Directed evolution of phages in biofilms enhances Pseudomonas aeruginosa control through improved lipopolysaccharide recognition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143788" target="_blank" >RIV/00216224:14740/25:00143788 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-025-65014-5" target="_blank" >https://www.nature.com/articles/s41467-025-65014-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-025-65014-5" target="_blank" >10.1038/s41467-025-65014-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Directed evolution of phages in biofilms enhances Pseudomonas aeruginosa control through improved lipopolysaccharide recognition

Popis výsledku v původním jazyce

Pseudomonas aeruginosa is a leading cause of chronic lung infections in cystic fibrosis (CF) patients. While bacteriophages hold potential as a treatment for antibiotic-resistant infections, the complex structure and heterogeneity of P. aeruginosa biofilms pose significant challenges to phage therapy. In this study, we investigate the adaptive evolution of the Pbunavirus phage PE1 to biofilms formed by a CF-derived P. aeruginosa isolate. Our findings reveal that biofilm-adapted PE1 mutants exhibit enhanced efficacy in controlling biofilms in vitro under conditions mimicking the CF lung environment. This improvement is attributed to the mutants' increased ability to recognize the diverse populations within the biofilm. Using a combination of cryo-EM, lipopolysaccharide (LPS) profiling, and adsorption assays, we demonstrate that mutations in tail fiber and baseplate genes of the phage improve adsorption and enable recognition of truncated LPS variants. This study highlights the critical role of biofilm heterogeneity in limiting phage effectiveness, identifies mechanisms to overcome this barrier, and pinpoints specific genomic targets for engineering phages tailored for therapeutic applications in CF patients.

Název v anglickém jazyce

Directed evolution of phages in biofilms enhances Pseudomonas aeruginosa control through improved lipopolysaccharide recognition

Popis výsledku anglicky

Pseudomonas aeruginosa is a leading cause of chronic lung infections in cystic fibrosis (CF) patients. While bacteriophages hold potential as a treatment for antibiotic-resistant infections, the complex structure and heterogeneity of P. aeruginosa biofilms pose significant challenges to phage therapy. In this study, we investigate the adaptive evolution of the Pbunavirus phage PE1 to biofilms formed by a CF-derived P. aeruginosa isolate. Our findings reveal that biofilm-adapted PE1 mutants exhibit enhanced efficacy in controlling biofilms in vitro under conditions mimicking the CF lung environment. This improvement is attributed to the mutants' increased ability to recognize the diverse populations within the biofilm. Using a combination of cryo-EM, lipopolysaccharide (LPS) profiling, and adsorption assays, we demonstrate that mutations in tail fiber and baseplate genes of the phage improve adsorption and enable recognition of truncated LPS variants. This study highlights the critical role of biofilm heterogeneity in limiting phage effectiveness, identifies mechanisms to overcome this barrier, and pinpoints specific genomic targets for engineering phages tailored for therapeutic applications in CF patients.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

<a href="/cs/project/EH23_015%2F0008175" target="_blank" >EH23_015/0008175: Inovace České infrastruktury pro integrativní strukturní biologii</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

15

Strana od-do

1-15

Kód UT WoS článku

001620530800023

EID výsledku v databázi Scopus

2-s2.0-105022522130