RESUMEN
The Ames test is used worldwide to initially screen the mutagenic potential of new chemicals. In the standard Ames test, S. typhimurium strains (TA100, TA98, TA1535, and TA1537) and Escherichia coli (WP2uvrA) are treated with substances with/without cytochrome P450s (CYPs)-induced rat S9 fractions for identifying mutagens and pro-mutagens. However, many substances show completely different toxicity patterns depending on whether the liver S9 fraction belongs to rats or humans. The natural product Polygoni Multiflori Radix (PMR) can also show bacterial reverse mutation, followed by the rat or human liver S9 fraction. While PMR elicits reverse mutations in the TA1537 strain in rat liver S9 but not in human liver S9, this mechanism has not been verified yet. To explain this, the differences in metabolic enzymes compositions commonly observed between rats and humans have been implicated. This study aimed to explore the key factors that cause differences in the genotoxicity of PMR between rat and human liver S9 metabolic enzymes. The results of next-generation sequencing (NGS) analysis showed that both rat and human metabolic enzymes caused similar mutations in TA1537. However, when the metabolic enzymes in each S9 fraction were analyzed using ion mobility tandem mass spectrometry (IM-MS), rat- and human-specific enzymes were identified among the cytochrome (CYP) family, especially aryl hydrocarbon receptor (AHR)-related CYPs. These findings suggest that CYP1A1 isoforms contribute to the mechanism of PMR in the Ames test. Therefore, an in vitro Ames test might be more reliable in predicting genotoxicity for both rodents and humans. This will also help overcome the limitations of laboratory animal-based toxicity evaluations, which provide unreliable results due to interspecies differences between humans and rodents.
Asunto(s)
Pruebas de Mutagenicidad , Mutágenos , Salmonella typhimurium , Animales , Humanos , Pruebas de Mutagenicidad/métodos , Ratas , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Mutágenos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Activación Metabólica , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Mutación , Daño del ADN/efectos de los fármacos , Fallopia multiflora/química , MasculinoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Abutilon indicum, a shrub of the Malvaceae family, is found abundantly in tropical countries like India. A. indicum is widely used for its high medicinal properties. Traditionally, A. indicum seed powder is consumed to treat piles, constipation, chronic cystitis, gonorrhea, gleet, and pregnancy-related problems. Despite having numerous medicinal properties and widespread traditional use of A. indicum seeds, scientific validation, and toxicity studies have yet to be documented. AIMS OF THE STUDY: The primary objective of this study is to conduct a comprehensive study on phytochemical profiling, in-vitro cytotoxicity, mutagenicity, and in-vivo acute and sub-acute toxicity, and genotoxicity on animal models of methanolic extract of A. indicum seed (MAS). MATERIALS AND METHODS: The qualitative analysis of MAS was explored through FTIR and HR LC-MS. For in-vitro cytotoxicity, the HEK-293 cell line was used, and the TA100 (Staphylococcus typhimurium) bacterial strain was used for the Ames mutagenicity test. A single oral dose of 250, 500, 1000, or 2000 mg/kg body weight of MAS was given to each male and female rat for acute toxicity study and observed for 14 days for any toxicity signs. In the sub-acute toxicity study, 250, 500, or 1000 mg/kg body weight of MAS was administered orally to each rat for 28 days. The experimental animals were weighed weekly, and general behavior was monitored regularly. After 28 days of the experiment, the rats were sacrificed, and different serum biochemical, hematological, and histological analyses were performed. The blood samples of different doses of MAS were used for genotoxicity study through comet assay. RESULTS: FTIR analysis found different functional groups, which indicated the presence of phenolics, flavonoids, and alkaloids. HR LC-MS analysis depicts several components with different biological functions. The cell cytotoxicity and Ames mutagenicity results showed minimal toxicity and mutagenicity up to a certain dose. The acute toxicity study conducted in Wistar albino rats demonstrated zero mortality among the animals, and the LD50 value for seed extract was determined to be 2000 mg/kg body weight. Sub-acute toxicity assessments indicated that the administration of seed extract resulted in no adverse effects at dosages of 250 and 500 mg/kg body weight. However, at higher doses, specifically 1000 mg/kg body weight, the liver of the experimental rats exhibited some toxic effects. In the genotoxicity study, minimal DNA damage was found in 250 and 500 mg/kg doses, respectively, but slightly greater DNA damage was found in 1000 mg/kg doses in both male and female rats. CONCLUSIONS: The consumption of A. indicum seed powder is deemed safe; however, doses exceeding 500 mg/kg body weight may raise concerns regarding use. These findings pave the path for the creation of innovative medicines with improved efficacy and safety profiles.
