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Current Genetics Feb 2016In textbooks, DNA is generally defined as the universal storage material for genetic information in all branches of life. Beyond this important intracellular role, DNA... (Review)
Review
In textbooks, DNA is generally defined as the universal storage material for genetic information in all branches of life. Beyond this important intracellular role, DNA can also be present outside of living cells and is an abundant biopolymer in aquatic and terrestrial ecosystems. The origin of extracellular DNA in such ecological niches is diverse: it can be actively secreted or released by prokaryotic and eukaryotic cells by means of autolysis, apoptosis, necrosis, bacterial secretion systems or found in association with extracellular bacterial membrane vesicles. Especially for bacteria, extracellular DNA represents a significant and convenient element that can be enzymatically modulated and utilized for multiple purposes. Herein, we discuss briefly the main origins of extracellular DNA and the most relevant roles for the bacterial physiology, such as biofilm formation, nutrient source, antimicrobial means and horizontal gene transfer.
Topics: Bacterial Physiological Phenomena; Biofilms; DNA, Bacterial; Energy Metabolism; Extracellular Matrix; Extracellular Space; Gene Transfer, Horizontal; Quorum Sensing
PubMed: 26328805
DOI: 10.1007/s00294-015-0514-x -
Frontiers in Cellular and Infection... 2023is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The QS...
is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The QS system of is responsible for the biosynthesis of diverse 2-alkyl-4-quinolones (AQs), of which 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4()-quinolone (PQS) function as QS signal molecules. Transcriptomic analyses revealed that HHQ and PQS influenced the expression of multiple genes via PqsR-dependent and -independent pathways whereas 2-heptyl-4-hydroxyquinoline -oxide (HQNO) had no effect on transcriptome. HQNO is a cytochrome inhibitor that causes programmed cell death and autolysis. However, mutants unable to synthesize HQNO undergo autolysis when grown as colony biofilms. The mechanism by which such autolysis occurs is not understood. Through the generation and phenotypic characterization of multiple PAO1 mutants producing altered levels of AQs in different combinations, we demonstrate that mutation of results in the accumulation of HHQ which in turn leads to Pf4 prophage activation and consequently autolysis. Notably, the effect of HHQ on Pf4 activation is not mediated its cognate receptor PqsR. These data indicate that the synthesis of HQNO in PAO1 limits HHQ-induced autolysis mediated by Pf4 in colony biofilms. A similar phenomenon is shown to occur in cystic fibrosis (CF) isolates, in which the autolytic phenotype can be abrogated by ectopic expression of .
Topics: Humans; Quinolones; Quorum Sensing; Pseudomonas aeruginosa; Prophages; Biofilms; Autolysis
PubMed: 37305419
DOI: 10.3389/fcimb.2023.1183681 -
Journal of Leukocyte Biology Jan 2017Antibiotics have proven to be enormously effective tools in combating infectious diseases. A common roadblock to the effective use of antibiotics is the development of... (Review)
Review
Antibiotics have proven to be enormously effective tools in combating infectious diseases. A common roadblock to the effective use of antibiotics is the development of antibiotic resistance. We have recently observed that the very mechanism by which methicillin-resistant Staphylococcus aureus (MRSA) becomes antibiotic resistant causes the organism to be more inflammatory to innate immune cells. In this review, we offer some thoughts on the ways in which antibiotics have been observed to influence immune responses to bacteria.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Cell Wall; Humans; Inflammation; Microbial Sensitivity Tests; Microbial Viability
PubMed: 27576461
DOI: 10.1189/jlb.4MR0316-153RR -
Frontiers in Microbiology 2016Death is a universal phenomenon; however, is there "life after death?" This topic has been investigated for centuries but still there are gray areas that have yet to be... (Review)
Review
Death is a universal phenomenon; however, is there "life after death?" This topic has been investigated for centuries but still there are gray areas that have yet to be elucidated. Forensic microbiologists are developing new applications to investigate the dynamic and coordinated changes in microbial activity that occur when a human host dies. There is currently a paucity of explorations of the thanatomicrobiome (thanatos-, Greek for death) and epinecrotic communities (microbial communities residing in and/or moving on the surface of decomposing remains). Ongoing studies can help clarify the structure and function of these postmortem microbiomes. Human microbiome studies have revealed that 75-90% of cells in the body prior to death are microbial. Upon death, putrefaction occurs and is a complicated process encompassing chemical degradation and autolysis of cells. Decomposition also involves the release of contents of the intestines due to enzymes under the effects of abiotic and biotic factors. These factors likely have predictable effects on postmortem microbial communities and can be leveraged for forensic studies. This mini review provides a critical examination of emerging research relating to thanatomicrobiome and epinecrotic communities, how each is studied, and possible strategies of stochastic processes.
