@misc{10481/66691,
year = {2021},
month = {1},
url = {http://hdl.handle.net/10481/66691},
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.},
organization = {China Scholarship Council

201306770012},
organization = {European Union (EU)},
organization = {NWO-NACTAR program},
publisher = {Nature Research},
title = {Outer-membrane-acting peptides and lipid II-targeting antibiotics cooperatively kill Gram-negative pathogens},
doi = {10.1038/s42003-020-01511-1},
author = {Li, Qian and Montalbán López, Manuel},
}