TheStreptococcus pyogenesM protein is involved in phenotypic resistance to phage A25 infection in presence of human serum DOI Creative Commons
Lionel Schiavolin,

Jenny Steinmetz,

Gwenaëlle Botquin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 7, 2024

Abstract Streptococcus pyogenes is responsible for mild to life-threatening infections. Bacteriophages, or phages, and their virulence genes play a key role in the emergence expansion of epidemics. However, relatively little known about biology S. particularly biologically relevant environments. During infection, conceals from host immune system through binding human serum proteins. This evasion mediated by surface proteins, such as M protein which major determinant pyogenes. Here, we demonstrate that proteins also confer phenotypic resistance phage A25 infection impeding adsorption. We have found that, although not directly involved this inhibition both IgG albumin, especially absence bound fatty acids. These findings highlight importance studying phages within physiological context, specifically environmental conditions they will be used. Author summary The issues antimicrobial resurgence like recent cases invasive infections, are prompting scientific community use complementary therapy. Phages often characterized laboratory very different site. uses protect against system. Our data illustrate how environment modulates susceptibility . transiently protects M25 strain lytic A25. protective effect part protein, target current vaccines. new function highlights need characterize bacteria-phage interactions more context increase chances success

Language: Английский

Phage therapy DOI
Mikael Skurnik,

Sivan Alkalay‐Oren,

Maarten Boon

et al.

Nature Reviews Methods Primers, Journal Year: 2025, Volume and Issue: 5(1)

Published: Feb. 13, 2025

Citations

4
Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients DOI Creative Commons
Mireia Bernabéu-Gimeno,

Marco Pardo-Freire,

Benjamin K. Chan

et al.

Med, Journal Year: 2024, Volume and Issue: 5(9), P. 1096 - 1111.e6

Published: June 24, 2024

Language: Английский

Citations

14
The complement system: A key player in the host response to infections DOI Creative Commons
Archana Jayaraman, Sarah Walachowski, Markus Bosmann

et al.

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(11)

Published: Aug. 27, 2024

Abstract Infections are one of the most significant healthcare and economic burdens across world as underscored by recent coronavirus pandemic. Moreover, with increasing incidence antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions design effective treatment strategies. The complement system a key arsenal host defense response pathogens bridges both innate adaptive immunity. However, in contest between mechanisms, not always victorious. Pathogens have evolved several approaches, including co‐opting regulators evade complement‐mediated killing. Furthermore, deficiencies proteins, genetic therapeutic, can lead inefficient pathogen eradication, rendering more susceptible certain infections. On other hand, overwhelming infection provoke fulminant activation uncontrolled inflammation potentially fatal tissue organ damage. This review presents overview critical aspects complement‐pathogen during discusses perspectives on designing therapies mitigate dysfunction limit injury.

Language: Английский

Citations

5
The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo DOI Creative Commons
Arne Echterhof, Tejas Dharmaraj, Arya Khosravi

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(20)

Published: Oct. 22, 2024

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, factors that govern bacteriophage pharmacokinetics vivo remain poorly understood. Here, we have examined contribution neutrophils, most abundant phagocytes body, i.v. administered uninfected mice. A single dose LPS-5, a recently used human clinical trials drug-resistant Pseudomonas aeruginosa, was both immunocompetent BALB/c and neutropenic CD1 Phage concentrations were assessed peripheral blood spleen at 0.25, 1, 2, 4, 8, 12, 24 hours after administration by plaque assay qPCR. We observed phage clearance only minimally affected neutropenia. Indeed, half-lives phages mice 3.45 3.66 hours, respectively. These data suggest neutrophil-mediated phagocytosis not major determinant clearance. Conversely, substantial discrepancy circulating levels over time when measured qPCR versus assay, suggesting significant inactivation occurs time. indicate alternative factors, but inactivate phages.

Language: Английский

Citations

4
A Novel Bacteriophage Infecting Multi-Drug- and Extended-Drug-Resistant Pseudomonas aeruginosa Strains DOI Creative Commons
Guillermo Santamaría-Corral, Israel Pagán, John Jairo Aguilera-Correa

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(6), P. 523 - 523

Published: June 3, 2024

The prevalence of carbapenem-resistant P. aeruginosa has dramatically increased over the last decade, and antibiotics alone are not enough to eradicate infections caused by this opportunistic pathogen. Phage therapy is a fresh treatment that can be administered under compassionate use, particularly against chronic cases. However, it necessary thoroughly characterize virus before therapeutic application. Our work describes discovery novel sequenced bacteriophage, vB_PaeP-F1Pa, containing an integrase, performs phylogenetical analysis, its stability at physiological pH temperature, latent period (40 min), burst size (394 ± 166 particles per bacterial cell), demonstrates ability infect MDR XDR strains. Moreover, bacteriophage was able inhibit growth bacteria inside preformed biofilms. present study offers road map analyze essential areas for successful phage infections, shows integrase also show good in vitro results, indicating very important perform genomic analysis any clinical order prevent adverse effects patients.

Language: Английский

Citations

2
TheStreptococcus pyogenesM protein is involved in phenotypic resistance to phage A25 infection in presence of human serum DOI Creative Commons
Lionel Schiavolin,

Jenny Steinmetz,

Gwenaëlle Botquin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 7, 2024

Abstract Streptococcus pyogenes is responsible for mild to life-threatening infections. Bacteriophages, or phages, and their virulence genes play a key role in the emergence expansion of epidemics. However, relatively little known about biology S. particularly biologically relevant environments. During infection, conceals from host immune system through binding human serum proteins. This evasion mediated by surface proteins, such as M protein which major determinant pyogenes. Here, we demonstrate that proteins also confer phenotypic resistance phage A25 infection impeding adsorption. We have found that, although not directly involved this inhibition both IgG albumin, especially absence bound fatty acids. These findings highlight importance studying phages within physiological context, specifically environmental conditions they will be used. Author summary The issues antimicrobial resurgence like recent cases invasive infections, are prompting scientific community use complementary therapy. Phages often characterized laboratory very different site. uses protect against system. Our data illustrate how environment modulates susceptibility . transiently protects M25 strain lytic A25. protective effect part protein, target current vaccines. new function highlights need characterize bacteria-phage interactions more context increase chances success

Language: Английский

Citations

0