Isolation, Characterization, and Unlocking the Potential of Mimir124 Phage for Personalized Treatment of Difficult, Multidrug-Resistant Uropathogenic E. coli Strain DOI Open Access
Alla K. Golomidova, Yu A Kupriyanov,

Ruslan Gabdrakhmanov

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12755 - 12755

Опубликована: Ноя. 27, 2024

Escherichia coli and its bacteriophages are among the most studied model microorganisms. Bacteriophages for various E. strains can typically be easily isolated from environmental sources, many of these viruses harnessed to combat infections in humans animals. However, some relatively rare pose significant challenges finding suitable phages. The uropathogenic strain UPEC124, a patient suffering neurogenic bladder dysfunction, was found resistant all coliphages our collections, initial attempts isolate new phages failed. Using an improved procedure phage enrichment, we N4-related Mimir124, belonging Gamaleyavirus genus, which able lyse this “difficult” strain. Although Mimir124 is narrow-spectrum phage, it effective individualized treatment patient, leading pathogen eradication. primary receptor O antigen O101 type; consequently, Mimir124-resistant clones were rough (having lost antigen). These clones, however, gained sensitivity that recognize outer membrane proteins as receptors. Despite presence nine potential antiviral systems genome UPEC124 strain, difficulty largely due efficient, non-specific cell surface protection provided by antigen. results highlight importance approach therapy, where narrow host-range phages—typically avoided pre-fabricated cocktails—may instrumental. Furthermore, study illustrates how integrating genomic, structural, functional insights guide development innovative therapeutic strategies, paving way broader applications therapy combating multidrug-resistant bacterial pathogens.

Язык: Английский

Evolution and ecology of anti-defence systems in phages and plasmids DOI Creative Commons
Théophile Niault, Stineke van Houte, Edze R. Westra

и другие.

Current Biology, Год журнала: 2025, Номер 35(1), С. R32 - R44

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

5
Going viral: The role of mobile genetic elements in bacterial immunity DOI
Beatriz Beamud, Fabienne Benz,

David Bikard

и другие.

Cell Host & Microbe, Год журнала: 2024, Номер 32(6), С. 804 - 819

Опубликована: Июнь 1, 2024

Язык: Английский

Процитировано

10
Phage-induced efflux down-regulation boosts antibiotic efficacy DOI Creative Commons

Samuel Kraus,

Megan Fletcher,

Urszula Łapińska

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(6), С. e1012361 - e1012361

Опубликована: Июнь 28, 2024

The interactions between a virus and its host vary in space time are affected by the presence of molecules that alter physiology either or virus. Determining molecular mechanisms at basis these is paramount for predicting fate bacterial phage populations designing rational phage-antibiotic therapies. We study stationary phase Burkholderia thailandensis ΦBp-AMP1. Although heterogeneous genetic resistance to rapidly emerges B. , enhances efficacy three major antibiotic classes, quinolones, beta-lactams tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. discovered enhanced facilitated reduced efflux phage. This new therapy allows eradication bacteria, whilst requiring concentrations, which crucial treating infections sites where it difficult achieve high concentrations.

Язык: Английский

Процитировано

7
Structure and Activation Mechanism of a Lamassu Phage Defence System DOI Creative Commons
Yan Li, David W. Adams, Hon Wing Liu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Summary Lamassu is a diverse family of defence systems that protect bacteria, including pandemic strains Vibrio cholerae , against phage infection. They target essential cellular processes, aborting infection and preventing propagation by terminating the infected host. The mechanisms which efectors are activated when needed otherwise suppressed unknown. Here, we present structures system from Salmonella enterica . We show an oligomerization domain nuclease efector, LmuA, sequestered two tightly-folded SMC-like LmuB protomers LmuC. Upon activation, liberated LmuA proteins assemble into cyclic homo-tetramer, in four domains brought proximity to create active site capable cleaving DNA. propose tetramer formation likely one-way switch establishes threshold limit potential spontaneous activation cell death. Our findings reveal mechanism defence, involving liberation immune efectors, shed light on how balance potent responses with self-preservation.

Язык: Английский

Процитировано

1
Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems DOI
Baptiste Darracq, Eloi Littner,

Manon Brunie

и другие.

Science, Год журнала: 2025, Номер 388(6747)

Опубликована: Май 8, 2025

Integrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons well known for spreading antibiotic resistance genes, the functions of hundreds cassettes carried sedentary remain largely unexplored. We show many these encode small variants antiphage favor their inclusion in integron. also demonstrate nearly 10% integron pandemic Vibrio cholerae strain novel functions. Most have little or no similarity to previously ones, with several providing defense through cell lysis growth arrest. Our work highlights stabilization prevalence within integrons, making them an untapped biobank mechanisms.

Язык: Английский

Процитировано

1
Invasive bacteriophages between a bell and a hammer: a comprehensive review of pharmacokinetics and bacterial defense systems DOI Creative Commons

Mohammed F Hamdi,

Alyaa Abdulhussein Alsaedi,

Alaa Qasim Hayder

и другие.

