dc.contributor.author | Li, Qian | |
dc.contributor.author | Montalbán López, Manuel | |
dc.date.accessioned | 2021-02-22T12:13:07Z | |
dc.date.available | 2021-02-22T12:13:07Z | |
dc.date.issued | 2021-01-04 | |
dc.identifier.citation | Li, Q., Cebrián, R., Montalbán-López, M., Ren, H., Wu, W., & Kuipers, O. P. (2021). Outer-membrane-acting peptides and lipid II-targeting antibiotics cooperatively kill Gram-negative pathogens. Communications Biology, 4(1), 1-11. [DOI: 10.1038/s42003-020-01511-1] | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/66691 | |
dc.description.abstract | The development and dissemination of antibiotic-resistant bacterial pathogens is a growing
global threat to public health. Novel compounds and/or therapeutic strategies are required to
face the challenge posed, in particular, by Gram-negative bacteria. Here we assess the
combined effect of potent cell-wall synthesis inhibitors with either natural or synthetic
peptides that can act on the outer-membrane. Thus, several linear peptides, either alone or
combined with vancomycin or nisin, were tested against selected Gram-negative pathogens,
and the best one was improved by further engineering. Finally, peptide D-11 and vancomycin
displayed a potent antimicrobial activity at low μM concentrations against a panel of relevant
Gram-negative pathogens. This combination was highly active in biological fluids like blood,
but was non-hemolytic and non-toxic against cell lines. We conclude that vancomycin and D-
11 are safe at >50-fold their MICs. Based on the results obtained, and as a proof of concept for
the newly observed synergy, a Pseudomonas aeruginosa mouse infection model experiment
was also performed, showing a 4 log10 reduction of the pathogen after treatment with the
combination. This approach offers a potent alternative strategy to fight (drug-resistant)
Gram-negative pathogens in humans and mammals. | es_ES |
dc.description.sponsorship | China Scholarship Council
201306770012 | es_ES |
dc.description.sponsorship | European Union (EU) | es_ES |
dc.description.sponsorship | NWO-NACTAR program | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Research | es_ES |
dc.rights | Atribución 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.title | Outer-membrane-acting peptides and lipid II-targeting antibiotics cooperatively kill Gram-negative pathogens | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.1038/s42003-020-01511-1 | |
dc.type.hasVersion | VoR | es_ES |