The spread of multidrug-resistant Escherichia coli in healthcare facilities is a global challenge. Hospital-acquired infections produced by Escherichia coli include gastrointestinal, blood-borne, urinary tract, surgical sites, and neonatal infections. Therefore, novel approaches are needed to deal with this pathogen and its rising resistance. The concept of attenuating virulence factors is an alternative strategy that might lead to low levels of resistance and combat this pathogen. A sub-inhibitory concentration (1⁄4 MIC) of sitagliptin and nitazoxanide was used for phenotypic assessments of Escherichia coli virulence factors such as biofilm production, swimming motility, serum resistance, and protease production. Moreover, qRT-PCR was used to determine the impact of sub-MIC of the tested drugs on the relative expression levels of papC, fimH, fliC, kpsMTII, ompT_m, and stcE genes encoding virulence factors in Escherichia coli. Also, an in vivo model was conducted as a confirmatory test. Phenotypically, our findings demonstrated that the tested strains showed a significant decrease in all the tested virulence factors. Moreover, the genotypic results showed a significant downregulation in the relative expression levels of all the tested genes. Besides, the examined drugs were found to be effective in protecting mice against Escherichia coli pathogenesis. Sitagliptin and nitazoxanide exhibited strong anti-virulence activities against Escherichia coli. In addition, it is recommended that they might function as adjuvant in the management of Escherichia coli infections with either conventional antimicrobial agents or alone as alternative treatment measures.
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Biofilms drug effects MeSH
- Nitro Compounds MeSH
- Escherichia coli * drug effects pathogenicity genetics MeSH
- Virulence Factors genetics metabolism MeSH
- Escherichia coli Infections * drug therapy microbiology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial MeSH
- Mice MeSH
- Escherichia coli Proteins genetics MeSH
- Sitagliptin Phosphate * pharmacology MeSH
- Thiazoles * pharmacology MeSH
- Virulence drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Narušení mikrobiálního ekosystému člověka představuje významný patogenetický faktor řady onemocnění. Již několik desetiletí je známa úloha alterace střevní mikrobioty v patogenezi rekurentní klostridiové kolitidy. Závažné narušení ve složení nebo funkci mikrobioty (mluvíme o tzv. dysbióze) je dnes nicméně popisováno i v patogenezi dalších chorobných stavů. V tomto smyslu jsou nejčastěji uváděny idiopatické střevní záněty, syndrom dráždivého tračníku, diabetes mellitus 2. typu, roztroušená skleróza, Parkinsonova nemoc, dále také např. jaterní encefalopatie u pacientů s cirhózou jater. Terapeuticky zasáhnout na úrovni poškozené střevní mikrobioty se snažíme různými způsoby. Velmi nadějně se jeví metoda mající za cíl dosáhnout obnovy přirozené mikrobiální homeostázy v tlustém střevě pomocí stolice od zdravého dárce, která je přenesena do zažívacího traktu nemocného. Pro tuto metodu se u nás vžil název "fekální bakterioterapie". V zahraniční literatuře se nejčastěji setkáváme s označením "Fecal Microbiota Transplantation" či se zkratkou FMT.
Disruption of the human microbial ecosystem represents a significant pathogenic factor of many diseases. The role of altered intestinal microbiota in the pathogenesis of recurrent Clostridium difficile colitis has been known for decades. Still, severe disruptions in the composition or function of the microbiota (we are speaking about dysbiosis) is nowadays also described in the pathogenesis of other pathological conditions. In this sense, the most commonly listed are idiopathic inflammatory bowel diseases, irritable bowel syndrome, type 2 diabetes mellitus, multiple sclerosis, Parkinson's disease, furthermore, for example, hepatic encephalopathy in patients with liver cirrhosis. We try to therapeutically intervene on the level of damaged intestinal microbiota in various ways. One very promising method seeks to restore natural microbial homeostasis in the colon using stool from a healthy donor, which is transferred into the digestive tract of the patient. For us, this method became commonly known as "fecal bacteriotherapy". The international literature typically uses the term "Fecal Microbiota Transplantation" or by the abbreviation FMT.