Asunto(s)
Malvaceae , Pruebas de Mutagenicidad , Extractos Vegetales , Semillas , Animales , Extractos Vegetales/toxicidad , Extractos Vegetales/administración & dosificación , Femenino , Semillas/química , Masculino , Humanos , Ratas , Células HEK293 , Malvaceae/química , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Metanol/química , Pruebas de Toxicidad Aguda , Relación Dosis-Respuesta a Droga , Supervivencia Celular/efectos de los fármacos , Ratas Wistar , Ratas Sprague-DawleyRESUMEN
Garviecin LG34 produced by Lactococcus garvieae LG34 exhibits wide-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. This work aimed at clarifying the antibacterial mode of action of garviecin LG34 against Gram-negative bacterium Salmonella typhimurium. To determine the concentration for the bacteriocin antimicrobial mode experiments, the minimum inhibitory concentration of garviecin LG34 against S. typhimurium CICC21484 was determined as 0.25 mg/ml. Garviecin LG34 decreased the viable count of S. typhimurium CICC21484 and its antibacterial activity was the dose and time dependant. Garviecin LG34 led to the dissipation of transmembrane potential, the rise in the extracellular conductivity, UV-absorbing material at 260 nm, and LDH level of S. typhimurium CICC21484. Scanning electron micrographs results shown that garviecin LG34 cause dramatic deformation and fragmentation including the flagellum shedding, pores formation in surface, and even completely breakage of S. typhimurium cell. Moreover, garviecin LG34 decreased the intracellular ATP level. The results of this study demonstrated that garviecin LG34 can destroy cell structure, increase membrane permeability of S. typhimurium, thereby might be used as biopreservative for treating food borne and salmonellosis resulting from Gram-negative bacterium S. typhimurium.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Salmonella typhimurium , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Antibacterianos/farmacología , Antibacterianos/química , Bacteriocinas/farmacología , Lactococcus/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Potenciales de la Membrana/efectos de los fármacosRESUMEN
Synergistic combinations of immunotherapeutic agents can improve the performance of anti-cancer therapies but may lead to immune-mediated adverse effects. These side-effects can be overcome by using a tumor-specific delivery system. Here, we report a method of targeted immunotherapy using an attenuated Salmonella typhimurium (SAM-FC) engineered to release dual payloads: cytolysin A (ClyA), a cytolytic anti-cancer agent, and Vibrio vulnificus flagellin B (FlaB), a potent inducer of anti-tumor innate immunity. Localized secretion of ClyA from SAM-FC induces immunogenic cancer cell death and promotes release of tumor-specific antigens and damage-associated molecular patterns, which establish long-term antitumor memory. Localized secretion of FlaB promotes phenotypic and functional remodeling of intratumoral macrophages that markedly inhibits tumor metastasis in mice bearing tumors of mouse and human origin. Both primary and metastatic tumors from bacteria-treated female mice are characterized by massive infiltration of anti-tumorigenic innate immune cells and activated tumor-specific effector/memory T cells; however, the percentage of immunosuppressive cells is low. Here, we show that SAM-FC induces functional reprogramming of the tumor immune microenvironment by activating both the innate and adaptive arms of the immune system and can be used for targeted delivery of multiple immunotherapeutic payloads for the establishment of potent and long-lasting antitumor immunity.
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Inmunoterapia , Salmonella typhimurium , Microambiente Tumoral , Animales , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Salmonella typhimurium/inmunología , Salmonella typhimurium/efectos de los fármacos , Femenino , Ratones , Humanos , Inmunoterapia/métodos , Línea Celular Tumoral , Inmunidad Innata/efectos de los fármacos , Ratones Endogámicos C57BL , Flagelina/inmunología , Vibrio vulnificus/inmunología , Vibrio vulnificus/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificaciónRESUMEN
In the present study, the effects of levamlodipine benzenesulfonate on the development of fertile Sprague-Dawley (SD) rats, their embryos, and littermates were assessed using an embryo-fetal developmental toxicity test. Maternal body weight reduction was observed at a dose of 20â¯mg/kg, but it recovered after treatment cessation. The 20â¯mg/kg dose group showed a skewed sex ratio in fetal rats, with a higher proportion of males. While some effects on fetal sternum development were observed at 20â¯mg/kg, no skeletal malformations were observed. No significant gross morphological abnormalities were detected in the dams (mothers), no significant embryotoxicity or foetotoxicity in fetal rats and no significant effects on fetal length and weight development at doses of 5 and 10â¯mg/kg. Genotoxicity was evaluated using a combination of the Ames test, the Chinese hamster ovary (CHO) cell chromosome aberration assay, and the ICR mouse bone marrow micronucleus test. The Ames test results indicated substantial bacteriostatic effects at doses of 500 and 5000â¯mg/dish, with no mutagenicity observed at doses of 0.5, 5, and 50â¯mg/dish. No significant effect on the aberration rate of CHO cell chromosomes was found at doses of 2.8, 5.6, and 11.2â¯mg/mL. In the ICR mouse micronucleus test, no micronucleus-inducing effect was observed at doses of 3.125, 6.25, and 12.5â¯mg/kg in each treatment group. In conclusion, under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for developmental toxicity of levamlodipine benzenesulfonate in fertile SD rats, their embryos, and littermates was established to be 10â¯mg/kg/day. Levamlodipine benzenesulfonate did not exhibit significant genotoxicity.
