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Antimicrobial Peptidomimetics Prevent the Development of Resistance against Gentamicin and Ciprofloxacin in Staphylococcus and Pseudomonas Bacteria.
Browne, Katrina; Kuppusamy, Rajesh; Walsh, William R; Black, David StC; Willcox, Mark D P; Kumar, Naresh; Chen, Renxun.
Afiliación
  • Browne K; School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia.
  • Kuppusamy R; Surgical and Orthopaedic Research Laboratories (SORL), Prince of Wales Clinical School, Prince of Wales Hospital, University of New South Wales (UNSW), Randwick 2031, Australia.
  • Walsh WR; School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia.
  • Black DS; School of Optometry and Vision Science, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia.
  • Willcox MDP; Surgical and Orthopaedic Research Laboratories (SORL), Prince of Wales Clinical School, Prince of Wales Hospital, University of New South Wales (UNSW), Randwick 2031, Australia.
  • Kumar N; School of Chemistry, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia.
  • Chen R; School of Optometry and Vision Science, University of New South Wales (UNSW) Sydney, Sydney 2052, Australia.
Int J Mol Sci ; 24(19)2023 Oct 06.
Article en En | MEDLINE | ID: mdl-37834415
Bacteria readily acquire resistance to traditional antibiotics, resulting in pan-resistant strains with no available treatment. Antimicrobial resistance is a global challenge and without the development of effective antimicrobials, the foundation of modern medicine is at risk. Combination therapies such as antibiotic-antibiotic and antibiotic-adjuvant combinations are strategies used to combat antibiotic resistance. Current research focuses on antimicrobial peptidomimetics as adjuvant compounds, due to their promising activity against antibiotic-resistant bacteria. Here, for the first time we demonstrate that antibiotic-peptidomimetic combinations mitigate the development of antibiotic resistance in Staphylococcus aureus and Pseudomonas aeruginosa. When ciprofloxacin and gentamicin were passaged individually at sub-inhibitory concentrations for 10 days, the minimum inhibitory concentrations (MICs) increased up to 32-fold and 128-fold for S. aureus and P. aeruginosa, respectively. In contrast, when antibiotics were passaged in combination with peptidomimetics (Melimine, Mel4, RK758), the MICs of both antibiotics and peptidomimetics remained constant, indicating these combinations were able to mitigate the development of antibiotic-resistance. Furthermore, antibiotic-peptidomimetic combinations demonstrated synergistic activity against both Gram-positive and Gram-negative bacteria, reducing the concentration needed for bactericidal activity. This has significant potential clinical applications-including preventing the spread of antibiotic-resistant strains in hospitals and communities, reviving ineffective antibiotics, and lowering the toxicity of antimicrobial chemotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peptidomiméticos / Antiinfecciosos Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peptidomiméticos / Antiinfecciosos Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza