Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis

PLoS Pathogens, Journal Year: 2021, Volume and Issue: 17(5), P. e1009570 - e1009570

Published: May 14, 2021

Mycobacterium tuberculosis ( Mtb ) has complex and dynamic interactions with the human host, subpopulations of that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn 2+ availability as a likely driver bacterial phenotypic heterogeneity in vivo . Zn sequestration is part “nutritional immunity”, where immune system limits micronutrients to control pathogen growth, but this defense mechanism seems be ineffective controlling infection. Nonetheless, -limitation an environmental cue sensed by , calprotectin triggers uptake regulator (Zur) regulon response vitro co-localizes -limited Prolonged limitation leads numerous physiological changes including differential expression certain antigens, alterations lipid metabolism distinct cell surface morphology. Furthermore, enduring limited employ defensive measures fight oxidative stress, increasing proteins involved DNA repair antioxidant activity, well described virulence factors KatG AhpC, along altered utilization redox cofactors. Here, we propose model which prolonged defines population anticipatory adaptations against impending attack, based on evidence are more resistant stress exhibit increased survival induce severe pulmonary granulomas mice. Considering extracellular may transit through caseum before infecting naïve cells or upon host-to-host transmission, resulting driven varied plays key role early host cells.

Language: Английский

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Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115487 - 115487

Published: Sept. 15, 2023

Itaconic acid (IA), a metabolite generated by the tricarboxylic (TCA) cycle in eukaryotic immune cells, and its derivative dimethyl itaconate (DI) exert antibacterial functions intracellular environments. Previous studies suggested that IA DI only inhibit bacterial growth carbon-limited environments; however, whether maintain activity carbon-enriched environments remains unknown. Here, inhibited bacteria with minimum inhibitory concentrations of 24.02 mM 39.52 mM, respectively, environment. The reduced pathogenicity was reflected cell membrane integrity, motility, biofilm formation, AI-2/luxS, virulence. Mechanistically, succinate dehydrogenase (SDH) fumaric levels decreased treatments, while isocitrate lyase (ICL) upregulated. Inhibited TCA circulation also observed through untargeted metabolomics. In addition, energy-related aspartate metabolism lysine degradation were suppressed. summary, these results indicated exerting inhibiting circulation. This study enriches knowledge on inhibition carbon-mixed environment, suggesting an alternative method for treating infections metabolites.

Language: Английский

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Fluorescence Lifetime Imaging Detects Long-Lifetime Signal Associated with Reduced Pyocyanin at the Surface of Pseudomonas aeruginosa Biofilms and in Cross-Feeding Conditions

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Understanding bacterial physiology in real-world environments requires noninvasive approaches and is a challenging yet necessary endeavor to effectively treat infectious disease. Bacteria evolve strategies tolerate chemical gradients associated with infections. The DIVER (Deep Imaging Via Enhanced Recovery) microscope can image autofluorescence fluorescence lifetime throughout samples high optical scattering, enabling the study of naturally formed intact biofilms. Using DIVER, long fluorescent signal reduced pyocyanin, molecule for electron cycling low oxygen, was detected low-oxygen conditions at surface Pseudomonas aeruginosa biofilms presence fermentation metabolites from Rothia mucilaginosa, which cocolonizes infected airways P. aeruginosa. These findings underscore utility studies within complex environments, could inform on more effective managing chronic infection.

Language: Английский

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Antibacterial activity and mechanisms of α-terpineol against foodborne pathogenic bacteria

Applied Microbiology and Biotechnology, Journal Year: 2023, Volume and Issue: 107(21), P. 6641 - 6653

Published: Sept. 8, 2023

Language: Английский

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Review of Fluorescence Lifetime Imaging Microscopy (FLIM) Data Analysis Using Machine Learning

Journal of Experimental and Theoretical Analyses, Journal Year: 2023, Volume and Issue: 1(1), P. 44 - 63

Published: Sept. 21, 2023

Fluorescence lifetime imaging microscopy (FLIM) has emerged as a promising tool for all scientific studies in recent years. However, the utilization of FLIM data requires complex modeling techniques, such curve-fitting procedures. These conventional procedures are not only computationally intensive but also time-consuming. To address this limitation, machine learning (ML), particularly deep (DL), can be employed. This review aims to focus on ML and DL methods analysis. Subsequently, strategies evaluating discussed, consisting preprocessing, modeling, inverse modeling. Additionally, advantages reviewed deliberated alongside future implications. Furthermore, several freely available software packages analyzing highlighted.

Language: Английский

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Formation and emergent dynamics of spatially organized microbial systems

Interface Focus, Journal Year: 2023, Volume and Issue: 13(2)

Published: Feb. 10, 2023

Spatial organization is the norm rather than exception in microbial world. While study of physiology has been dominated by studies well-mixed cultures, there now increasing interest understanding role spatial physiology, coexistence and evolution. Where studied, shown to influence all three these aspects. In this mini review perspective article, we emphasize that dynamics within spatially organized systems (SOMS) are governed feedbacks between local physico-chemical conditions, cell movement, These can give rise emergent dynamics, which need be studied through a combination spatio-temporal measurements mathematical models. We highlight initial formation SOMS their as two open areas investigation for future studies. will benefit from development model mimic natural ones terms species composition structure.