Asunto(s)
Aberraciones Cromosómicas , Cricetulus , Pruebas de Mutagenicidad , Ratas Sprague-Dawley , Animales , Femenino , Masculino , Células CHO , Ratas , Cricetinae , Ratones , Embarazo , Aberraciones Cromosómicas/inducido químicamente , Ratones Endogámicos ICR , Pruebas de Micronúcleos , Relación Dosis-Respuesta a Droga , Desarrollo Embrionario/efectos de los fármacos , Desarrollo Fetal/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Razón de Masculinidad , Peso Corporal/efectos de los fármacos , Mutágenos/toxicidadRESUMEN
Biofilm formation in natural environments involving complex multi-structural arrangements hinders challenges in antimicrobial resistance. This study investigated the antimicrobial resistance potential of grapefruit seed extract (GSE) by examining the formation of mono-, dual-, and multi-species biofilms. We also explored the counterintuitive effect in response to GSE at various concentrations, including minimum inhibitory concentration (MIC) and sub-MIC (1/2 and 1/4 MIC). The results of the swimming and swarming motility tests revealed increased motility at the sub-MIC of GSE. The crystal violet assay demonstrated increased biofilm formation in multi-species biofilms, highlighting the synergistic effect of Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes. At the MIC concentration of GSE, field emission scanning electron microscopy (FE-SEM) revealed cell morphology damage, while sub-MIC increased biofilm formation and architectural complexity. Multi-species biofilms demonstrated greater biofilm-forming ability and antimicrobial resistance than mono-species biofilms, indicating synergistic interactions and enhanced resilience. These findings highlight the importance of understanding biofilm dynamics and antimicrobial resistance to ensure environmental safety.
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Antibacterianos , Biopelículas , Citrus paradisi , Escherichia coli , Listeria monocytogenes , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Semillas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Listeria monocytogenes/fisiología , Farmacorresistencia Bacteriana , Microbiología de Alimentos , Salmonella typhimurium/efectos de los fármacosRESUMEN
Phillyrin is extracted from Forsythia suspensa (Thunb.) Vahl, is significantly higher in (unripe Forsythiae Fructus) Qing qiao than in (ripe Forsythiae Fructus) Lao qiao fruits of the plant. However, the toxicity of phillyrin has not been adequately investigated. The study investigates the genetic and teratogenic effects of phillyrin to determine its safety profile. Assessing the genotoxicity and teratogenicity of phillyrin involved various tests, such as the bacterial reverse mutation assay, mammalian erythrocyte micronucleus assay, spermatocyte chromosome aberration assay, and teratogenicity assay. The results demonstrated that phillyrin exhibited no discernible impact on the following: number of colonies that spontaneously revert for Salmonella typhimurium TA 97, TA98, TA100, TA102, and TA1535, frequency of bone marrow polychromatic erythrocytes, and the rate of chromosomal aberrations. In the teratogenicity test, the pregnant rats exhibited no signs of toxicity or abnormal changes, and the growth, embryonic development, and visual anatomy of each pup were normal. In comparison with the negative control group, there were no significant differences in fetal body weight, mortality, deformity rate, malformed nest rate, gravid uterus weight, average number of fetuses per litter, fetal body length, or visceral and skeletal development in each dose group. In conclusion, these findings provide evidence that phillyrin does not exhibit genotoxic or teratogenic effects, supporting its potential safety for pharmacological applications.