- MeSH
- Drug Resistance, Bacterial MeSH
- Dysbiosis * therapy MeSH
- Fecal Microbiota Transplantation * statistics & numerical data trends MeSH
- Inflammatory Bowel Diseases therapy MeSH
- Humans MeSH
- Central Nervous System Diseases therapy MeSH
- Enterocolitis, Pseudomembranous prevention & control therapy MeSH
- Gastrointestinal Microbiome physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
BACKGROUND/OBJECTIVES: Crohn's disease is known for being associated with an abnormal composition of the bacterial flora, dysbiosis and intestinal function disorders. Metabolites produced by gut microbiota play a pivotal role in the pathogenesis of CD, and the presence of unspecific extraintestinal manifestations. METHODS: The aim of this study was a determination of the level of bacterial metabolites in blood plasma in patients with Crohn's disease. CD patients (29) and healthy individuals (30) were recruited for this study. Bacterial metabolites (SCFAs and TMAO panel) were measured by a liquid chromatography-mass spectrometry system. RESULTS: A significant correlation (p-value < 0.05) between CD and bacterial metabolites was obtained for three of eight tested SCFAs; acetic acid (reduced in CD; FC 1.7; AUC = 0.714), butyric acid (increased; FC 0.68; AUC = 0.717), 2MeBA (FC 1.168; AUC = 0.702), and indoxyl (FC 0.624). The concentration of CA (FC 0.82) and choline (FC 0.78) in plasma was significantly disturbed according to the biological treatment. Choline level (FC 1.28) was also significantly disturbed in the patients treated with glucocorticoids. In total, 68.97% of Crohn's patients presented extraintestinal manifestations (EIMs) of Crohn's disease, mainly osteoarticular complications. The level of BA was statistically significantly elevated in patients with extraintestinal (FC 0.602) manifestations, while in the group of patients with osteoarticular complications, a significant difference in the level of betaine (FC 1.647) was observed. CONCLUSIONS: The analyzed bacterial metabolites of plasma may significantly help in the diagnostic process, and in the monitoring of the disease course and treatment, in a lowly invasive way, as biomarkers after additional research on a larger group of patients.
- MeSH
- Bacteria MeSH
- Biomarkers blood MeSH
- Choline blood MeSH
- Crohn Disease * blood microbiology MeSH
- Adult MeSH
- Dysbiosis blood microbiology MeSH
- Fatty Acids, Volatile blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Methylamines blood MeSH
- Young Adult MeSH
- Gastrointestinal Microbiome * MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Helicobacter pylori patří stále mezi celosvětově nejčastější bakteriální infekce, a to i přes pokles v posledních čtyřech dekádách (v současné době činí cca 40–50 %). Infekce je častější v rozvojových zemích ve srovnání se zeměmi vyspělými. Intenzivní výzkum této chronické infekce objasnil patogenezi řady chorob žaludku i onemocnění extragastrických, včetně karcinomu. Tento článek přináší přehled poznatků o roli Helicobacter pylori u různých maligních chorob žaludku. Chronická infekce Helicobacter pylori je etiologickým faktorem karcinomu žaludku distálně od kardie (non-cardia gastric cancer) a většiny případů žaludečního MALT-lymfomu nízkého stupně. Byla ale popsána inverzní asociace helikobakterové infekce s ostatními žaludečními malignitami, jako jsou karcinom kardie nebo vzácný hereditární syndrom GAPPS (gastric adenocarcinoma and proximal polyposis of the stomach). Dosud nebyla definitivně zodpovězena klíčová otázka, zda časná eradikace infekce Helicobacter pylori je účinnou prevencí vzniku karcinomu žaludku v budoucnosti. S jistou mírou spolehlivosti je možno konstatovat, že cílené vyšetřování a eradikace Helicobacter pylori snižuje incidenci a mortalitu karcinomu žaludku asijské populace. Tato zjištění dosud nelze beze zbytku aplikovat na populaci evropskou nebo americkou. Indikace eradikace Helicobacter pylori musí být zvažována uvážlivě, v souladu s principy personalizované medicíny.
Helicobacter pylori belongs to the most common bacterial infections worldwide; despite its decreasing prevalence during the past four decades (currently ~ 40–50%), it is more prevalent in developing countries compared to developed ones. Intensive research of chronic Helicobacter pylori infection clarified the pathogenesis of several gastric and extragastric diseases, including different cancers. This review pointed out the role of Helicobacter pylori in different gastric malignancies. Chronic Helicobacter pylori infection is an etiological factor in non--cardia gastric cancer and most cases of low-grade MALT lymphoma of the stomach. However, there is an inverse association of Helicobacter pylori infection with other gastric malignancies, like cardia gastric cancer or rare hereditary Gastric Adenocarcinoma and Proximal Polyposis of the Stomach syndrome (GAPPS). A crucial issue has not been definitely solved yet: whether early eradication of Helicobacter pylori could prevent sporadic gastric cancer in the future? There is moderate evidence that searching for and eradicating Helicobacter pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, although data cannot necessarily be extrapolated to European or US populations so far. Indication for the eradication of Helicobacter pylori must now be considered with caution, on an individual basis of personalized medicine.
