Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 26, 2025

Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about dormancy development recovery. Previously, established a correlation between protein aggregation in Escherichia coli. Here, present further support for direct relationship both. Our experiments demonstrate that aggregates progressively sequester proteins involved energy production, thereby likely causing ATP depletion dormancy. Furthermore, structural features determine the cell's ability to exit resume growth. Proteins were shown first assemble liquid-like condensates solidify over time. This liquid-to-solid phase transition impedes aggregate dissolution, preventing growth resumption. data model which structure, rather than cellular activity, marks from persister VBNC state. are often authors explore how composition structure affect this

Язык: Английский

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Environmental, mechanistic and evolutionary landscape of antibiotic persistence

EMBO Reports, Год журнала: 2023, Номер 24(8)

Опубликована: Июль 3, 2023

Язык: Английский

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The rise and future of CRISPR-based approaches for high-throughput genomics

FEMS Microbiology Reviews, Год журнала: 2024, Номер 48(5)

Опубликована: Июль 31, 2024

Clustered regularly interspaced short palindromic repeats (CRISPR) has revolutionized the field of genome editing. To circumvent permanent modifications made by traditional CRISPR techniques and facilitate study both essential nonessential genes, interference (CRISPRi) was developed. This gene-silencing technique employs a deactivated Cas effector protein guide RNA to block transcription initiation or elongation. Continuous improvements better understanding mechanism CRISPRi have expanded its scope, facilitating genome-wide high-throughput screens investigate genetic basis phenotypes. Additionally, emerging CRISPR-based alternatives further possibilities for screening. review delves into CRISPRi, compares it with other gene-perturbation techniques, highlights superior capacities studying complex microbial traits. We also explore evolution emphasizing enhancements that increased capabilities, including multiplexing, inducibility, titratability, predictable knockdown efficacy, adaptability nonmodel microorganisms. Beyond we discuss activation, RNA-targeting systems, single-nucleotide resolution perturbation their potential in Collectively, this gives comprehensive overview general workflow screen, an extensive discussion strengths weaknesses, future directions, alternatives.

Язык: Английский

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Biofilm Formation, Antibiotic Resistance, and Infection (BARI): The Triangle of Death

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(19), С. 5779 - 5779

Опубликована: Сен. 27, 2024

Fracture-related infection (FRI) is a devastating event, directly affecting fracture healing, impairing patient function, prolonging treatment, and increasing healthcare costs. Time plays decisive role in prognosis, as biofilm maturation leads to the development of antibiotic resistance, potentially contributing chronicity morbidity mortality. Research exploring association between resistance orthopaedics primarily addresses aspects related quality life physical function; however, little exists on life-threatening conditions Understanding intrinsic relationship maturation, bacterial mortality critical all fields medicine. In herein narrative review, we summarize recent evidence regarding formation, (BARI), three basic components “triangle death” FRI, its implications. Preoperative, perioperative, postoperative prevention strategies avoid FRI are presented discussed. Additionally, importance orthopaedic trauma surgeon understanding new tools combat infections devices highlighted.

Язык: Английский

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Intoxication of antibiotic persisters by host RNS inactivates their efflux machinery during infection

PLoS Pathogens, Год журнала: 2024, Номер 20(2), С. e1012033 - e1012033

Опубликована: Фев. 29, 2024

The host environment is of critical importance for antibiotic efficacy. By impacting bacterial machineries, stresses encountered by pathogens during infection promote the formation phenotypic variants that are transiently insensitive to action antibiotics. It assumed these recalcitrant bacteria—termed persisters—contribute treatment failure and relapsing infections. Recently, we demonstrated reactive nitrogen species (RNS) protect persisters against β-lactam antibiotics delaying their regrowth within cells. Here, discovered RNS intoxication also collaterally sensitizing them fluoroquinolones infection, explaining higher efficiency intramacrophage Salmonella . reducing respiration proton-motive force, inactivate AcrAB efflux machinery persisters, facilitating accumulation intracellularly. Our work shows target inactivity not sole reason withstand with active being a major contributor survival. Thus, understanding how impacts persister physiology optimize efficacy infection.

Язык: Английский

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Effects of Alhagi camelorum Fisch polysaccharide from different regions on growth performance and gastrointestinal microbiota of sheep lambs

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Апрель 30, 2024

Polysaccharides derived from Alhagi camelorum Fisch possess diverse activities, making them a potential prebiotic candidates for enhancing lamb health. This study investigated the immunomodulatory effects of polysaccharides Aksu (AK) and Shanshan (SS) regions on sheep lambs. The results showed that lambs in SS group exhibited significantly increased ( p < 0.05) average daily gain, levels growth hormone (GH), insulin (INS), IgA IgM, cytokines IL-4, IL-10, IL-17, TNF-α IFN-γ compared to those control check (CK) group. Moreover, treatment diversity abundance beneficial bacteria, while concurrently diminishing prevalence harmful bacteria. Additionally, it modulated various metabolic pathways, promoted growth, improved immunity, reduced risk gastrointestinal disease composition microbiota. In summary, our findings highlight health by improving intestinal function, gut microbiome. Consequently, these suggest holds promising as valuable intervention optimizing performance

Язык: Английский

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Heterogeneous efflux pump expression underpins phenotypic resistance to antimicrobial peptides

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

Опубликована: Апрель 22, 2024

Antimicrobial resistance threatens the viability of modern medical interventions. There is a dire need developing novel approaches to counter mechanisms employed by starved or slow-growing pathogens that are refractory conventional antimicrobial therapies. peptides have been advocated as potential therapeutic solutions due low levels genetic observed in bacteria against these compounds. However, here we show subpopulations stationary phase Escherichia coli and Pseudomonas aeruginosa survive tachyplesin treatment without mutations. These phenotypic variants induce efflux, outer membrane vesicles secretion modifications response exposure, sequestering peptide their membranes where it cannot exert its activity. We discovered formation could be prevented administering combination with sertraline, clinically used antidepressant, suggesting approach for combatting antimicrobial-refractory bacteria.

Язык: Английский

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What Is the Impact of Antibiotic Resistance Determinants on the Bacterial Death Rate?

Antibiotics, Год журнала: 2025, Номер 14(2), С. 201 - 201

Опубликована: Фев. 14, 2025

Objectives: Antibiotic-resistant bacteria are widespread, with resistance arising from chromosomal mutations and genes located in the chromosome or mobile genetic elements. While determinants often reduce bacterial growth rates, their influence on death under bactericidal antibiotics remains poorly understood. When exposed to which they susceptible, typically undergo a two-phase decline: fast initial exponentially decaying phase, followed by persistent slow-decaying phase. This study examined how affect rates during both phases. Methods: We analyzed of ampicillin-exposed Escherichia coli populations strains sensitive ampicillin but resistant nalidixic acid, rifampicin, both, carrying conjugative plasmids RN3 R702. Results: Single mutants acid rifampicin decayed faster than cells early whereas double-resistant mutant exhibited prolonged survival. These contrasting impacts suggest epistatic interactions between mutations. Persistent-phase for did not differ significantly wild-type cells. In contrast, plasmid-carrying displayed distinct dynamics: R702 plasmid-bearing showed higher persistent-phase plasmid-free cells, while lower rates. Conclusions: Bactericidal may kill other more effectively Moreover, epistasis occur when different same cell, impacting potential antibiotic choice. results have significant implications optimizing eradication protocols clinical settings, as well animal health industrial food safety management.

Язык: Английский

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Effects of Ficus carica L. polysaccharide on the intestinal immune function and microbiota of broilers

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

Ficus carica L. polysaccharides (FLPs) are groups of biologically active compounds extracted from In this study, we analyzed the structure FLPs, predicted their immune enhancement pathway, and detected impact FLPs on growth performance, function, intestinal microflora broiler chickens. The results showed that comprised monosaccharides including rhamnose, arabinose, mannose, glucose, galactose. Feeding with significantly promoted slaughtering organs index chickens compared to control group (p < 0.05). Moreover, FLP-h FLP-m had increased levels sIgA, IgG, IL-4, IL-5, IL-12, IFN-g; improved immunity barrier function; a higher percentage spleen CD4+ CD8+ T cell differentiation Additionally, various SCFAs, beneficial bacteria such as Firmicutes at phylum level Faecalibacterium, Blautia, Phascolarctobacterium, Alistipes genus level. network pharmacology KEGG pathway prediction indicate may change metabolism microbiota by enhancing carbon fixation pathways in prokaryotes, promote function through joint action bisphenol degradation, retinol metabolism, NODlike signaling pathways, toll-like receptor MAPK pathway. These suggest supplementation effectively promotes performance enhances mucosal

Язык: Английский

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Unraveling Persistent Bacteria: Formation, Niches, and Eradication Strategies

Microbiological Research, Год журнала: 2025, Номер 297, С. 128189 - 128189

Опубликована: Апрель 23, 2025

Язык: Английский

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