Asunto(s)
Aberraciones Cromosómicas , Pruebas de Mutagenicidad , Teratógenos , Animales , Femenino , Masculino , Teratógenos/toxicidad , Ratas , Aberraciones Cromosómicas/inducido químicamente , Ratones , Pruebas de Micronúcleos , Embarazo , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , GlucósidosRESUMEN
Using a solvent-casting method, a poly(lactic acid) (PLA) film incorporated with caprylic acid (CA) was developed as an active packaging against Salmonella enterica ser. Typhimurium and S. enteritidis to reduce the risk of microbial contamination during distribution and storage of meat. According to the minimum inhibitory concentration (MIC) test results of the natural antimicrobial, CA was introduced at 0.6, 1.2, 2.4, and 4.8 % (v/v) into neat PLA. The biofilm inhibitory effect and antimicrobial efficacy of CA-PLA film against both Salmonella strains, as well as the intermolecular interactions and barrier properties of CA-PLA film, were evaluated. Biofilm formation was reduced to below the detection limit (<1.0 log CFU/cm2) for both S. typhimurium and S. enteritidis when co-cultured overnight with 4.8 % CA-PLA film. The 4.8 % CA-PLA film achieved maximum log reductions of 2.58 and 1.65 CFU/g for S. typhimurium and 2.59 and 1.76 CFU/g for S. enteritidis on inoculated chicken breast and beef stored at 25 °C overnight, respectively, without any quality (color and texture) losses. CA maintained its typical chemical structure in the film, as confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra. Furthermore, film surface morphology observations by field emission scanning electron microscopy (FESEM) showed that CA-PLA film was smoother than neat PLA film. No significant (P > 0.05) changes were observed for water vapor permeability and oxygen permeability by the addition of CA into PLA film, suggesting that CA-PLA film is a promising strategy for active packaging to control Salmonella contamination in the meat industry.
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Biopelículas , Caprilatos , Embalaje de Alimentos , Carne , Pruebas de Sensibilidad Microbiana , Poliésteres , Salmonella typhimurium , Caprilatos/farmacología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Embalaje de Alimentos/métodos , Poliésteres/farmacología , Poliésteres/química , Carne/microbiología , Animales , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Bovinos , Pollos , Salmonella enteritidis/efectos de los fármacos , Salmonella enteritidis/crecimiento & desarrollo , Microbiología de Alimentos , Contaminación de Alimentos/prevención & control , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Salmonella/efectos de los fármacos , Salmonella/crecimiento & desarrollo , Polímeros/farmacología , Polímeros/química , Ácido Láctico/farmacologíaRESUMEN
In Salmonella enterica serovar Typhimurium (Typhimurium), multidrug resistance is associated with integrons carrying resistance genes dispersed by mobile genetic elements. This exploratory systematic review sought to identify integron types and their resistance genes in multidrug resistance Typhimurium isolates. We used Medline, PubMed, SciELO, ScienceDirect, Redalyc, and Google Scholar as motor searchers for articles in Spanish or English published between 2012 and 2020, including the keywords "integrons", "antibiotic resistance", and "Salmonella Typhimurium". We included 38 articles reporting multidrug resistance up to five antibiotic families. Class 1 integrons with aadA2 and blaPSE-1 gene cassettes were predominant, some probably related to the Salmonella genomic island 1. We did not find studies detailing class 1 and 2 integrons in the same isolate, nor class 3 integrons reported. The presence of integrons largely explains the resistance profiles found in isolates from different sources in 15 countries.
La multirresistencia a los antibióticos en Salmonella enterica serovar Typhimurium (Typhimurium) se asocia con integrones que portan genes de resistencia y que son dispersados por elementos genéticos móviles. En esta revisión sistemática exploratoria, se buscó identificar los tipos de integrones y sus genes de resistencia en aislamientos de Typhimurium multirresistentes a antibióticos. Se realizó una búsqueda de artículos en Medline, PubMed, SciELO, ScienceDirect, Redalyc y Google Académico, publicados entre el 2012 y el 2020, en español o inglés, con las palabras claves: "integrons", "antibiotic resistance" y "Salmonella Typhimurium". En el análisis se incluyeron 38 artículos que reportaron multirresistencia a cinco familias de antibióticos. Los integrones de clase 1 con casetes de genes aadA2 y blaPSE-1 fueron los predominantes, algunos probablemente relacionados con la isla genómica de Salmonella 1. No se encontraron integrones de clase 1 y 2 en un mismo aislamiento, ni se reportaron integrones de clase 3. La presencia de integrones explica en gran medida los perfiles de resistencia encontrados en aislamientos de diferentes fuentes de 15 países.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Integrones , Salmonella typhimurium , Integrones/genética , Farmacorresistencia Bacteriana Múltiple/genética , Salmonella typhimurium/genética , Salmonella typhimurium/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/epidemiología , Islas Genómicas , AnimalesRESUMEN
