Combination of gallium(iii) with acetate for combating antibiotic resistant Pseudomonas aeruginosa

Chemical Science
Yuchuan WangHongzhe Sun

Abstract

Gallium(iii) has been widely used as a diagnostic and therapeutic agent in clinics for the treatment of various diseases, in particular, Ga-based drugs have been exploited as antimicrobials to combat the crisis of antimicrobial resistance. The therapeutic properties of Ga(iii) are believed to be attributable to its chemical similarity to Fe(iii). However, the molecular mechanisms of action of gallium remain unclear. Herein, by integrating metalloproteomics with metabolomics and transcriptomics, we for the first time identified RpoB and RpoC, two subunits of RNA polymerase, as Ga-binding proteins in Pseudomonas aeruginosa. We show that Ga(iii) targets the essential transcription enzyme RNA polymerase to suppress RNA synthesis, resulting in reduced metabolic rates and energy utilization. Significantly, we show that exogenous supplementation of acetate could enhance the antimicrobial activity of Ga(iii), evidenced by the inhibited growth of persister cells and attenuated bacterial virulence. The effectiveness of co-therapy of Ga(iii) and acetate was further validated in mammalian cell and murine skin infection models, which is attributable to enhanced uptake of Ga(iii), and reduced TCA cycle flow and bacterial respiration. Our stu...Continue Reading

References

Oct 10, 2002·The Journal of Biological Chemistry·Maolin GuoPeter J Sadler
Feb 11, 2005·Chemical Reviews·Heinz G Floss, Tin-Wein Yu
Mar 17, 2007·The Journal of Clinical Investigation·Yukihiro KanekoPradeep K Singh
Feb 19, 2008·Trends in Microbiology·Sergei Borukhov, Evgeny Nudler
Oct 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ehud BaninEyal Banin
Jul 9, 2010·Analytical Chemistry·Karsten HillerGregory Stephanopoulos
May 13, 2011·Nature·Kyle R AllisonJames J Collins
Jul 13, 2011·Frontiers in Microbiology·Keith Poole
Apr 7, 2012·Nature Medicine·Taylor Sitarik Cohen, Alice Prince
Aug 1, 2012·Nucleic Acids Research·Magdalena N WojtasNicola G A Abrescia
May 15, 2013·Nature Reviews. Microbiology·Joseph A LemireRaymond J Turner
Jun 21, 2013·Science Translational Medicine·Jose Ruben Morones-RamirezJames J Collins
Sep 3, 2013·International Journal of Medical Microbiology : IJMM·Rodolfo García-ContrerasRafael Moreno-Sánchez
Sep 4, 2013·Journal of Infection and Public Health·B S NagobaR C Gandhi
Feb 18, 2014·BioFactors·Carlo BonchiEmanuela Frangipani
Apr 26, 2014·Future Microbiology·Fabrizia MinandriPaolo Visca
Feb 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yau-Tsz LaiHongzhe Sun
Apr 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael B HarbutFeng Wang
Jun 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael A LobritzJames J Collins
Jan 15, 2016·Microbiology and Molecular Biology Reviews : MMBR·Cong MaPeter J Lewis
May 8, 2016·Biochimica Et Biophysica Acta·Christopher R Chitambar
Jun 15, 2016·Journal of Microbiological Methods·Budoor AlqarniScott A Rice
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The UniProt Consortium
Feb 12, 2017·Frontiers in Cellular and Infection Microbiology·Sarah HijaziEmanuela Frangipani
May 23, 2017·Nature Reviews. Microbiology·Robert A FisherSophie Helaine
Aug 16, 2017·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Stefano DonatiHannes Link
Jan 3, 2018·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Noah Wald-DicklerBrad Spellberg
Feb 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yu-Bin SuXuan-Xian Peng
Feb 1, 2018·Nature Communications·Runming WangHongzhe Sun
Mar 10, 2018·Cell·Sylvain MeylanJames J Collins
Jul 24, 2018·Drug Discovery Today·Mohd W Azam, Asad U Khan
Sep 28, 2018·Science Translational Medicine·Christopher H GossPradeep K Singh

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Citations

Mar 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zeinab BreijyehRafik Karaman
Oct 7, 2020·Critical Reviews in Microbiology·Fazlurrahman KhanYoung-Mog Kim
Mar 25, 2020·Chemical Science·Angelo FreiMark A T Blaskovich
Oct 31, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Magdalena PiatekKevin Kavanagh
Apr 4, 2021·International Journal of Molecular Sciences·Víctor Vinuesa, Michael J McConnell
Oct 4, 2019·Journal of Medicinal Chemistry·Apurva PandeyEszter Boros
Jul 13, 2019·Inorganic Chemistry·Yuchuan WangHongzhe Sun
Sep 18, 2021·Chemical Society Reviews·Darren M GriffithHongzhe Sun

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Methods Mentioned

BETA
thermal shift
thermal
isothermal titration calorimetry
PCA
RNA-seq

Software Mentioned

IMAC
Ga

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