Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacersin trans DOI Creative Commons
Fabienne Benz, Sarah Camara-Wilpert, Jakob Russel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 23, 2023

ABSTRACT Type IV-A CRISPR-Cas systems are primarily encoded on plasmids and form multi-subunit ribonucleoprotein complexes with unknown biological functions. In contrast to other types, they lack the archetypical CRISPR acquisition module encode a DinG helicase instead of nuclease component. IV-A3 carried by large conjugative that often harbor multiple antibiotic-resistance genes. Although their array contents suggest role in inter-plasmid conflicts, this function underlying mechanisms have remained unexplored. Here, we demonstrate plasmid-encoded type system co-opts I-E adaptation machinery from its clinical Klebsiella pneumoniae host update array. Furthermore, robust interference phages is elicited through RNA-dependent transcriptional repression. By targeting plasmid core functions, can prevent uptake incoming plasmids, limit horizontal transfer, destabilize co-residing altogether supporting IV-A3’s involvement competition. Collectively, our findings shed light molecular ecological broad implications for understanding countering spread antibiotic resistance clinically relevant strains.

Language: Английский

Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacers in trans DOI
Fabienne Benz, Sarah Camara-Wilpert, Jakob Russel

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(6), P. 875 - 886.e9

Published: May 15, 2024

Language: Английский

Citations

19
Real-time visualisation of the intracellular dynamics of conjugative plasmid transfer DOI Creative Commons
Agathe Couturier, Chloé Virolle, Kelly Goldlust

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 18, 2023

Abstract Conjugation is a contact-dependent mechanism for the transfer of plasmid DNA between bacterial cells, which contributes to dissemination antibiotic resistance. Here, we use live-cell microscopy visualise intracellular dynamics conjugative F-plasmid in E. coli , real time. We show that single-stranded form (ssDNA) and its subsequent conversion into double-stranded (dsDNA) are fast efficient processes occur with specific timing subcellular localisation. Notably, ssDNA-to-dsDNA determines plasmid-encoded protein production. The leading region first enters recipient cell carries promoters allow early transient synthesis proteins immediately upon entry ssDNA plasmid. dsDNA turns off gene expression, activates expression other genes under control conventional promoters. This molecular strategy allows timely production factors sequentially involved establishing, maintaining disseminating

Language: Английский

Citations

41
Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids DOI Creative Commons
Fabienne Benz, Alex R. Hall

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(15)

Published: April 6, 2023

Antibiotic resistance encoded on plasmids is a pressing global health problem. Predicting which spread in the long term remains very challenging, even though some key parameters influencing plasmid stability have been identified, such as growth costs and horizontal transfer rates. Here, we show these evolve strain-specific way among clinical bacteria, this occurs rapidly enough to alter relative likelihoods of different bacterium–plasmid combinations spreading. We used experiments with Escherichia coli antibiotic-resistance isolated from patients, paired mathematical model, track long-term (beyond antibiotic exposure). Explaining variable across six required accounting for evolutionary changes traits, whereas initial variation was relatively poor predictor outcomes. Evolutionary trajectories were specific particular combinations, evidenced by genome sequencing genetic manipulation. This revealed epistatic (here, strain-dependent) effects affecting transfer. Several involved mobile elements pathogenicity islands. Rapid evolution can thus outweigh ancestral phenotypes stability. Accounting natural populations could improve our ability anticipate manage successful combinations.

Language: Английский

Citations

36
Ecological Stability Emerges at the Level of Strains in the Human Gut Microbiome DOI Creative Commons

Richard Wolff,

William R. Shoemaker, Nandita R. Garud

et al.

mBio, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 21, 2023

The human gut microbiome harbors substantial ecological diversity at the species level as well strain within species. In healthy hosts, abundance fluctuations in are thought to be stable, and these can described by macroecological laws. However, it is less clear how abundances change over time. An open question whether individual strains behave like themselves, exhibiting stability following relationships known hold level, or have different dynamics, perhaps due relatively close phylogenetic relatedness of cocolonizing lineages. Here, we analyze daily dynamics intraspecific genetic variation microbiomes four healthy, densely longitudinally sampled hosts. First, find that overall a large majority stationary time despite short-term fluctuations. Next, show approximately 80% analyzed predicted with stochastic logistic model (SLM), an population experiencing environmental around fixed carrying capacity, which has previously been shown capture statistical properties success this indicates typically fluctuate suggesting most dynamically stable. Finally, follow several empirical laws level. Together, our results suggest microbiome, including its stability, emerge strains.

Language: Английский

Citations

35
An overview of novel antimicrobial carbonic anhydrase inhibitors DOI
Claudiu T. Supuran

Expert Opinion on Therapeutic Targets, Journal Year: 2023, Volume and Issue: 27(10), P. 897 - 910

Published: Sept. 25, 2023

Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO2, HCO3-/H+ ions homeostasis, being involved metabolic biosynthetic pathways, pH regulation, represent virulence survival factors for bacteria various niches. Bacterial CAs started be considered druggable targets last decade, as their inhibition impairs survival, growth, these pathogens.Significant advances were registered years designing effective inhibitors sulfonamide type Helicobacter pylori α-CA, Neisseria gonorrhoeae vacomycin-resistant enterococci (VRE) α- γ-CAs, which vivo validation has also been achieved. MIC-s range 0.25-4.0 µg/mL wild drug resistant N. strains, 0.007-2.0 VRE observed some 1,3,4-thiadiazole-2-sulfonamides, acetazolamide was gut decolonization from VRE.Targeting bacterial other pathogens, among Vibrio cholerae, Mycobacterium tuberculosis, Brucella suis, Salmonella enterica serovar Typhimurium, Legionella pneumophila, Porphyromonas gingivalis, Clostridium perfringens, Streptococcus mutans, Burkholderia pseudomallei, Francisella tularensis, Escherichia coli, Mammaliicoccus (Staphylococcus) sciuri, Pseudomonas aeruginosa, may lead novel antibacterials devoid resistance problems.

Language: Английский

Citations

31
Antimicrobial resistance level and conjugation permissiveness shape plasmid distribution in clinical enterobacteria DOI Creative Commons
Aída Alonso-del Valle, Laura Toribio-Celestino, Anna Quirant

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(51)

Published: Dec. 14, 2023

Conjugative plasmids play a key role in the dissemination of antimicrobial resistance (AMR) genes across bacterial pathogens. AMR are widespread clinical settings, but their distribution is not random, and certain associations between clones particularly successful. For example, globally spread carbapenem plasmid pOXA-48 can use wide range enterobacterial species as hosts, it usually associated with small number specific

Language: Английский

Citations

26
Plasmid-encoded insertion sequences promote rapid adaptation in clinical enterobacteria DOI
Jorge Sastre-Dominguez, Javier DelaFuente, Laura Toribio-Celestino

et al.

Nature Ecology & Evolution, Journal Year: 2024, Volume and Issue: 8(11), P. 2097 - 2112

Published: Aug. 28, 2024

Language: Английский

Citations

10
Interspecific competition can drive plasmid loss from a focal species in a microbial community DOI Creative Commons
David Sünderhauf, Uli Klümper, William H. Gaze

et al.

The ISME Journal, Journal Year: 2023, Volume and Issue: 17(10), P. 1765 - 1773

Published: Aug. 10, 2023

Plasmids are key disseminators of antimicrobial resistance genes and virulence factors, it is therefore critical to predict reduce plasmid spread within microbial communities. The cost carriage a metric that can be used plasmids' ecological fate, unclear whether costs affected by growth partners in community. We carried out competition experiments tracked maintenance using model system consisting synthetic stable five-species community broad host-range plasmid, engineered carry different payloads. report both the its long-term focal strain depended on presence competitors, these interactions were species specific. Addition increased high-payload strain, accordingly, loss from occurred over shorter time frame. propose destabilising effect interspecific may leveraged clinical natural environments cure plasmids strains.

Language: Английский

Citations

17
Evolutionary Responses to Acquiring a Multidrug Resistance Plasmid Are Dominated by Metabolic Functions across Diverse Escherichia coli Lineages DOI Creative Commons
Laura Carrilero, Steven Dunn, Robert A. Moran

et al.

mSystems, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 1, 2023

Multidrug resistance (MDR) plasmids drive the spread of antibiotic between bacterial lineages. The immediate impact MDR plasmid acquisition on fitness and cellular processes varies among lineages, but how evolutionary enabling genomic integration vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that response to gaining pLL35 was dominated by chromosomal mutations affecting metabolic regulatory functions, with both strain-specific shared mutational targets. expression several these such as anaerobic metabolism, known be altered upon pLL35. Interactions resident mobile genetic elements, notably IS-elements, potentiated parallel mutations, including insertions upstream

Language: Английский

Citations

15
SMC-based immunity against extrachromosomal DNA elements DOI Creative Commons
Hon Wing Liu, Florian Roisné-Hamelin, Stephan Gruber

et al.

Biochemical Society Transactions, Journal Year: 2023, Volume and Issue: 51(4), P. 1571 - 1583

Published: Aug. 16, 2023

SMC and SMC-like complexes promote chromosome folding genome maintenance in all domains of life. Recently, they were also recognized as factors cellular immunity against foreign DNA. In bacteria archaea, Wadjet Lamassu are anti-plasmid/phage defence systems, while Smc5/6 Rad50 play a role anti-viral humans. This raises an intriguing paradox — how can the same, or closely related, on one hand secure integrity chromosomal DNA, other recognize restrict extrachromosomal DNA? this minireview, we will briefly describe latest understanding each these including speculations principles SMC(-like) function may explain systems linear circular forms invading

Language: Английский

Citations

13