The aim of this study was to characterize the pulp of Rheum ribes L. and to determine the effect of the pulp enriched with eugenol (1 %) or thymol (1 %) on the microbiological and physico-chemical quality of chicken breast fillets. Chicken breast fillets, inoculated with Listeria monocytogenes, Salmonella enterica subsp. enterica serovar Typhimurium, and Escherichia coli O157:H7 (~6.0 log10), were marinated for 24 h in a mixture prepared from a combination of Rheum ribes L. pulp with eugenol or thymol. The quality parameters were analyzed for 15 days at +4 °C. The Rheum ribes L. pulp was found to have high antioxidant activity, high total phenolic content and contained 22 different phenolic substances, among which rutin ranked first. The pulp contained high levels of p-xylene and o-xylene as volatile substances and citric acid as an organic acid. The combination of Pulp + Eugenol + Thymol (PET) reduced the number of pathogens in chicken breast fillets by 2.03 to 3.50 log10 on day 0 and by 2.25 to 4.21 log10 on day 15, compared to the control group (P < 0.05). The marinating treatment significantly lowered the pH values of fillet samples on the first day of the study, compared to the control group (P < 0.05). During storage, TVB-N levels showed slower increase in the treatment groups compared to the control group (P < 0.05). In addition, the marinating process led to significant changes in physicochemical parameters such as water holding capacity, color, texture, cooking loss, and drip loss compared to the control group (P < 0.05). In conclusion, the results of this study showed that the pulp of Rheum ribes L., which has a high antioxidant capacity and contains various bioactive compounds. Furthermore, S. Typhimurium, E. coli O157:H7 and L. monocytogenes were inhibited considerably by marinating Rheum ribes L. pulp with a combination of eugenol and thymol.
Asunto(s)
Pollos , Eugenol , Rheum , Timol , Animales , Timol/farmacología , Eugenol/farmacología , Rheum/química , Conservación de Alimentos/métodos , Microbiología de Alimentos , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Carne/microbiología , Escherichia coli O157/efectos de los fármacos , Escherichia coli O157/crecimiento & desarrollo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Recuento de Colonia MicrobianaRESUMEN
In the present study, we investigated the genotoxicity of the active products formed from N-nitrosoproline (NPRO) dissolved in oleic acid following ultraviolet A (UVA) irradiation, bypassing the need for metabolic activation. We previously demonstrated the photomutagenicity of NPRO dissolved in a phosphate-buffered solution. It has been suggested that the association of the nitrosamine group with acid ions facilitates rapid photodissociation and photoactivation. We hypothesized that NPRO's inherent carboxyl group may mimic an acid, inducing photodissociation and photomutagenicity, even in a non-aqueous solvent lacking acidic ions. Following UVA irradiation, NPRO dissolved in oleic acid exhibited a dose-dependent mutagenic activity. Similar results were obtained when NPRO was dissolved in linoleic acid and triolein. Nitric oxide formation, which is dependent on NPRO concentration, is accompanied by mutagenic activity. The mutagenicity spectrum obtained in response to NPRO irradiation followed the absorption curve of NPRO dissolved in oleic acid. Irradiated NPRO in oleic acid displayed relative stability, retaining approximately 18, 36, and 63 % of initial mutagenicity after 10 days of storage at 25, 4, and -20 °C, respectively. Thus NPRO stored in a fatty environment undergoes photoactivation upon irradiation, leading to genotoxicity.
Asunto(s)
Pruebas de Mutagenicidad , Ácido Oléico , Solventes , Rayos Ultravioleta , Ácido Oléico/química , Solventes/química , Mutágenos/química , Mutágenos/toxicidad , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/efectos de la radiaciónRESUMEN
In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1â¯mg per plate), with or without metabolic activation, were negative. The micronucleus test with TK6 (human lymphoblastoid) cells, at doses up to 500 µg/mL, with or without metabolic activation, also gave negative results.
