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Novel Miniature Membrane Active Lipopeptidomimetics against Planktonic and Biofilm Embedded Methicillin-Resistant Staphylococcus aureus.
Joshi, Seema; Mumtaz, Sana; Singh, Jyotsna; Pasha, Santosh; Mukhopadhyay, Kasturi.
Afiliación
  • Joshi S; Antimicrobial Research Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. joshi.seema25@gmail.com.
  • Mumtaz S; Antimicrobial Research Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
  • Singh J; Antimicrobial Research Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
  • Pasha S; Peptide Research Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, New Delhi, 110007, India.
  • Mukhopadhyay K; Antimicrobial Research Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. kasturim@mail.jnu.ac.in.
Sci Rep ; 8(1): 1021, 2018 01 18.
Article en En | MEDLINE | ID: mdl-29348589
Escalating multidrug resistance and highly evolved virulence mechanisms have aggravated the clinical menace of methicillin-resistant Staphylococcus aureus (MRSA) infections. Towards development of economically viable staphylocidal agents here we report eight structurally novel tryptophan-arginine template based peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S-7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and good to potent activity against clinically relevant pathogens MRSA, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (MIC: 1.4-22.7 µg/mL). Mechanistically, the active peptidomimetics dissipated membrane potential and caused massive permeabilization on MRSA concomitant with loss of viability. Against stationary phase MRSA under nutrient-depleted conditions, active peptidomimetics S-7 and S-8 achieved > 6 log reduction in viability upon 24 h incubation while both S-7 (at 226 µg/mL) and S-8 (at 28 µg/mL) also destroyed 48 h mature MRSA biofilm causing significant decrease in viability (p < 0.05). Encouragingly, most active peptidomimetic S-8 maintained efficacy against MRSA in presence of serum/plasma while exhibiting no increase in MIC over 17 serial passages at sub-MIC concentrations implying resistance development to be less likely. Therefore, we envisage that the current template warrants further optimization towards the development of cell selective peptidomimetics for the treatment of device associated MRSA infections.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plancton / Biopelículas / Péptidos Catiónicos Antimicrobianos / Staphylococcus aureus Resistente a Meticilina / Lipopéptidos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plancton / Biopelículas / Péptidos Catiónicos Antimicrobianos / Staphylococcus aureus Resistente a Meticilina / Lipopéptidos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido