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Bacterial susceptibility and resistance to modelin-5

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  • معلومة اضافية
    • بيانات النشر:
      Royal Society of Chemistry (RSC)
    • الموضوع:
      2023
    • Collection:
      University of Central Lancashire: CLOK - Central Lancashire Online Knowledge
    • نبذة مختصرة :
      Modelin-5 (M5-NH2) killed Pseudomonas aeruginosa with a minimum lethal concentration (MLC) of 5.86 μM and strongly bound its cytoplasmic membrane (CM) with a Kd of 23.5 μM. The peptide adopted high levels of amphiphilic α-helical structure (75.0%) and penetrated the CM hydrophobic core (8.0 mN m−1). This insertion destabilised CM structure via increased lipid packing and decreased fluidity (ΔGmix < 0), which promoted high levels of lysis (84.1%) and P. aeruginosa cell death. M5-NH2 showed a very strong affinity (Kd = 3.5 μM) and very high levels of amphiphilic α-helical structure with cardiolipin membranes (96.0%,) which primarily drove the peptide's membranolytic action against P. aeruginosa. In contrast, M5-NH2 killed Staphylococcus aureus with an MLC of 147.6 μM and weakly bound its CM with a Kd of 117.6 μM, The peptide adopted low levels of amphiphilic α-helical structure (35.0%) and only penetrated the upper regions of the CM (3.3 mN m−1). This insertion stabilised CM structure via decreased lipid packing and increased fluidity (ΔGmix > 0) and promoted only low levels of lysis (24.3%). The insertion and lysis of the S. aureus CM by M5-NH2 showed a strong negative correlation with its lysyl phosphatidylglycerol (Lys-PG) content (R2 > 0.98). In combination, these data suggested that Lys-PG mediated mechanisms inhibited the membranolytic action of M5-NH2 against S. aureus, thereby rendering the organism resistant to the peptide. These results are discussed in relation to structure/function relationships of M5-NH2 and CM lipids that underpin bacterial susceptibility and resistance to the peptide.
    • File Description:
      application/pdf
    • Relation:
      https://clok.uclan.ac.uk/49405/1/d3sm01007d.pdf; Dennison, Sarah R. orcid iconorcid:0000-0003-4863-9607 , Morton, Leslie Hugh Glyn, Badiani, Kamal, Harris, Frederick and Phoenix, David A. (2023) Bacterial susceptibility and resistance to modelin-5. Soft Matter . ISSN 1744-683X
    • الرقم المعرف:
      10.1039/D3SM01007D
    • Rights:
      cc_by_4
    • الرقم المعرف:
      edsbas.959195D7