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Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Tiroxina , Humanos , Pruebas de Micronúcleos/métodos , Pruebas de Mutagenicidad/métodos , Contaminación de Medicamentos , Mutágenos/toxicidad , Línea Celular , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
This study aimed to evaluate the effects of Euryale ferox Seed Shell Polyphenol Extract (EFSSPE) on a foodborne pathogenic bacterium. EFSSPE showed antimicrobial activity toward Salmonella Typhimurium CICC 22956; the minimum inhibitory concentration of EFSSPE was 1.25 mg/mL, the inhibition curve also reflected the inhibitory effect of EFSSPE on the growth of S. Typhimurium. Detection of alkaline phosphatase outside the cell revealed that EFSSPE treatment damaged the cell wall integrity of S. Typhimurium. EFSSPE also altered the membrane integrity, thereby causing leaching of 260-nm-absorbing material (bacterial proteins and DNA). Moreover, the activities of succinate dehydrogenase and malate dehydrogenase were inhibited by EFSSPE. The hydrophobicity and clustering ability of cells were affected by EFSSPE. Scanning electron microscopy showed that EFSSPE treatment damaged the morphology of the tested bacteria. These results indicate that EFSSPE can destroy the cell wall integrity and alter the permeability of the cell membrane of S. Typhimurium.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Polifenoles , Salmonella typhimurium , Semillas , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Semillas/química , Polifenoles/farmacología , Pared Celular/efectos de los fármacos , Succinato Deshidrogenasa/metabolismo , Succinato Deshidrogenasa/antagonistas & inhibidores , Microscopía Electrónica de Rastreo , Malato Deshidrogenasa/metabolismo , Proteínas Bacterianas/metabolismo , Membrana Celular/efectos de los fármacos , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
This study aimed to understand the epidemiological characteristics of Salmonella in Tibetan pigs. We isolated, identified, and examined via antimicrobial susceptibility testing on Salmonella from Tibetan pigs breeder farms and slaughterhouses in Tibet, China. A genetic evolutionary tree was constructed on the basis of whole genome sequencing (WGS). A total of 81 Salmonella isolates were isolated from 987 samples. The main serovars were Salmonella Typhimurium and Salmonella London in Tibetan pigs. The isolated Salmonella Typhimurium isolates subjected to antimicrobial susceptibility testing showed varying degrees of resistance to ß-lactams, aminoglycosides, fluoroquinolones, sulfonamides, tetracyclines, and amphenicols. WGS analysis was performed on 20 Salmonella Typhimurium isolates in Tibet (n = 10), Jiangsu (n = 10), and 205 genome sequences downloaded from the Enterobase database to reveal their epidemiological and genetic characteristics. They were divided into two clusters based on core genome single-nucleotide polymorphisms: Cluster A with 112 isolates from Tibet and other regions in China and Cluster B with 113 isolates from Jiangsu and other regions. The isolates in Cluster A were further divided into two subclusters: A-1 with 40 isolates including Tibet and A-2 with 72 isolates from other regions. Virulence factors analysis revealed that all isolates from Tibet carried adeG, but this observation was not as common in Salmonella isolates from Jiangsu and other regions of China. Antibiotic resistance genes (ARGs) analysis showed that all isolates from Tibet carried blaTEM-55 and rmtB, which were absent in Salmonella isolates from Jiangsu and other regions of China. Genetic characteristic analysis and biofilm determination indicated that the biofilm formation capabilities of the isolates from Tibet were stronger than those of the isolates from Jiangsu and other regions of China. Our research revealed the epidemic patterns and genomic characteristics of Salmonella in Tibetan pigs and provided theoretical guidance for the prevention and control of local salmonellosis.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Salmonelosis Animal , Salmonella , Enfermedades de los Porcinos , Animales , Porcinos , Tibet/epidemiología , Salmonelosis Animal/epidemiología , Salmonelosis Animal/microbiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/epidemiología , Prevalencia , Salmonella/genética , Salmonella/aislamiento & purificación , Salmonella/efectos de los fármacos , Salmonella/clasificación , Antibacterianos/farmacología , Secuenciación Completa del Genoma , Factores de Virulencia/genética , Filogenia , Salmonella typhimurium/genética , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple/genética , Polimorfismo de Nucleótido Simple , Genoma BacterianoRESUMEN
The gut microbiota is essential for providing colonization resistance against pathogens. Dietary sugars markedly shift the composition of the intestinal microbiota and alter host susceptibility to enteric infections. Here, we demonstrate the effect of L-arabinose on bacterial infection by using a mouse infection model with Salmonella enterica serovar Typhimurium (S. Tm). In the presence of microbiota, L-arabinose induces a dramatic expansion of Enterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infection. However, L-arabinose supplementation does not alter the disease progression of Salmonella infection in a microbiota-depleted mouse model. More importantly, short-term supplementation of L-arabinose fails to exert anti-diabetic effects in Salmonella-infected hyperglycemia mice and still promotes infection. Overall, our work reveals that a high intake of dietary L-arabinose supports a bloom of Enterobacteriaceae in Salmonella-infected gut, further accelerating the process of systemic infection.IMPORTANCEL-arabinose is a promising natural sweetener and food additive for the regulation of hyperglycemia. Since diabetic subjects are more susceptible to infections, the safety of dietary L-arabinose in diabetic patients experiencing infection remains a concern. Our findings reveal that L-arabinose exacerbates Salmonella infection outcome by inducing gut microbiota dysbiosis in mice. High dietary intake of L-arabinose may be deleterious for diabetic individuals undergoing infection.
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Arabinosa , Disbiosis , Microbioma Gastrointestinal , Infecciones por Salmonella , Salmonella typhimurium , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Disbiosis/microbiología , Arabinosa/farmacología , Ratones , Infecciones por Salmonella/microbiología , Salmonella typhimurium/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Enterobacteriaceae/efectos de los fármacosRESUMEN
Phototherapy utilizing bacterial carriers has demonstrated efficacy in anti-tumor therapy, while the poor delivery of phototherapeutic agents and immunogenicity of microbial substances remain problematic. Herein, we develop a nanocoated bacterial delivery system (IF-S.T) that in situ forms the efficient photothermal agents via biomineralization and improves the intracellular oxygenation, thus triggering the self-enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) on tumor. We densely coat self-assembled IF (ICG-Fe2+) nanocomplex onto the surface of LT2, weakly virulent strain of Salmonella typhimurium (S.T), by bioadaptive nanocoating techniques, masking bacterial virulence factors and reducing the potential immune adverse effects. Upon penetrating into the tumor environment, IF-S.T responds to H2O2 to trigger the removal of the IF coating, where S.T produces excess hydrogen sulfide (H2S). H2S reacts with Fe2+, yielding ferrous sulfide (FeS) for PTT, and inhibits mitochondrial respiration to enhance tumor cell oxygenation for PDT. Consequently, IF-S.T plus laser irradiation exhibits direct tumor cells killing and elicits robust antitumor immune responses, leading to the complete tumor elimination. Thus, IF-S.T represents a promising platform for effective tumor delivery of photoactive agents for improved PTT/PDT efficacy.
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Neoplasias de la Mama , Sulfuro de Hidrógeno , Ratones Endogámicos BALB C , Fotoquimioterapia , Salmonella typhimurium , Animales , Fotoquimioterapia/métodos , Femenino , Sulfuro de Hidrógeno/química , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Salmonella typhimurium/efectos de los fármacos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Verde de Indocianina/administración & dosificación , Humanos , Terapia Fototérmica/métodos , Ratones , Peróxido de Hidrógeno , Fototerapia/métodosRESUMEN
Humans and animals encounter a summation of exposures during their lifetime (the exposome). In recent years, the scope of the exposome has begun to include microplastics. Microplastics (MPs) have increasingly been found in locations, including in animal gastrointestinal tracts, where there could be an interaction with Salmonella enterica serovar Typhimurium, one of the commonly isolated serovars from processed chicken. However, there is limited knowledge on how gut microbiomes are affected by microplastics and if an effect would be exacerbated by the presence of a pathogen. In this study, we aimed to determine if acute exposure to microplastics in vitro altered the gut microbiome membership and activity. The microbiota response to a 24 h co-exposure to Salmonella enterica serovar Typhimurium and/or low-density polyethylene (PE) microplastics in an in vitro broiler cecal model was determined using 16S rRNA amplicon sequencing (Illumina) and untargeted metabolomics. Community sequencing results indicated that PE fiber with and without S. Typhimurium yielded a lower Firmicutes/Bacteroides ratio compared with other treatment groups, which is associated with poor gut health, and overall had greater changes to the cecal microbial community composition. However, changes in the total metabolome were primarily driven by the presence of S. Typhimurium. Additionally, the co-exposure to PE fiber and S. Typhimurium caused greater cecal microbial community and metabolome changes than either exposure alone. Our results indicate that polymer shape is an important factor in effects resulting from exposure. It also demonstrates that microplastic-pathogen interactions cause metabolic alterations to the chicken cecal microbiome in an in vitro chicken cecal mesocosm. IMPORTANCE: Researching the exposome, a summation of exposure to one's lifespan, will aid in determining the environmental factors that contribute to disease states. There is an emerging concern that microplastic-pathogen interactions in the gastrointestinal tract of broiler chickens may lead to an increase in Salmonella infection across flocks and eventually increased incidence of human salmonellosis cases. In this research article, we elucidated the effects of acute co-exposure to polyethylene microplastics and Salmonella enterica serovar Typhimurium on the ceca microbial community in vitro. Salmonella presence caused strong shifts in the cecal metabolome but not the microbiome. The inverse was true for polyethylene fiber. Polyethylene powder had almost no effect. The co-exposure had worse effects than either alone. This demonstrates that exposure effects to the gut microbial community are contaminant-specific. When combined, the interactions between exposures exacerbate changes to the gut environment, necessitating future experiments studying low-dose chronic exposure effects with in vivo model systems.