Discover Life, Год журнала: 2025, Номер 55(1)

Опубликована: Апрель 3, 2025

Язык: Английский

Процитировано

0
Defence systems drive accessory genome interactions inPseudomonas aeruginosa. DOI Creative Commons
Charlotte E. Chong, Aaron Weimann, Aleksei Agapov

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 6, 2025

Abstract As well as undergoing mutational selection, bacterial genomes are shaped by a complex evolutionary interplay among diverse accessory genome elements (AGEs). In this study we define AGEs encompassing both autonomous including phage, plasmids, integrative conjugative (ICEs) and carried such defence systems (DSs) antimicrobial resistance genes (ARGs). Genomic studies can facilitate our better understanding of the relationships these within microbial genomes, offering deeper insights into their roles in adaptation evolution. Emerging evidence suggests that DSs interact synergistically antagonistically with each other, ecological describe non-random patterns co-occurrence avoidance populations. Here, analysed distributions other recently curated dataset 4,288 Pseudomonas aeruginosa genomes. DS content varied niche, higher numbers per non-CF isolates (average n=7.9) compared to CF n=6.9). We observed multiple phylogenetically independent associations (n=426) dissociations (n=50) DSs, AGEs, many which had plausible biological basis. further explored relative importance interactions different revealing anti-defence engage most significant and, notably, other. Ultimately, variation across niches reveals conflicts shaping provides public resource for downstream on AGE interactions.

Язык: Английский

Процитировано

0
CRISPR/Cas9-Based Genome Editing of Fall Armyworm (Spodoptera frugiperda): Progress and Prospects DOI Creative Commons

Yussuf Mohamed Salum,

Anyuan Yin,

Uroosa Zaheer

и другие.

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1074 - 1074

Опубликована: Авг. 27, 2024

The fall armyworm (Spodoptera frugiperda) poses a substantial threat to many important crops worldwide, emphasizing the need develop and implement advanced technologies for effective pest control. CRISPR/Cas9, derived from bacterial adaptive immune system, is prominent tool used genome editing in living organisms. Due its high specificity adaptability, CRISPR/Cas9 system has been various functional gene studies through knockout applied research engineer phenotypes that may cause economical losses. practical application of diverse insect orders also provided opportunities developing strategies genetic control, such as drive precision-guided sterile technique (pgSIT). In this review, comprehensive overview recent progress S. frugiperda presented. We outline fundamental principles applying embryonic microinjection highlight study genes associated with biological aspects, including body color, insecticide resistance, olfactory behavior, sex determination, development, RNAi. ability technology induce sterility, disrupt developmental stages, influence mating behaviors illustrates roles management strategies. Furthermore, review addresses limitations studying function explores future potential promising controlling pest.

Язык: Английский

Процитировано

2
Kiwa rescues RecBCD for anti-phage activity DOI Creative Commons
Zhiying Zhang,

Thomas C. Todeschini,

Yi Wu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Фев. 26, 2023

Bacteria and archaea deploy diverse, sophisticated defence systems to counter virus infection, yet many immunity mechanisms remain poorly understood. Here, we characterise the Kiwa system as a membrane-associated supercomplex that senses changes in membrane induced by phage infection plasmid conjugation. This supercomplex, comprising KwaA tetramers bound KwaB dimers, its basic repeating unit, detects structural stress via KwaA, activating KwaB, which binds ejected DNA through DUF4868 domain, stalling replication forks thus disrupting late transcription. We show phage-encoded mimic protein Gam, inhibits RecBCD, also targets recognition. However, Gam binding one precludes inhibition of other. These findings reveal distinct mechanism bacterial immune coordination, where sensing disruptions inhibitor partitioning enhance protection against phages plasmids.

Язык: Английский

Процитировано

4
The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease DOI Open Access
Sophie C. Binder, Niels Schneberger, Marianne Engeser

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 8, 2024

Abstract Prokaryotic CRISPR-Cas immune systems detect and cleave foreign nucleic acids. In type III systems, the Cas10 subunit of activated recognition complex synthesizes cyclic oligoadenylates (cOAs), second messengers that activate downstream ancillary effector proteins. Once viral attack has been weathered, elimination extant cOA is essential to limit antiviral response allow cellular recovery. Various families ring nucleases have identified, specializing in degradation cOAs either as standalone enzymes or domains Here we describe nuclease activity inherent SAVED domain cA 4 -activated CRISPR Lon protease CalpL. We characterize kinetics cleavage identify key catalytic residues. demonstrate -incuced oligomerization CalpL not only for activation protease, but also required activity. Further, poses a limitation reaction, indicating mechanism regulation CalpL/T/S signaling cascade. This work first demonstration gives new insights into dynamics transcriptional adaption defense which are aimed at abortive infection rather reversible phage attack.

Язык: Английский

Процитировано

1