Cargando…
Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii In Vitro and Ex Vivo
Synergistic effects of phages in combination with antibiotics have received increasing attention. In this present study, we isolated a new phage pB3074 against clinically isolated multidrug-resistant Acinetobacter baumannii. Phage pB3074 combined with cell wall-targeting antibiotics could produce sy...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10434185/ https://www.ncbi.nlm.nih.gov/pubmed/37260382 http://dx.doi.org/10.1128/spectrum.00341-23 |
_version_ | 1785091827600195584 |
---|---|
author | Luo, Jun Xie, Libo Yang, Min Liu, Min Li, Qianyuan Wang, Peng Fan, Jinhong Jin, Jing Luo, Chunhua |
author_facet | Luo, Jun Xie, Libo Yang, Min Liu, Min Li, Qianyuan Wang, Peng Fan, Jinhong Jin, Jing Luo, Chunhua |
author_sort | Luo, Jun |
collection | PubMed |
description | Synergistic effects of phages in combination with antibiotics have received increasing attention. In this present study, we isolated a new phage pB3074 against clinically isolated multidrug-resistant Acinetobacter baumannii. Phage pB3074 combined with cell wall-targeting antibiotics could produce synergistic antibacterial effect in vitro bactericidal activities. Further research indicates that the bacteriophage dose is critical to synergistic antimicrobial effect of phage and antibiotic combination. Cefotaxime and meropenem were selected as the representative cell wall-targeting antibiotics for further synergistic antibacterial study. Results illustrated that phage pB3074 and cefotaxime or meropenem combination was very effective for the removal of mature biofilm and inhibition of biofilm formation. In a pig skin explant model, results also showed that phage pB3074 and cefotaxime or meropenem combination was very effective for the treatment of wound infection ex vivo. Subsequent studies showed that some extent recovery of drug sensitivity to cell wall-targeting antibiotics might be vital mechanism of synergistic antibacterial effect between bacteriophage pB3074 and these antibiotics. The existence of antibiotics could promote phage adsorption and proliferation, which might also be potential mechanism for synergistic antibacterial activities and have been observed in cefotaxime and meropenem application. In summary, results in the current study demonstrated that phage pB3074 has the potential to be developed as an antibacterial agent and combined application of phages and antibiotics might be a new choice for the treatment of current multidrug-resistant bacterial infections. IMPORTANCE Combined application of phages and antibiotics cannot only effectively inhibit the appearance of phage-resistant bacteria, but also reduce the effective use concentration of antibiotics, and even make some bacteria regain sensitivity to some resistant antibiotics. Therefore, phage-antibiotic combination (PAC) could improve the antibacterial activity of individual drug, providing a new choice for clinical treatment of multidrug-resistant bacterial infections. |
format | Online Article Text |
id | pubmed-10434185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-104341852023-08-18 Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii In Vitro and Ex Vivo Luo, Jun Xie, Libo Yang, Min Liu, Min Li, Qianyuan Wang, Peng Fan, Jinhong Jin, Jing Luo, Chunhua Microbiol Spectr Research Article Synergistic effects of phages in combination with antibiotics have received increasing attention. In this present study, we isolated a new phage pB3074 against clinically isolated multidrug-resistant Acinetobacter baumannii. Phage pB3074 combined with cell wall-targeting antibiotics could produce synergistic antibacterial effect in vitro bactericidal activities. Further research indicates that the bacteriophage dose is critical to synergistic antimicrobial effect of phage and antibiotic combination. Cefotaxime and meropenem were selected as the representative cell wall-targeting antibiotics for further synergistic antibacterial study. Results illustrated that phage pB3074 and cefotaxime or meropenem combination was very effective for the removal of mature biofilm and inhibition of biofilm formation. In a pig skin explant model, results also showed that phage pB3074 and cefotaxime or meropenem combination was very effective for the treatment of wound infection ex vivo. Subsequent studies showed that some extent recovery of drug sensitivity to cell wall-targeting antibiotics might be vital mechanism of synergistic antibacterial effect between bacteriophage pB3074 and these antibiotics. The existence of antibiotics could promote phage adsorption and proliferation, which might also be potential mechanism for synergistic antibacterial activities and have been observed in cefotaxime and meropenem application. In summary, results in the current study demonstrated that phage pB3074 has the potential to be developed as an antibacterial agent and combined application of phages and antibiotics might be a new choice for the treatment of current multidrug-resistant bacterial infections. IMPORTANCE Combined application of phages and antibiotics cannot only effectively inhibit the appearance of phage-resistant bacteria, but also reduce the effective use concentration of antibiotics, and even make some bacteria regain sensitivity to some resistant antibiotics. Therefore, phage-antibiotic combination (PAC) could improve the antibacterial activity of individual drug, providing a new choice for clinical treatment of multidrug-resistant bacterial infections. American Society for Microbiology 2023-06-01 /pmc/articles/PMC10434185/ /pubmed/37260382 http://dx.doi.org/10.1128/spectrum.00341-23 Text en Copyright © 2023 Luo et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Luo, Jun Xie, Libo Yang, Min Liu, Min Li, Qianyuan Wang, Peng Fan, Jinhong Jin, Jing Luo, Chunhua Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii In Vitro and Ex Vivo |
title | Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii
In Vitro and Ex Vivo |
title_full | Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii
In Vitro and Ex Vivo |
title_fullStr | Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii
In Vitro and Ex Vivo |
title_full_unstemmed | Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii
In Vitro and Ex Vivo |
title_short | Synergistic Antibacterial Effect of Phage pB3074 in Combination with Antibiotics Targeting Cell Wall against Multidrug-Resistant Acinetobacter baumannii
In Vitro and Ex Vivo |
title_sort | synergistic antibacterial effect of phage pb3074 in combination with antibiotics targeting cell wall against multidrug-resistant acinetobacter baumannii
in vitro and ex vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10434185/ https://www.ncbi.nlm.nih.gov/pubmed/37260382 http://dx.doi.org/10.1128/spectrum.00341-23 |
work_keys_str_mv | AT luojun synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT xielibo synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT yangmin synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT liumin synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT liqianyuan synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT wangpeng synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT fanjinhong synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT jinjing synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo AT luochunhua synergisticantibacterialeffectofphagepb3074incombinationwithantibioticstargetingcellwallagainstmultidrugresistantacinetobacterbaumanniiinvitroandexvivo |