ATH (ASX) Ann: Presentation of bioMUSE Data at the AAN Annual Meeting

Originally posted by pivalde: ↑

lwlinwei, thanks again. This is the new PBT2 paper
Open AccessArticle
Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria
by
David M. P. De Oliveira
^1,†,
Bernhard Keller
^1,†,
Andrew J. Hayes
² ,
Cheryl-Lynn Y. Ong
¹ ,
Nichaela Harbison-Price
¹,
Ibrahim M. El-Deeb
³,
Gen Li
¹ ,
Nadia Keller
¹,
Lisa Bohlmann
¹,
Stephan Brouwer
¹,
Andrew G. Turner
¹ ,
Amanda J. Cork
¹,
Thomas R. Jones
⁴ ,
David L. Paterson
⁵,
Alastair G. McEwan
¹,
Mark R. Davies
² ,
Christopher A. McDevitt
^2,‡,
Mark von Itzstein
^3,‡and
Mark J. Walker
^1,*,‡

¹
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
²
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia
³
Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia
⁴
School of Earth and Environmental Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
⁵
Australian Infectious Diseases Research Centre, UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4006, Australia
^*
Author to whom correspondence should be addressed.
^†
These authors contributed equally to this work.
^‡
Equal contribution as corresponding authors.
Academic Editor: Karl Hansford
Antibiotics2022,11(4), 449;https://doi.org/10.3390/antibiotics11040449
Received: 7 February 2022/Revised: 16 March 2022/Accepted: 22 March 2022/Published: 25 March 2022
(This article belongs to the Special IssueNontraditional Antibiotics—Challenges and Triumphs, 2nd Volume)
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Abstract
Gram-positive bacteria do not produce lipopolysaccharide as a cell wall component. As such, the polymyxin class of antibiotics, which exert bactericidal activity against Gram-negative pathogens, are ineffective against Gram-positive bacteria. The safe-for-human-use hydroxyquinoline analog ionophore PBT2 has been previously shown to break polymyxin resistance in Gram-negative bacteria, independent of the lipopolysaccharide modification pathways that confer polymyxin resistance. Here, in combination with zinc, PBT2 was shown to break intrinsic polymyxin resistance inStreptococcus pyogenes(Group AStreptococcus; GAS),Staphylococcus aureus(including methicillin-resistantS. aureus), and vancomycin-resistantEnterococcus faecium. Using the globally disseminated M1T1 GAS strain 5448 as a proof of principle model, colistin in the presence of PBT2 + zinc was shown to be bactericidal in activity. Any resistance that did arise imposed a substantial fitness cost. PBT2 + zinc dysregulated GAS metal ion homeostasis, notably decreasing the cellular manganese content. Using a murine model of wound infection, PBT2 in combination with zinc and colistin proved an efficacious treatment against streptococcal skin infection. These findings provide a foundation from which to investigate the utility of PBT2 and next-generation polymyxin antibiotics for the treatment of Gram-positive bacterial infections.View Full-Text
Keywords:antimicrobial resistance;polymyxins;PBT2;ionophores;Gram-positive bacteria
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P...How many more years do we have patent protection for PBT2 vs. antimicrobial resistance?

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MinRes jumps 5% as the company meets production guidance – depressed iron ore prices be damned

Red Hawk upgrades Blacksmith with DSO mineral resource at the Eagle Deposit

Nine's staff strike as Paris Olympic coverage begins

Nova locks in NASDAQ US market listing at a value of only US$3.3M as ASX gets quieter and quieter

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