- MeSH
- Helicobacter pylori * pathogenicity MeSH
- Helicobacter Infections epidemiology drug therapy complications MeSH
- Humans MeSH
- Lymphoma, B-Cell, Marginal Zone etiology pathology MeSH
- Stomach Neoplasms * etiology pathology prevention & control MeSH
- Risk Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Gram-positive bacteria are responsible for a wide range of infections in humans. In most Gram-positive bacteria, sortase A plays a significant role in attaching virulence factors to the bacteria's cell wall. These cell surface proteins play a significant role in virulence and pathogenesis. Even though antibiotics are available to treat these infections, there is a continuous search for an alternative strategy due to an increase in antibiotic resistance. Thus, using anti-sortase drugs to combat these bacterial infections may be a promising approach. Here, we describe a method for targeting Gram-positive bacterial infection by combining curcumin and trans-chalcone as sortase A inhibitors. We have used curcumin and trans-chalcone alone and in combination as a sortase A inhibitor. We have seen ~78%, ~43%, and ~94% inhibition when treated with curcumin, trans-chalcone, and a combination of both compounds, respectively. The compounds have also shown a significant effect on biofilm formation, IgG binding, protein A recruitment, and IgG deposition. We discovered that combining curcumin and trans-chalcone is more effective against Gram-positive bacteria than either compound alone. The present work demonstrated that a combination of these natural compounds could be used as an antivirulence therapy against Gram-positive bacterial infection.
- MeSH
- Aminoacyltransferases * antagonists & inhibitors metabolism MeSH
- Anti-Bacterial Agents * pharmacology chemistry MeSH
- Bacterial Proteins * metabolism antagonists & inhibitors MeSH
- Biofilms * drug effects MeSH
- Chalcone * pharmacology chemistry MeSH
- Cysteine Endopeptidases * metabolism MeSH
- Virulence Factors metabolism MeSH
- Gram-Positive Bacterial Infections drug therapy microbiology MeSH
- Gram-Positive Bacteria drug effects MeSH
- Curcumin * pharmacology chemistry MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Virulence drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. METHODS: In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. FINDINGS: We screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. INTERPRETATION: Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. FUNDING: US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.
- MeSH
- Bacterial Vaccines immunology administration & dosage MeSH
- Adult MeSH
- Phylogeny MeSH
- Genetic Variation genetics MeSH
- Genome, Bacterial MeSH
- Genomics MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Molecular Epidemiology * MeSH
- Cross-Sectional Studies MeSH
- Whole Genome Sequencing * MeSH
- Syphilis * epidemiology microbiology MeSH
- Treponema pallidum * genetics immunology MeSH
- Treponema MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- United States MeSH
BACKGROUND: Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. METHODS: In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. RESULTS: AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. CONCLUSION: Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Antigens, Bacterial * metabolism MeSH
- Bacterial Proteins * metabolism MeSH
- Cell Line MeSH
- Epithelial Cells microbiology MeSH
- Virulence Factors metabolism MeSH
- Helicobacter pylori * drug effects MeSH
- Helicobacter Infections * microbiology drug therapy MeSH
- Host-Pathogen Interactions MeSH
- Metal Nanoparticles * MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Signal Transduction * drug effects MeSH
- Silver * pharmacology metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Súhrn: Hidradenitis suppurativa (HS) je chronický imunitne mediovaný zápal pilosebaceóznej jednotky a apokrinných potných žliaz s tvorbou bolestivých uzlov, abscesov, hnisajúcich fistúl a jaziev predilekčne v intertiginóznych priestoroch. U pacientov s HS je zvýšená incidencia zápalových ochorení čreva (IBD – inflammatory bowel disease), čo poukazuje na ich vzájomné priesečníky v patogenéze dysregulácie vrodenej a adaptívnej imunity. Nedávno sa výrazne zvýšil záujem o črevný mikrobióm kožných ochorení, predmetom záujmu je aj jeho úloha v patogenéze HS. Podľa literárnych údajov črevná dysbióza podporuje produkciu prozápalových cytokínov a následne tvorbu HS lézií. Syndróm prerastania baktérií v tenkom čreve (SIBO – small intestinal bacterial overgrowth) je stav, ktorý sa vyznačuje zvýšenou koncentráciou baktérií hrubého čreva v tenkom čreve. Eredikácia SIBO bola napr. schopná zlepšiť kožné prejavy pri psoriáze, v zmysle zníženia indexu jej závažnosti. V tomto kontexte existuje hypotéza, že eredikácia SIBO môže mať priaznivý vplyv na závažnosť prejavov zápalových imunitne mediovaných kožných ochorení, vrátane HS.
