Novel Iron-Chelator DIBI Inhibits Staphylococcus aureus Growth, Suppresses Experimental MRSA Infection in Mice and Enhances the Activities of Diverse Antibiotics in vitro

Frontiers in Microbiology
Maria Del Carmen ParquetBruce E Holbein

Abstract

DIBI, a purpose-designed hydroxypyridinone-containing iron-chelating antimicrobial polymer was studied for its anti-staphylococcal activities in vitro in comparison to deferiprone, the chemically related, small molecule hydroxypyridinone chelator. The sensitivities of 18 clinical isolates of Staphylococcus aureus from human, canine and bovine infections were determined. DIBI was strongly inhibitory to all isolates, displaying approximately 100-fold more inhibitory activity than deferiprone when compared on their molar iron-binding capacities. Sensitivity to DIBI was similar for both antibiotic-resistant and -sensitive isolates, including hospital- and community-acquired (United States 300) MRSA. DIBI inhibition was primarily bacteriostatic in nature at low concentration and was reversible by addition of Fe. DIBI also exhibited in vivo anti-infective activity in two distinct MRSA ATCC43300 infection and colonization models in mice. In a superficial skin wound infection model, topical application of DIBI provided a dose-dependent suppression of infection along with reduced wound inflammation. Intranasal DIBI reduced staphylococcal burden by >2 log in a MRSA nares carriage model. DIBI was also examined for its influence on antibio...Continue Reading

References

Apr 6, 2004·Current Opinion in Chemical Biology·Anne-Frances Miller
Jul 29, 2005·Antimicrobial Agents and Chemotherapy·Elisabeth KugelbergDiarmaid Hughes
Jun 15, 2007·Journal of Animal Science·P LacasseD Petitclerc
Aug 5, 2008·Biochimica Et Biophysica Acta·Eugene D Weinberg
Feb 5, 2009·Pediatric Research·George Y Liu
Apr 29, 2009·Journal of Korean Medical Science·Choon-Mee Kim, Sung-Heui Shin
Jul 15, 2009·Recent Patents on Anti-infective Drug Discovery·Mathieu BalloucheChristine Baysse
Apr 21, 2010·FEMS Microbiology Letters·Bruce E Holbein, Ramón Mira de Orduña
Jun 7, 2011·Annual Review of Microbiology·Neal D Hammer, Eric P Skaar
Nov 4, 2011·Seminars in Immunopathology·James E Cassat, Eric P Skaar
Nov 30, 2011·Microbes and Infection·Kathryn P Haley, Eric P Skaar
Feb 23, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Richard A Proctor
Aug 2, 2012·Antimicrobial Agents and Chemotherapy·Mitchell G ThompsonDaniel V Zurawski
Dec 3, 2013·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·G LuoA S Ibrahim
May 29, 2015·Clinical Microbiology Reviews·Steven Y C TongVance G Fowler
Jul 27, 2015·Experimental and Molecular Pathology·Melanie R Power CoombsDavid W Hoskin
Sep 20, 2016·Scientific Reports·Diego Chaves-MorenoDietmar H Pieper

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Citations

Apr 5, 2020·International Journal of Molecular Sciences·Marialaura MarchettiLuca Ronda
Oct 20, 2020·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Roger Gumbau-BrisaMatthias Bierenstiel
Dec 31, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alita R BurmeisterMichael E Hochberg
Jan 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cassidy ScottChristian Lehmann
Mar 19, 2021·FEMS Microbiology Reviews·Amber J BartonAndrew J Pollard
Apr 4, 2021·International Journal of Molecular Sciences·Víctor Vinuesa, Michael J McConnell
Jun 10, 2021·ACS Chemical Biology·Usama AbbasiJayachandran N Kizhakkedathu
Oct 8, 2020·Journal of Medicinal Chemistry·Xiaoying JiangYuanyuan Xie
Jul 9, 2020·ACS Applied Materials & Interfaces·Srinivas AbbinaJayachandran N Kizhakkedathu

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