Candida albicans and Candida glabrata : global priority pathogens

Microbiology and Molecular Biology Reviews, Год журнала: 2024, Номер 88(2)

Опубликована: Июнь 4, 2024

SUMMARYA significant increase in the incidence of

Язык: Английский

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Multiplicity of type 6 secretion system toxins limits the evolution of resistance

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(2)

Опубликована: Янв. 9, 2025

The bacterial type 6 secretion system (T6SS) is a toxin-injecting nanoweapon that mediates competition in plant- and animal-associated microbial communities. Bacteria can evolve de novo resistance against T6SS attacks, but far from universal natural communities, suggesting key features of weaponry may act to limit its evolution. Here, we combine ecoevolutionary modeling experimental evolution examine how toxin multiplicity Acinetobacter baylyi attackers shape susceptible Escherichia coli competitors. In both our models experiments, find combinations multiple distinct toxins by creating genetic bottlenecks, driving resistant lineages extinct before they reach high frequency. We also show that, paradoxically, single-toxin drive the cross-resistance, protecting bacteria unfamiliar combinations, even though such evolutionary pathways were inaccessible multitoxin attackers. Our findings indicate comparable antimicrobial anticancer combination therapies, arsenals function competing microbes. This helps us understand why T6SSs remain widespread effective weapons many T6SS-armed encode functionally diverse anticompetitor toxins.

Язык: Английский

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Activity, delivery, and diversity of Type VI secretion effectors

Molecular Microbiology, Год журнала: 2020, Номер 115(3), С. 383 - 394

Опубликована: Ноя. 21, 2020

The bacterial type VI secretion system (T6SS) is a contractile apparatus that delivers proteins to neighboring or eukaryotic cells. Antibacterial effectors are mostly toxins inhibit the growth of other species and help dominate niche. A broad variety these cause cell lysis prey by disrupting envelope. Other delivered into cytoplasm where they affect DNA integrity, division exhaust energy resources. modular nature T6SS machinery allows different means recruitment toxic secreted inner tube spike components act as carriers. Toxic can be translationally fused interact with them through specialized structural domains. These interactions also assisted dedicated chaperone proteins. Moreover, conserved sequence motifs in effector-associated domains subject genetic rearrangements therefore engage diversification arsenal effectors. This review discusses diversity presents current knowledge about their loading on machinery.

Язык: Английский

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The ecological impact of a bacterial weapon: microbial interactions and the Type VI secretion system

FEMS Microbiology Reviews, Год журнала: 2021, Номер 45(6)

Опубликована: Июнь 20, 2021

Bacteria inhabit all known ecological niches and establish interactions with organisms from kingdoms of life. These are mediated by a wide variety mechanisms very often involve the secretion diverse molecules bacterial cells. The Type VI system (T6SS) is protein that uses bacteriophage-like machinery to secrete array effectors, usually translocating them directly into neighbouring effectors display toxic activity in recipient cell, making T6SS an effective weapon during inter-bacterial competition eukaryotic Over last two decades, microbiology research has experienced shift towards using systems-based approaches study between their communities context. Here, we focus on this aspect T6SS. We consider how our perspective developed examine what currently about impact bacteria deploying can have environments, including associated plants, insects mammals. T6SS-mediated affect host shaping microbiota, as well be established different microorganisms through deployment versatile system.

Язык: Английский

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Pathogenicity and virulence of Acinetobacter baumannii : Factors contributing to the fitness in healthcare settings and the infected host

Virulence, Год журнала: 2023, Номер 15(1)

Опубликована: Дек. 6, 2023

Acinetobacter baumannii is a common cause of healthcare-associated infections and hospital outbreaks, particularly in intensive care units. Much the success A. relies on its genomic plasticity, which allows rapid adaptation to adversity stress. The capacity acquire novel antibiotic resistance determinants tolerance stresses encountered environment promote spread among patients long-term contamination healthcare setting. This review explores virulence factors physiological traits contributing infection environment. Several cell-associated secreted involved biofilm formation, cell adhesion, invasion, persistence host, as well xeric stress imposed by settings, are illustrated give reasons for pathogen.

