Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(7), P. 1725 - 1737

Published: June 10, 2024

Language: Английский

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Disentangling the feedback loops driving spatial patterning in microbial communities

npj Biofilms and Microbiomes, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 20, 2025

Language: Английский

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In vitro models for studying implant-associated biofilms - A review from the perspective of bioengineering 3D microenvironments

Biomaterials, Journal Year: 2024, Volume and Issue: 309, P. 122578 - 122578

Published: April 21, 2024

Biofilm research has grown exponentially over the last decades, arguably due to their contribution hospital acquired infections when they form on foreign body surfaces such as catheters and implants. Yet, translation of knowledge in laboratory clinic been slow and/or often it is not attempted by teams walk talk what defined 'bench bedside'. We therefore reviewed biofilm literature better understand this gap. Our search revealed substantial development with respect adapting media used models mimic clinical settings, however many vitro were too simplistic, discounting composition properties host microenvironment overlooking biofilm-implant-host interactions. Failure capture physiological growth conditions biofilms vivo results major differences between lab-grown- clinically-relevant biofilms, particularly phenotypic profiles, virulence, antimicrobial resistance, essentially impede bench-to-bedside translatability. In review, we describe complexity biological process at interfaces, discuss prerequisite for characterization that scenario, propose an interdisciplinary outlook how bioengineer converging tissue engineering concepts tools.

Language: Английский

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Structure of thePseudomonas aeruginosaPAO1 Type IV pilus

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 9, 2024

Abstract Type IV pili (T4Ps), which are abundant in many bacterial and archaeal species, have been shown to play important roles both surface sensing twitching motility, with implications for adhesion, biofilm formation pathogenicity. While pilus (T4P) structures from other organisms previously solved, a high-resolution structure of the native, fully assembled T4P Pseudomonas aeruginosa, one major human pathogens, is not available. Here, we report 3.2 Å-resolution P. aeruginosa PAO1 determined by electron cryomicroscopy (cryo-EM). PilA subunits constituting exhibit classical pilin fold featuring an extended N-terminal α-helix linked C-terminal globular β-sheet-containing domain, packed tightly along pilus. The helices constitute core where they stabilise tubular assembly via hydrophobic interactions. α-helical surrounded domain that coats outer pilus, mediating interactions surrounding environment. Comparison organisms, at level pili, allows us enumerate key differences, detect common architectural principles this class prokaryotic filaments. This study provides structural framework understanding molecular cell biology these cellular appendages interaction prokaryotes surfaces.

Language: Английский

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Active layer dynamics drives a transition to biofilm fingering

npj Biofilms and Microbiomes, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 6, 2023

The emergence of spatial organisation in biofilm growth is one the most fundamental topics biophysics and microbiology. It has long been known that growing biofilms can adopt smooth or rough interface morphologies, depending on balance between nutrient supply microbial growth; this 'fingering' transition linked with average width 'active layer' cells at interface. Here we use long-time individual-based simulations to investigate detail driving factors behind biofilm-fingering transition. We show associated dynamical changes active layer. Fingering happens when gaps form layer, which cause local parts pin, become stationary relative moving front. Pinning be transient permanent, leading different morphologies. By constructing a phase diagram for transition, controlling factor magnitude fluctuations layer thickness, rather than thickness per se. Taken together, our work suggests central role dynamics pinning hence morphology.

Language: Английский

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Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: May 17, 2023

For those born with cystic fibrosis (CF), hyper-concentrated mucus a dysfunctional structure significantly impacts CF airways, providing perfect environment for bacterial colonization and subsequent chronic infection. Early treatment antibiotics limits the prevalence of pathogens but permanently alters airway microenvironment, resulting in antibiotic resistance other long-term consequences. With little investment into new traditional antibiotics, safe effective alternative therapeutic options are urgently needed. One gathering significant traction is bacteriophage (phage) therapy. However, known about which phages respiratory infections, dynamics involved between phage(s) host airway, associated by-products, including mucus. Work utilizing gut cell models suggest that adhere to components, reducing microbial non-host-derived immune protection. Thus, retained layer result from positive selection enables them remain layer. Phages bind weakly slowing down diffusion motion increasing their chance encountering species Adherence phage could also facilitate enrichment persistence within potent phenotype or vice versa. how microenvironment responds functionality remains unknown. This review discusses lung diseases, impact mucus, It then potential phages, dynamic relationship whether this may enhance hinder infections CF.

Language: Английский

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Revealing quorum-sensing networks in Pseudomonas aeruginosa infections through internal and external signals to prevent new resistance trends

Microbiological Research, Journal Year: 2024, Volume and Issue: 289, P. 127915 - 127915

Published: Sept. 24, 2024

Language: Английский

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Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(12), P. 3284 - 3303

Published: Oct. 25, 2024

Language: Английский

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Multi-strain phage induced clearance of bacterial infections

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(2), P. e1012793 - e1012793

Published: Feb. 4, 2025

Bacteriophage (or ‘phage’ – viruses that infect and kill bacteria) are increasingly considered as a therapeutic alternative to treat antibiotic-resistant bacterial infections. However, bacteria can evolve resistance phage, presenting significant challenge the near- long-term success of phage therapeutics. Application mixtures multiple phages ( i.e. , ‘cocktails’) has been proposed limit emergence phage-resistant mutants could lead failure. Here, we combine theory computational models in vivo therapy study efficacy cocktail, composed two complementary motivated by example Pseudomonas aeruginosa facing exploit different surface receptors, LUZ19v PAK_P1. As confirmed Luria-Delbr�ck fluctuation test, this motivating serves model for instances where extremely unlikely develop simultaneous mutations against both phages. We then quantify outcomes given single- or double-phage treatment models, function traits host immune strength. Building upon prior work showing monophage immunocompetent hosts, here show cocktails comprised targeting independent receptors improve outcome immunocompromised hosts reduce chance pathogens simultaneously combinations. The finding cocktail is qualitatively robust differences virus-bacteria interactions dynamics. Altogether, combined use analysis highlights influence viral life history receptor complementarity when designing deploying hosts.

Language: Английский

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Decoding host-microbe interactions with engineered human organoids

The EMBO Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

As the antimicrobial resistance crisis becomes a reality, we are only now realizing lack fundamental understanding of mechanisms by which major pathogens infect their human host. To address this, must employ novel methodologies that allow us to investigate microbial behavior in infection-like contexts. Here, present framework for studying host-microbe interactions integrating human-derived organoids with high-resolution live imaging and high-throughput sequencing technologies. This interdisciplinary multiscale strategy has potential resolve great detail under conditions replicating those encountered vivo. Thus, infection studies based on organoid models could open new avenues translational research therapeutic potential.

Language: Английский

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