PubMed: 26941736
DOI: 10.3389/fmicb.2016.00225 -
Frontiers in Immunology 2021Cell-free DNA (cfDNA) is the major structural component of neutrophil extracellular traps (NETs), an innate immune response to infection. Antimicrobial proteins and...
Cell-free DNA (cfDNA) is the major structural component of neutrophil extracellular traps (NETs), an innate immune response to infection. Antimicrobial proteins and peptides bound to cfDNA play a critical role in the bactericidal property of NETs. Recent studies have shown that NETs have procoagulant activity, wherein cfDNA triggers thrombin generation through activation of the intrinsic pathway of coagulation. We have recently shown that thrombin binds to NETs and consequently can alter the proteome of NETs. However, the effect of NETs on thrombin is still unknown. In this study, we report that DNA binding leads to thrombin autolysis and generation of multiple thrombin-derived C-terminal peptides (TCPs) Employing a 25-residue prototypic TCP, GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), we show that TCPs bind NETs, thus conferring mutual protection against nuclease and protease degradation. Together, our results demonstrate the complex interplay between coagulation, NET formation, and thrombin cleavage and identify a previously undisclosed mechanism for formation of TCPs.
Topics: Blood Coagulation; Cell-Free Nucleic Acids; Extracellular Traps; Humans; Immunity, Innate; Neutrophils; Peptide Fragments; Protein Binding; Proteolysis; Spectrum Analysis; Thrombin
PubMed: 33717072
DOI: 10.3389/fimmu.2021.593020 -
Nature Communications Feb 2024Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a...
Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia.
Topics: T-Lymphocytes, Cytotoxic; Perforin; Pore Forming Cytotoxic Proteins; Cytotoxicity, Immunologic
PubMed: 38360940
DOI: 10.1038/s41467-024-45750-w -
Nature Communications Jul 2023Proteins with a catalytically inactive LytM-type endopeptidase domain are important regulators of cell wall-degrading enzymes in bacteria. Here, we study their...
Proteins with a catalytically inactive LytM-type endopeptidase domain are important regulators of cell wall-degrading enzymes in bacteria. Here, we study their representative DipM, a factor promoting cell division in Caulobacter crescentus. We show that the LytM domain of DipM interacts with multiple autolysins, including the soluble lytic transglycosylases SdpA and SdpB, the amidase AmiC and the putative carboxypeptidase CrbA, and stimulates the activities of SdpA and AmiC. Its crystal structure reveals a conserved groove, which is predicted to represent the docking site for autolysins by modeling studies. Mutations in this groove indeed abolish the function of DipM in vivo and its interaction with AmiC and SdpA in vitro. Notably, DipM and its targets SdpA and SdpB stimulate each other's recruitment to midcell, establishing a self-reinforcing cycle that gradually increases autolytic activity as cytokinesis progresses. DipM thus coordinates different peptidoglycan-remodeling pathways to ensure proper cell constriction and daughter cell separation.
Topics: Humans; N-Acetylmuramoyl-L-alanine Amidase; Caulobacter crescentus; Feedback; Constriction; Autolysis
PubMed: 37433794
DOI: 10.1038/s41467-023-39783-w -
Journal of Oral and Maxillofacial... 2023According to Codex Alimentarius, 'Honey is the natural sweet substance, produced by honeybees from the nectar of plants or from secretions of living parts of plants, or... (Review)
Review
According to Codex Alimentarius, 'Honey is the natural sweet substance, produced by honeybees from the nectar of plants or from secretions of living parts of plants, or excretions of plant-sucking insects on the living parts of plants, which the bees collect, transform by combining with specific substances of their own, deposit, dehydrate, store and leave in honeycombs to ripen and mature'. It can also penetrate deep into the tissue and can prevent autolysis and putrefaction. This paper highlights the usefulness of honey as an embalming agent.