Язык: Английский

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Killing in the name of: T6SS structure and effector diversity

Microbiology, Год журнала: 2023, Номер 169(7)

Опубликована: Июль 25, 2023

The life of bacteria is challenging, to endure employ a range mechanisms optimize their environment, including deploying the type VI secretion system (T6SS). Acting as bacterial crossbow, this delivers effectors responsible for subverting host cells, killing competitors and facilitating general access common goods. Due its importance, lethal machine has been evolutionarily maintained, disseminated specialized fulfil these vital functions. In fact, T6SS structural clusters are present in over 25 % Gram-negative bacteria, varying number from one six different genetic per organism. Since discovery 2006, research on rapidly progressed, yielding remarkable breakthroughs. identification characterization novel components T6SS, combined with biochemical studies, have revealed fascinating governing assembly, loading, firing disassembly processes. Recent findings also demonstrated efficacy against fungal Gram-positive expanding scope. Ongoing continues uncover an extensive repertoire effectors, genuine mediators function. These studies shedding light new aspects biology prokaryotic eukaryotic organisms. This review provides comprehensive overview highlighting recent discoveries structure diversity effectors. Additionally, it injects personal perspective avenues future research, aiming deepen our understanding combative system.

Язык: Английский

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Pangenomic analysis reveals plant NAD ⁺ manipulation as an important virulence activity of bacterial pathogen effectors

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(7)

Опубликована: Фев. 8, 2023

Nicotinamide adenine dinucleotide (NAD + ) has emerged as a key component in prokaryotic and eukaryotic immune systems. The recent discovery that Toll/interleukin-1 receptor (TIR) proteins function NAD hydrolases (NADase) links -derived small molecules with signaling. We investigated pathogen manipulation of host metabolism virulence strategy. Using the pangenome model bacterial Pseudomonas syringae , we conducted structure-based similarity search from 35,000 orthogroups for type III effectors (T3Es) potential NADase activity. Thirteen T3Es, including five newly identified candidates, were possess domain(s) characteristic seven -hydrolyzing enzyme families. Most strains depend on secretion system to cause disease, encode at least one -manipulating T3E, many have several. experimentally confirmed III-dependent novel named HopBY, which shows structural both TIR adenosine diphosphate ribose (ADPR) cyclase. Homologs HopBY predicted be VI diverse species, indicating recruitment this activity by microbial secreted during various interspecies interactions. efficiently hydrolyzes specifically produces 2′cADPR, can also produced receptors plants other bacteria. Intriguingly, effector promoted virulence, 2′cADPR may not signaling molecule directly initiates immunity. This study highlights host-pathogen battleground centered around provides insight into involved plant

Язык: Английский

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Bacterial type VI secretion system (T6SS): an evolved molecular weapon with diverse functionality

Biotechnology Letters, Год журнала: 2023, Номер 45(3), С. 309 - 331

Опубликована: Янв. 23, 2023

Язык: Английский

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A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Фев. 16, 2023

Abstract Bacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS also be injected into eukaryotic cells to facilitate bacterial survival, often targeting cytoskeleton. Here, we show that trans-kingdom antimicrobial effector VgrG4 from Klebsiella pneumoniae triggers fragmentation mitochondrial network. colocalizes with endoplasmic reticulum (ER) protein mitofusin 2. induces transfer Ca 2+ ER mitochondria, activating Drp1 (a regulator fission) thus leading network fragmentation. elevation activation innate immunity receptor NLRX1 produce reactive oxygen species (ROS). NLRX1-induced ROS limits NF-κB modulating degradation inhibitor IκBα. The IκBα is triggered ubiquitin ligase SCF β-TrCP , which requires modification cullin-1 subunit NEDD8. abrogates NEDDylation inactivation Ubc12, NEDD8-conjugating enzyme. Our work provides an example manipulation via alteration mitochondria.

Язык: Английский

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Identification of type VI secretion system effector-immunity pairs using structural bioinformatics

Molecular Systems Biology, Год журнала: 2024, Номер 20(6), С. 702 - 718

Опубликована: Апрель 24, 2024

Abstract The type VI secretion system (T6SS) is an important mediator of microbe–microbe and microbe–host interactions. Gram-negative bacteria use the T6SS to inject effectors (T6Es), which are usually proteins with toxic activity, into neighboring cells. Antibacterial have cognate immunity that neutralize self-intoxication. Here, we applied novel structural bioinformatic tools perform systematic discovery functional annotation T6Es their from a dataset 17,920 T6SS-encoding bacterial genomes. Using clustering, identified 517 putative T6E families, outperforming sequence-based clustering. We developed logistic regression model reliably quantify protein–protein interaction new T6E-immunity pairs, yielding candidate for 231 out families. used sensitive structure-based yielded annotations 51% again annotation. Next, validated four pairs using basic experiments in E. coli . In particular, showed Pfam domain DUF3289 homolog Colicin M DUF943 acts as its protein. Furthermore, discovered SleB, lytic transglycosylase, specific glutamate catalytic residue. Overall, this study applies pair discovery, provides extensive database annotated pairs.

Язык: Английский

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