Recent advancements in bacterial anti-phage strategies and the underlying mechanisms altering susceptibility to antibiotics

Microbiological Research, Journal Year: 2025, Volume and Issue: 295, P. 128107 - 128107

Published: Feb. 21, 2025

Language: Английский

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Structural basis for the evolution of a domesticated group II intron-like reverse transcriptase to function in host cell DNA repair

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

A previous study found that a domesticated bacterial group II intron-like reverse transcriptase (G2L4 RT) functions in double-strand break repair (DSBR) via microhomology-mediated end joining (MMEJ) and mobile intron-encoded RT has basal DSBR activity uses conserved structural features of non-LTR-retroelement RTs. Here, we determined G2L4 apoenzyme snap-back DNA synthesis structures revealing novel adaptations optimized its cellular function DSBR. These included unique RT3a structure stabilizes the an inactive conformation until encountering appropriate substrate; longer N-terminal extension/RT0-loop with residues together modified active site favors strand annealing; dimer interface localizes homodimers to sites both monomers positioned for MMEJ. Our findings reveal how evolved dedicated suggest new ways optimizing these RTs genome engineering applications.

Language: Английский

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Systematic revelation and meditation on the significance of long exons using representative eukaryotic genomes

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 24, 2025

Long exons/introns are not evenly distributed in the genome, but biological significance of this phenomenon remains elusive. Exon properties were analyzed seven well-annotated reference genomes, including human and other representative model organisms: mouse, fruitfly, worm, mouse-ear cress, corn, rice. In all species, last exons genes tend to be longest. Additionally, we found that (1) canonical splicing motifs strongly underrepresented 3'UTR; (2) Last have low GC content; (3) Comparing with first D. melanogaster demonstrate lower content than internal exons. It cannot excluded exert essential regulatory roles is subjected natural selection, exhibiting differential tendency, compared parts gene body.

Language: Английский

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Structural basis of antiphage defense by an ATPase-associated reverse transcriptase

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Reverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses retrotransposons. However, recent evidence suggests that RTs been conscripted by cells for diverse antiviral defense. Here we determine structures a type I-A retron, which explain how RNA, DNA, RT, HNH-nuclease four molecules an SMC-family ATPase assemble into 364 kDa complex provides phage We show phage-encoded nucleases trigger degradation retron-associated leading to disassembly retron activation HNH nuclease. The nuclease cleaves tRNA Ser , stalling protein synthesis arresting viral replication. Taken together, these data reveal paradoxical perpetuation elimination genetic parasites.

Language: Английский

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Radiophobia Harm, Its Main Cause, and a Proposed Solution

Dose-Response, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 1, 2025

Background: We are exposed to natural ionizing radiation and other genomic stressors throughout life radiophobia has caused much harm society. The main basis for is the invalid linear no-threshold (LNT) hypothesis cancer induction, which System of Radiological Protection (SRP) linked to. Largely unknown public, evolution-associated stress adaptation (gensadaptation) over many previous generations now provides protection all lifeforms from low doses. Objective: To help bring about an improved SRP not LNT radiation-caused health detriment promote low-dose therapy different diseases. Methods: All-solid-cancer mortality risk dose-response relationships A-bomb survivors were generated based on published LNT-modeling-related results. Dose-response lung prevention by interpolation data a study using > 15,000 mice. Uncertainty characterization was Monte Carlo calculations binomial Poisson distributions. New dose tools used threshold mortality. Results: all-solid-cancer transitioned threshold-linear when adjusted key missing uncertainty at in mice doses depends absorbed type. Conclusions: should be population thresholds rather than small likely harmless could possibly treating

Language: Английский

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Tricking phages with a reverse move

Science, Journal Year: 2024, Volume and Issue: 386(6717), P. 25 - 26

Published: Aug. 29, 2024

An antiviral gene is absent in DNA but expressed by rolling circle reverse transcription.

Language: Английский

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A reverse transcriptase controls prophage genome reduction to promote phage dissemination in Pseudomonas aeruginosa biofilms

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114883 - 114883

Published: Oct. 19, 2024

Language: Английский

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Overview of Phage Defense Systems in Bacteria and Their Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13316 - 13316

Published: Dec. 12, 2024

As natural parasites of bacteria, phages have greatly contributed to bacterial evolution owing their persistent threat. Diverse phage resistance systems been developed in bacteria during the coevolutionary process with phages. Conversely, contamination has a devastating effect on microbial fermentation, resulting fermentation failure and substantial economic loss. Accordingly, defense derived from can be employed obtain robust phage-resistant host cells that overcome threats posed by bacteriophages industrial processes. In this review, diverse mechanisms, including remarkable research progress potential applications, are systematically summarized. addition, development prospects challenges discussed. This review provides useful reference for developing bacteria.

Language: Английский

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Intracellularly synthesized ssDNA for continuous genome engineering

Trends in biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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The role of noncoding RNAs in bacterial immunity

Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

HighlightsNoncoding RNAs (ncRNAs) have emerged as pivotal players in bacteria–phage conflicts.Many bacterial immune systems depend on ncRNAs for both structure and function.ncRNAs are key regulators of responses.Phages use to counteract defenses.AbstractThe evolutionary arms race between bacteria phages has driven the development diverse anti-phage defense mechanisms. Recent studies identified noncoding conflicts, including CRISPR-Cas, toxin–antitoxin (TA), reverse transcriptase (RT)-based defenses; however, our understanding their roles immunity is still emerging. In this review, we explore multifaceted immunity, offering insights into contributions anti-defense mechanisms, influence regulatory networks, potential biotechnological applications. Finally, highlight outstanding questions field spark future research directions.

Language: Английский

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