Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Human Complement Inhibits Myophages against Pseudomonas aeruginosa

Julia E. Egido
ORCID logo ,
Simon O. Dekker
,
Catherine Toner-Bartelds
,
Cédric Lood
ORCID logo ,
Suzan H.M. Rooijakkers
,
Bart W. Bardoel
ORCID logo ,
Pieter-Jan Haas
*
Version 1 : Received: 29 September 2023 / Approved: 30 September 2023 / Online: 30 September 2023 (07:42:38 CEST)

A peer-reviewed article of this Preprint also exists.

Egido, J.E.; Dekker, S.O.; Toner-Bartelds, C.; Lood, C.; Rooijakkers, S.H.M.; Bardoel, B.W.; Haas, P.-J. Human Complement Inhibits Myophages against Pseudomonas aeruginosa. Viruses 2023, 15, 2211. Egido, J.E.; Dekker, S.O.; Toner-Bartelds, C.; Lood, C.; Rooijakkers, S.H.M.; Bardoel, B.W.; Haas, P.-J. Human Complement Inhibits Myophages against Pseudomonas aeruginosa. Viruses 2023, 15, 2211.

Abstract

Therapeutic phages are primarily chosen based on their in vitro bacteriolytic activity. Although anti-phage antibodies are known to inhibit phage infection, the influence of other immune system components is less well known. An important anti-bacterial and anti-viral innate immune system that may interact with phages is the complement system, a cascade of proteases that recognizes and targets invading microorganisms. In this study, we aimed to study the effects of serum components such as complement on the infectivity of different phages targeting Pseudomonas aeruginosa. We used a fluorescence-based assay to monitor the killing of P. aeruginosa by phages of different morphotypes in presence of human serum. Our results reveal that several myophages are inhibited by serum in a concentration-dependent way, while the activity of four podophages and one siphophage tested in this study is not affected by serum. By using specific nanobodies blocking different components of the complement cascade, we show that activation of the classical complement pathway is a driver of phage inhibition. To determine the mechanism of inhibition, we produced bioorthogonally labeled fluorescent phages to study their binding by means of microscopy and flow cytometry. We show that phage adsorption is hampered in presence of active complement. Our results indicate that interactions with complement may affect in vivo activity of therapeutically administered phages. A better understanding of this phenomenon is essential to optimize the design and application of therapeutic phage cocktails.

Keywords

phage therapy; phage inhibition; complement system; Pseudomonas aeruginosa; myophages

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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