PubMed: 38033935
DOI: 10.4103/jomfp.jomfp_42_23 -
Journal of Veterinary Diagnostic... Sep 2021Estimation of the postmortem interval (PMI) is a poorly studied field in veterinary pathology. The development of field-applicable methods is needed given that animal...
Estimation of the postmortem interval (PMI) is a poorly studied field in veterinary pathology. The development of field-applicable methods is needed given that animal cruelty investigations are increasing continually. We evaluated various histologic criteria in equine brain, liver, and muscle tissue to aid the estimation of PMI in horses, which is central to forensic investigations of suspicious death. After death, autolysis proceeds predictably, depending on environmental conditions. Currently, no field-applied methods exist that accurately estimate the PMI using histology in animals or humans through quantification of autolysis. Brain, liver, and skeletal muscle from 12 freshly euthanized horses were held at 22°C and 8°C for 72 h. Tissues were sampled at T0h, T1h, T2h, T4h, T6h, T12h, T24h, T36h, T48h, T60h, and T72h. For each tissue, we quantified 5 to 7 criteria associated with autolysis, based on the percentage of microscopic field involved. Each criterion was modeled, with temperature and time as independent variables. Changes were most predictable in liver and muscle over the first 72 h postmortem. The criteria for autolysis that were present most extensively at both temperatures were hepatocyte individualization and the separation of bile duct epithelium from the basement membrane. The changes that were present next most extensively were disruption of myofiber continuity, hypereosinophilia, and loss of striation. Brain changes were highly variable. The high statistical correlation between the parameter "autolysis" and the variables "time/temperature", indicates that autolysis is progressive and predictable. Further investigation of these criteria is needed to establish histologic algorithms for PMI.
Topics: Animals; Autopsy; Feasibility Studies; Forensic Pathology; Horse Diseases; Horses; Muscle, Skeletal; Postmortem Changes
PubMed: 34109897
DOI: 10.1177/10406387211021865 -
Microbial Cell Factories Aug 2014The cell wall of Gram-positive bacteria is a complex assemblage of glycopolymers and proteins. It consists of a thick peptidoglycan sacculus that surrounds the... (Review)
Review
The cell wall of Gram-positive bacteria is a complex assemblage of glycopolymers and proteins. It consists of a thick peptidoglycan sacculus that surrounds the cytoplasmic membrane and that is decorated with teichoic acids, polysaccharides, and proteins. It plays a major role in bacterial physiology since it maintains cell shape and integrity during growth and division; in addition, it acts as the interface between the bacterium and its environment. Lactic acid bacteria (LAB) are traditionally and widely used to ferment food, and they are also the subject of more and more research because of their potential health-related benefits. It is now recognized that understanding the composition, structure, and properties of LAB cell walls is a crucial part of developing technological and health applications using these bacteria. In this review, we examine the different components of the Gram-positive cell wall: peptidoglycan, teichoic acids, polysaccharides, and proteins. We present recent findings regarding the structure and function of these complex compounds, results that have emerged thanks to the tandem development of structural analysis and whole genome sequencing. Although general structures and biosynthesis pathways are conserved among Gram-positive bacteria, studies have revealed that LAB cell walls demonstrate unique properties; these studies have yielded some notable, fundamental, and novel findings. Given the potential of this research to contribute to future applied strategies, in our discussion of the role played by cell wall components in LAB physiology, we pay special attention to the mechanisms controlling bacterial autolysis, bacterial sensitivity to bacteriophages and the mechanisms underlying interactions between probiotic bacteria and their hosts.
Topics: Acetylation; Bacterial Proteins; Cell Wall; Host-Pathogen Interactions; Lactobacillaceae; Lipopolysaccharides; Peptidoglycan; Polysaccharides, Bacterial; Teichoic Acids
PubMed: 25186919
DOI: 10.1186/1475-2859-13-S1-S9