Resistance against two lytic phage variants attenuates virulence and antibiotic resistance in
biofilm
phage resistance
phage therapy
tradeoffs
virulence
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2023
2023
Historique:
received:
19
08
2023
accepted:
22
12
2023
medline:
2
2
2024
pubmed:
1
2
2024
entrez:
1
2
2024
Statut:
epublish
Résumé
Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance. In this work, we studied the Phage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the We show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy's evolutionary impact that may be exploited to generate robust therapy schemes.
Sections du résumé
Background
Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance.
Methods
In this work, we studied the
Results
Phage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the
Conclusions
We show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy's evolutionary impact that may be exploited to generate robust therapy schemes.
Identifiants
pubmed: 38298921
doi: 10.3389/fcimb.2023.1280265
pmc: PMC10828002
doi:
Substances chimiques
Virulence Factors
0
Anti-Bacterial Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1280265Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2024 García-Cruz, Rebollar-Juarez, Limones-Martinez, Santos-Lopez, Toya, Maeda, Ceapă, Blasco, Tomás, Díaz-Velásquez, Vaca-Paniagua, Díaz-Guerrero, Cazares, Cazares, Hernández-Durán, López-Jácome, Franco-Cendejas, Husain, Khan, Arshad, Morales-Espinosa, Fernández-Presas, Cadet, Wood and García-Contreras.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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