Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.

The emergence and rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to the global healthcare. There is an urgent need for new antibacterial substances or new treatment strategies to deal with the infections by MDR bacterial pathogens, especially the Gram-negative pathogens. I...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yushan Xia, Rubén Cebrián, Congjuan Xu, Anne de Jong, Weihui Wu, Oscar P Kuipers
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dad67f8297b1411196e95ff6b8347791
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dad67f8297b1411196e95ff6b8347791
record_format	dspace
spelling	oai:doaj.org-article:dad67f8297b1411196e95ff6b83477912021-12-02T20:00:13ZElucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.1553-73661553-737410.1371/journal.ppat.1009909https://doaj.org/article/dad67f8297b1411196e95ff6b83477912021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009909https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The emergence and rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to the global healthcare. There is an urgent need for new antibacterial substances or new treatment strategies to deal with the infections by MDR bacterial pathogens, especially the Gram-negative pathogens. In this study, we show that a number of synthetic cationic peptides display strong synergistic antimicrobial effects with multiple antibiotics against the Gram-negative pathogen Pseudomonas aeruginosa. We found that an all-D amino acid containing peptide called D-11 increases membrane permeability by attaching to LPS and membrane phospholipids, thereby facilitating the uptake of antibiotics. Subsequently, the peptide can dissipate the proton motive force (PMF) (reducing ATP production and inhibiting the activity of efflux pumps), impairs the respiration chain, promotes the production of reactive oxygen species (ROS) in bacterial cells and induces intracellular antibiotics accumulation, ultimately resulting in cell death. By using a P. aeruginosa abscess infection model, we demonstrate enhanced therapeutic efficacies of the combination of D-11 with various antibiotics. In addition, we found that the combination of D-11 and azithromycin enhanced the inhibition of biofilm formation and the elimination of established biofilms. Our study provides a realistic treatment option for combining close-to-nature synthetic peptide adjuvants with existing antibiotics to combat infections caused by P. aeruginosa.Yushan XiaRubén CebriánCongjuan XuAnne de JongWeihui WuOscar P KuipersPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009909 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Yushan Xia Rubén Cebrián Congjuan Xu Anne de Jong Weihui Wu Oscar P Kuipers Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.
description	The emergence and rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to the global healthcare. There is an urgent need for new antibacterial substances or new treatment strategies to deal with the infections by MDR bacterial pathogens, especially the Gram-negative pathogens. In this study, we show that a number of synthetic cationic peptides display strong synergistic antimicrobial effects with multiple antibiotics against the Gram-negative pathogen Pseudomonas aeruginosa. We found that an all-D amino acid containing peptide called D-11 increases membrane permeability by attaching to LPS and membrane phospholipids, thereby facilitating the uptake of antibiotics. Subsequently, the peptide can dissipate the proton motive force (PMF) (reducing ATP production and inhibiting the activity of efflux pumps), impairs the respiration chain, promotes the production of reactive oxygen species (ROS) in bacterial cells and induces intracellular antibiotics accumulation, ultimately resulting in cell death. By using a P. aeruginosa abscess infection model, we demonstrate enhanced therapeutic efficacies of the combination of D-11 with various antibiotics. In addition, we found that the combination of D-11 and azithromycin enhanced the inhibition of biofilm formation and the elimination of established biofilms. Our study provides a realistic treatment option for combining close-to-nature synthetic peptide adjuvants with existing antibiotics to combat infections caused by P. aeruginosa.
format	article
author	Yushan Xia Rubén Cebrián Congjuan Xu Anne de Jong Weihui Wu Oscar P Kuipers
author_facet	Yushan Xia Rubén Cebrián Congjuan Xu Anne de Jong Weihui Wu Oscar P Kuipers
author_sort	Yushan Xia
title	Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.
title_short	Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.
title_full	Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.
title_fullStr	Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.
title_full_unstemmed	Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.
title_sort	elucidating the mechanism by which synthetic helper peptides sensitize pseudomonas aeruginosa to multiple antibiotics.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/dad67f8297b1411196e95ff6b8347791
work_keys_str_mv	AT yushanxia elucidatingthemechanismbywhichsynthetichelperpeptidessensitizepseudomonasaeruginosatomultipleantibiotics AT rubencebrian elucidatingthemechanismbywhichsynthetichelperpeptidessensitizepseudomonasaeruginosatomultipleantibiotics AT congjuanxu elucidatingthemechanismbywhichsynthetichelperpeptidessensitizepseudomonasaeruginosatomultipleantibiotics AT annedejong elucidatingthemechanismbywhichsynthetichelperpeptidessensitizepseudomonasaeruginosatomultipleantibiotics AT weihuiwu elucidatingthemechanismbywhichsynthetichelperpeptidessensitizepseudomonasaeruginosatomultipleantibiotics AT oscarpkuipers elucidatingthemechanismbywhichsynthetichelperpeptidessensitizepseudomonasaeruginosatomultipleantibiotics
_version_	1718375751583006720

Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics.

Ejemplares similares