards,David N. Gilbert,Louis B. Rice,Louis B. Rice,Michael Scheld,Brad Spellberg,Brad Spellberg,John G. Bartlett +12 more
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