Mechanisms and clinical importance of bacteriophage resistance

Julia E Egido; Ana Rita Costa; Cristian Aparicio-Maldonado; Pieter-Jan Haas; Stan J J Brouns

doi:10.1093/femsre/fuab048

Mechanisms and clinical importance of bacteriophage resistance

FEMS Microbiol Rev. 2022 Feb 9;46(1):fuab048. doi: 10.1093/femsre/fuab048.

Authors

Julia E Egido¹, Ana Rita Costa^{2

3

4}, Cristian Aparicio-Maldonado^{2

3}, Pieter-Jan Haas¹, Stan J J Brouns^{2

3

4}

Affiliations

¹ Medical Microbiology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
² Department of Bionanoscience, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, Netherlands.
³ Kavli Institute of Nanoscience, van der Maasweg 9, 2629 HZ Delft, Netherlands.
⁴ Fagenbank, van der Maasweg 9, 2629 HZ Delft, Netherlands.

Abstract

We are in the midst of a golden age of uncovering defense systems against bacteriophages. Apart from the fundamental interest in these defense systems, and revolutionary applications that have been derived from them (e.g. CRISPR-Cas9 and restriction endonucleases), it is unknown how defense systems contribute to resistance formation against bacteriophages in clinical settings. Bacteriophages are now being reconsidered as therapeutic agents against bacterial infections due the emergence of multidrug resistance. However, bacteriophage resistance through defense systems and other means could hinder the development of successful phage-based therapies. Here, we review the current state of the field of bacteriophage defense, highlight the relevance of bacteriophage defense for potential clinical use of bacteriophages as therapeutic agents and suggest new directions of research.

Keywords: adaptive immunity; bacteria; defense; innate immunity; phage resistance; phage therapy.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Bacterial Infections*
Bacteriophages* / genetics
CRISPR-Cas Systems
Humans
Phage Therapy*