Hidradenitis suppurativa (HS) is a chronic immune-mediated inflammatory skin disease. It is characterized by an inflammation that affects apocrine gland bearing skin in axillae, groin and under the breasts with the formation of painful nodules, abscesses and purulent discharge, sinuses and scaring. Patients with HS have an increased incidence of inflammatory bowel disease (IBD), which also indicates their cross-sections in the pathogenesis of dysregulation congenital and adaptive immunity. Recently, there has been a significant increase of interest in the intestinal microbiome and skin disease, as much as its role in the pathogenesis of HS. According to literature, intestinal dysbiosis promotes the production of proinflammatory cytokines and consequently the formation of HS lesions. Overgrowth of bacteria in the small intestine (SIBO) is a condition characterized by an increased concentration of bacteria in the large intestine. Eradication of SIBO was able to improve psoriasis measured by the psoriasis severity index. In this context, it is hypothesized that eredication of SIBO may have a beneficial effect on the severity of manifestations in inflammatory immune-mediated skin diseases, including HS.
This research paper presents a novel approach to the green synthesis of silver nanoparticles (AgNPs) using viticultural waste, allowing to obtain NP dispersions with distinct properties and morphologies (monodisperse and polydisperse AgNPs, referred to as mAgNPs and pAgNPs) and to compare their biological activities. Our synthesis method utilized the ethanolic extract of Vitis vinifera pruning residues, resulting in the production of mAgNPs and pAgNPs with average sizes of 12 ± 5 nm and 19 ± 14 nm, respectively. Both these AgNPs preparations demonstrated an exceptional stability in terms of size distribution, which was maintained for one year. Antimicrobial testing revealed that both types of AgNPs inhibited either the growth of planktonic cells or the metabolic activity of biofilm sessile cells in Gram-negative bacteria and yeasts. No comparable activity was found towards Gram-positives. Overall, pAgNPs exhibited a higher antimicrobial efficacy compared to their monodisperse counterparts, suggesting that their size and shape may provide a broader spectrum of interactions with target cells. Both AgNP preparations showed no cytotoxicity towards a human keratinocyte cell line. Furthermore, in vivo tests using a silkworm animal model indicated the biocompatibility of the phytosynthesized AgNPs, as they had no adverse effects on insect larvae viability. These findings emphasize the potential of targeted AgNPs synthesized from viticultural waste as environmentally friendly antimicrobial agents with minimal impact on higher organisms.
- MeSH
- Anti-Infective Agents pharmacology chemistry MeSH
- Biofilms drug effects MeSH
- Bombyx MeSH
- Cell Line MeSH
- Gram-Negative Bacteria drug effects MeSH
- Keratinocytes drug effects MeSH
- Metal Nanoparticles * chemistry MeSH
- Yeasts drug effects MeSH
- Larva drug effects MeSH
- Humans MeSH
- Microbial Sensitivity Tests * MeSH
- Plant Extracts pharmacology chemistry MeSH
- Silver * pharmacology chemistry metabolism MeSH
- Green Chemistry Technology MeSH
- Particle Size MeSH
- Cell Survival drug effects MeSH
- Vitis * chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Tellurite resistance gene clusters have been identified in numerous pathogenic bacteria, including clinical isolates of Escherichia coli. The rareness of tellurium in host organisms and the noncontaminated environment raises a question about the true functionality of tellurite resistance gene clusters in pathogenesis and their possible contribution to bacterial fitness. The study aims to point out the beneficial effects of the tellurite resistance gene cluster of pathogenic bacteria to survive in ROS-rich environments. Here, we analysed the bacterial response to oxidative stress conditions with and without tellurite resistance gene clusters, which are composed of terWY1XY2Y3 and terZABCDEF genes. By measuring the levels of protein carbonylation, lipid peroxidation, and expression changes of oxidative stress genes upon oxidative stress, we propose a tellurite resistance gene cluster contribution to the elimination of oxidative damage, potentially increasing fitness and resistance to reactive oxygen species during macrophage attack. We have shown a different beneficial effect of various truncated versions of the tellurite resistance gene cluster on cell survival. The terBCDEF genes increased the survival of E. coli strain MC4100 by 13.21%, terW and terZABCDEF by 10.09%, and terWY1XY2Y3 and terZABCDEF by 25.57%, respectively. The ability to survive tellurite treatment is the most significant at 44.8% in wild clinical strain KL53 compared to laboratory strain E. coli MC4100 due to a complete wild-type plasmid presence.
- MeSH
- Escherichia coli * MeSH
- Multigene Family MeSH
- Oxidative Stress MeSH
- Tellurium * pharmacology metabolism MeSH
- Publication type
- Journal Article MeSH