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Ciego , Pollos , Microbioma Gastrointestinal , Metaboloma , Polietileno , Salmonella typhimurium , Animales , Pollos/microbiología , Ciego/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Polietileno/metabolismo , Metaboloma/efectos de los fármacos , Microplásticos , ARN Ribosómico 16S/genética , Salmonelosis Animal/microbiologíaRESUMEN
This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection.
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Heces , Microbioma Gastrointestinal , Probióticos , Destete , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Porcinos , Proyectos Piloto , Probióticos/administración & dosificación , Heces/microbiología , Salmonelosis Animal/microbiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/prevención & control , Lactobacillaceae , Salmonella typhimurium/efectos de los fármacosRESUMEN
Biofilms are highly resistant to disinfectants and antimicrobials and are known as the primary source of food contamination. Salmonella Typhimurium (S. Typhimurium) and Staphylococcus aureus (S. aureus) have an excellent ability to form biofilm. This study aimed to evaluate the antibiofilm activity of ozonated water (O), acetic acid (AA), and lactic acid (LA), individually and sequentially, against biofilms of S. Typhimurium and S. aureus formed on the polystyrene surfaces. The antibiofilm effects of the treatments were evaluated using crystal violet staining and the viable count determination methods. In the staining method, the highest percentage of biofilm mass reduction was induced by successive use of ozonated water and acetic acid (O-AA), which reduced S. aureus biofilm mass by 44.36%. The sequential use of ozonated water and lactic acid (O-LA) could decrease S. Typhimurium biofilm mass by 57.26%. According to the viable count method, the most effective treatment was the sequential use of ozonated water and lactic acid (O-LA), which reduced S. aureus and S. Typhimurium biofilms by 1.76 and 4.06 log, respectively. It was concluded that the sequential use of ozonated water and organic acids can be considered a practical and environmentally friendly approach to control biofilms.
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Ácido Acético , Biopelículas , Ácido Láctico , Salmonella typhimurium , Staphylococcus aureus , Agua , Biopelículas/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Ácido Acético/farmacología , Ácido Láctico/farmacología , Agua/farmacología , Recuento de Colonia Microbiana , Ozono/farmacología , Desinfectantes/farmacologíaRESUMEN
Ciprofloxacin-resistant Salmonella Typhimurium (S. Typhimurium) causes a significant health burden worldwide. A wealth of studies has been published on the contributions of different mechanisms to ciprofloxacin resistance in Salmonella spp. But we still lack a deep understanding of the physiological responses and genetic changes that underlie ciprofloxacin exposure. This study aims to know how phenotypic and genotypic characteristics are impacted by ciprofloxacin exposure, from ciprofloxacin-susceptible to ciprofloxacin-resistant strains in vitro. Here, we investigated the multistep evolution of resistance in replicate populations of S. Typhimurium during 24 days of continuously increasing ciprofloxacin exposure and assessed how ciprofloxacin impacts physiology and genetics. Numerous studies have demonstrated that RamA is a global transcriptional regulator that prominently perturbs the transcriptional landscape of S. Typhimurium, resulting in a ciprofloxacin-resistant phenotype appearing first; the quinolone resistance-determining region mutation site can only be detected later. Comparing the microbial physiological changes and RNA sequencing (RNA-Seq) results of ancestral and selectable mutant strains, the selectable mutant strains had some fitness costs, such as decreased virulence, an increase of biofilm-forming ability, a change of "collateral" sensitivity to other drugs, and inability to utilize galactitol. Importantly, in the ciprofloxacin induced, RamA directly binds and activates the gatR gene responsible for the utilization of galactitol, but RamA deletion strains could not activate gatR. The elevated levels of RamA, which inhibit the galactitol metabolic pathway through the activation of gatR, can lead to a reduction in the growth rate, adhesion, and colonization resistance of S. Typhimurium. This finding is supported by studies conducted in M9 medium as well as in vivo infection models. IMPORTANCE: Treatment of antibiotic resistance can significantly benefit from a deeper understanding of the interactions between drugs and genetics. The physiological responses and genetic mechanisms in antibiotic-exposed bacteria are not well understood. Traditional resistance studies, often retrospective, fail to capture the entire resistance development process and typically exhibit unpredictable dynamics. To explore how clinical isolates of S. Typhimurium respond to ciprofloxacin, we analyzed their adaptive responses. We found that S. Typhimurium RamA-mediated regulation disrupts microbial metabolism under ciprofloxacin exposure, affecting genes in the galactitol metabolic pathways. This disruption facilitates adaptive responses to drug therapy and enhances the efficiency of intracellular survival. A more comprehensive and integrated understanding of these physiological and genetic changes is crucial for improving treatment outcomes.