is a bacterial pathogen that is a major cause of lung infections in cystic fibrosis (CF) and other patients. Isolates of from CF patients commonly carry filamentous phages (Pf phages), which constitute a family of temperate phages known to be related to biofilm production and antibiotic sequestration. In this study, we identified 12 new Pf phage genomes in a collection of clinical isolates of from CF patients. Study of the anti-phage defense systems in the bacterial isolates revealed the presence of 89 such systems, of which eight were encoded in the Pf phage genomes. Finally, although a weak relation between resistance to phage infection and the number of anti-phage defense systems was detected, it was observed that the phage resistance was related to the presence of Pf phages and the anti-phage defense systems encoded in these phages.IMPORTANCEBacteria harbor a wide range of defense mechanisms to avoid phage infections that hamper the application of phage therapy because they can lead to the rapid acquisition of phage resistance. In this study, eight anti-phage defense systems were found in the genome of 12 Pf phages that were presents in 56% of the CF isolates of . The high prevalence of these phages underlines the importance of our findings about newly discovered filamentous phages and the role of these phages in resistance to phage infections. Thus, the knowledge of the anti-defense system in the Pf phage genomes could be useful in assessing the possible application of phage therapy to treat an infectious disease.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878078 | PMC |
http://dx.doi.org/10.1128/spectrum.03010-24 | DOI Listing |
Nat Commun
March 2025
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Bacterial antiviral STANDs (Avs) are evolutionarily related to the nucleotide-binding oligomerization domain (NOD)-like receptors widely distributed in immune systems across animals and plants. EfAvs5, a type 5 Avs from Escherichia fergusonii, contains an N-terminal SIR2 effector domain, a NOD, and a C-terminal sensor domain, conferring protection against diverse phage invasions. Despite the established roles of SIR2 and STAND in prokaryotic and eukaryotic immunity, the mechanism underlying their collaboration remains unclear.
View Article and Find Full Text PDFNat Commun
March 2025
Center for Structural Biology, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD, USA.
Bacteria have evolved an extraordinary diversity of defense systems against bacteriophage (phage) predation. However, the molecular mechanisms underlying these anti-phage systems often remain elusive. Here, we provide mechanistic and structural insights into Zorya phage defense systems.
View Article and Find Full Text PDFbioRxiv
February 2025
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.
The rise of antibiotic resistance motivates a revived interest in phage therapy. However, bacteria possess dozens of anti-bacteriophage immune systems that confer resistance to therapeutic phages. Chemical inhibitors of these anti-phage immune systems could be employed as adjuvants to overcome resistance in phage-based therapies.
View Article and Find Full Text PDFMicrobiol Res
June 2025
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China. Electronic address:
The rapid spread of multidrug-resistant bacteria and the challenges in developing new antibiotics have brought renewed international attention to phage therapy. However, in bacteria-phage co-evolution, the rapid development of bacterial resistance to phage has limited its clinical application. This review consolidates the latest advancements in research on anti-phage mechanisms, encompassing strategies such as systems associated with reduced nicotinamide adenine dinucleotide (NAD) to halt the propagation of the phage, symbiotic bacteria episymbiont-mediated modulation of gene expression in host bacteria to resist phage infection, and defence-related reverse transcriptase (DRT) encoded by bacteria to curb phage infections.
View Article and Find Full Text PDFMol Cell
February 2025
Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA; Program of OSBP, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA. Electronic address:
Leveraging AlphaFold models and integrated experiments, we characterized the HerA-DUF4297 (DUF) anti-phage defense system, focusing on DUF's undefined biochemical functions. Guided by structure-based genomic analyses, we found DUF homologs to be universally distributed across diverse bacterial immune systems. Notably, one such homolog, Cap4, is a nuclease.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!