Language: Английский

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Visualizing Oxidative Cellular Stress Induced by Nanoparticles in the Subcytotoxic Range Using Fluorescence Lifetime Imaging

Small, Journal Year: 2018, Volume and Issue: 14(23)

Published: May 4, 2018

Abstract Nanoparticles hold a great promise in biomedical science. However, due to their unique physical and chemical properties they can lead overproduction of intracellular reactive oxygen species (ROS). As an important mechanism nanotoxicity, there is need for sensitive high‐throughput adaptable single‐cell ROS detection methods. Here, fluorescence lifetime imaging microscopy (FLIM) employed (FLIM‐ROX) providing increased sensitivity enabling analysis fixed live cells. FLIM‐ROX owes its the discrimination autofluorescence from reporter dye. The effect subcytotoxic amounts cationic gold nanoparticles J774A.1 cells primary human macrophages on generation investigated. measures very low levels upon nanoparticle exposure, which undetectable by conventional method. It demonstrated that cellular morphology changes, elevated senescence, DNA damage link resulting low‐level oxidative stress adverse effects thus nanotoxicity. Multiphoton enables quantification spatial distribution vivo, shown skin tissue as target exposure. Thus, this innovative method allows identifying vitro vivo and, subsequently, promotes understanding ROS‐associated

Language: Английский

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Machine Learning Methods for Fluorescence Lifetime Imaging (FLIM) Based Label-Free Detection of Microglia

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Sept. 3, 2020

Automated computational analysis techniques utilizing machine learning have been demonstrated to be able extract more data from different imaging modalities compared traditional techniques. One new approach is use existing multiphoton better interpret intrinsically fluorescent cellular signals characterize cell types. Fluorescence Lifetime Imaging Microscopy (FLIM) a high-resolution quantitative tool that can detect metabolic signatures based on the lifetime variations of co-factors such as nicotinamide adenine dinucleotide (NAD(P)H). NAD(P)H lifetime-based discrimination previously used develop for diverse types including immune cells macrophages. However, FLIM could even effective in characterizing if was classify by parameters classification. Here, we demonstrate potential FLIM-based, label-free distinguish using Artificial Neural Network (ANN)-based learning. For our biological case, challenge differentiating microglia other glia brain. Microglia are resident macrophages brain and spinal cord play critical role maintaining neural environment responding injury. challenging identify most labeling approaches cross-react with types, often insensitive activation state, require multiple specialized antibody labels. Furthermore, these extrinsic labels prevents application vivo animal models possible future clinical adaptations neurodegenerative pathologies. With ANN-based approach, found culture mixed glial identified than 0.9 True Positive Rate (TPR). We also extended fixed tissue TPR 0.79. In both cases False Discovery around 30%. This method further potentially study understand microglia's disease improved detection accuracy.

Language: Английский

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Discriminating Bacterial Phenotypes at the Population and Single‐Cell Level: A Comparison of Flow Cytometry and Raman Spectroscopy Fingerprinting

Cytometry Part A, Journal Year: 2019, Volume and Issue: 97(7), P. 713 - 726

Published: Dec. 30, 2019

Abstract Investigating phenotypic heterogeneity can help to better understand and manage microbial communities. However, characterizing remains a challenge, as there is no standardized analysis framework. Several optical tools are available, such flow cytometry Raman spectroscopy, which describe properties of the individual cell. In this work, we compare spectroscopy study in bacterial populations. The growth stages three replicate Escherichia coli populations were characterized using both technologies. Our findings show that detects quantifies shifts at population level due its high‐throughput nature. on other hand, offers much higher resolution single‐cell (i.e., more biochemical information recorded) . Therefore, it identify distinct when coupled with analyses tailored toward data. addition, provides about biomolecules present, be linked cell functionality. We propose computational workflow distinguish between validated approach an external data set. recommend quantify level, perform in‐depth level. © 2019 International Society for Advancement Cytometry

Language: Английский

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Bayesian Statistical Analysis for Bacterial Detection in Pulmonary Endomicroscopic Fluorescence Lifetime Imaging

IEEE Transactions on Image Processing, Journal Year: 2024, Volume and Issue: 33, P. 1241 - 1256

Published: Jan. 1, 2024

Pneumonia, a respiratory disease often caused by bacterial infection in the distal lung, requires rapid and accurate identification, especially settings such as critical care. Initiating or de-escalating antimicrobials should ideally be guided quantification of pathogenic bacteria for effective treatment. Optical endomicroscopy is an emerging technology with potential to expedite detection lung enabling vivo situ optical tissue characterisation. With advancements detector technology, can utilize fluorescence lifetime imaging (FLIM) help detect events that were previously challenging impossible identify using intensity imaging. In this paper, we propose iterative Bayesian approach FLIM. We model FLIM image linear combination background intensity, Gaussian noise, additive outliers (labelled bacteria). While previous methods anomalous pixels bacteria, here are modelled circularly symmetric Gaussian-shaped objects, based on their discrete shape observed through visual analysis physical nature modality. A Hierarchical used solve problem where prior distributions assigned unknown parameters. Metropolis-Hastings within Gibbs sampler draws samples from posterior distribution. The proposed method's performance initially measured synthetic images, shows significant improvement over existing approaches. Further conducted real images annotated trained personnel. experiments show outperforms margin +16.85% ( F ₁ ) accuracy.

Language: Английский

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