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1.
Biomedica ; 44(2): 258-276, 2024 May 30.
Article in Spanish | MEDLINE | ID: mdl-39088536

ABSTRACT

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.


Subject(s)
Drug Resistance, Multiple, Bacterial , Integrons , Salmonella typhimurium , Integrons/genetics , Drug Resistance, Multiple, Bacterial/genetics , Salmonella typhimurium/genetics , Salmonella typhimurium/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Genomic Islands , Animals
2.
J Agric Food Chem ; 72(28): 16010-16017, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38965162

ABSTRACT

Maillard reaction products (MRPs) of xylose with phenylalanine and xylose with proline exhibit high antibacterial activity. However, the active antibacterial compounds in MRPs have not yet been identified or isolated. This study aimed to isolate the active compounds in the two antibacterial MRPs. The organic layer of the MRP solution was separated and purified using silica gel chromatography and high-performance liquid chromatography. The chemical structures of the isolated compounds were determined by mass spectrometry and nuclear magnetic resonance spectroscopy. The compounds inhibited the growth of Bacillus cereus and Salmonella Typhimurium at 25 °C for 7 days at a concentration of 0.25 mM. Furthermore, the isolated compounds inhibited the growth of naturally occurring microflora of lettuce and chicken thighs at 25 °C for 2 days at a concentration of 0.5-1.0 mM. The antibacterial compounds found in MRPs demonstrated a wide range of effectiveness and indicated their potential as alternative preservatives.


Subject(s)
Anti-Bacterial Agents , Chickens , Maillard Reaction , Phenylalanine , Proline , Salmonella typhimurium , Xylose , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Proline/chemistry , Phenylalanine/chemistry , Xylose/chemistry , Salmonella typhimurium/drug effects , Animals , Bacillus cereus/drug effects , Bacillus cereus/growth & development , Chromatography, High Pressure Liquid
3.
FEMS Microbiol Lett ; 3712024 Jan 09.
Article in English | MEDLINE | ID: mdl-39012705

ABSTRACT

This study was designed to evaluate the history-dependent behaviors of Salmonella Typhimurium re-exposed to sublethal levels of ciprofloxacin. The S. Typhimurium cells were pre-exposed to 0 (CON), 1/16 (LOW), 1/8 (MED), and 1/4 (HIGH) minimum inhibitory concentrations (MICs) of ciprofloxacin, followed by re-exposure to the same concentrations. The bacterial growth, postantibiotic effect (PAE), relative fitness, and swimming motility of treatments were evaluated in the absence of ciprofloxacin. The lag phase duration (LPD) was estimate to assess bacterial recovery under ciprofloxacin exposure. A disk diffusion assay was used to determine the cross-resistance and collateral sensitivity of CON, LOW, MED, and HIGH treatments to ciprofloxacin (CIP), ceftriaxone (CEF), erythromycin (ERY), gentamicin (GEN), and polymyxin B (POL). The S. Typhimurium cells pre-exposed to ciprofloxacin were susceptible in antibiotic-free media, showing delayed growth. The highest PAE (>1 h) and bacterial fluctuation (CV = 5%) were observed at the High treatment compared to the CON. The HIGH treatment had the lowest relative fitness levels (0.87) and swimming motility (55 mm). The LPD was significantly decreased at the LOW treatment (1.8 h) when re-exposed to 1/16 × MIC of ciprofloxacin. The LOW, MED, and HIGH treatments showed the cross-resistance to POL and the collateral sensitivity to CEF, ERY, and GEN. The pre-exposure to ciprofloxacin could induce phenotypic diversity, corresponding to the history-dependent behaviors. These results provide important insights for the dynamic nature of bacterial populations when re-exposed to sublethal concentrations of antibiotics.


Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Microbial Sensitivity Tests , Salmonella typhimurium , Ciprofloxacin/pharmacology , Salmonella typhimurium/drug effects , Salmonella typhimurium/growth & development , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial
4.
Curr Microbiol ; 81(8): 262, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981879

ABSTRACT

The vast dissemination of resistance to different antibiotics among bacterial pathogens, especially foodborne pathogens, has drawn major research attention. Thus, many attempts have been made to reveal novel alternatives to the current antibiotics. Due to their variable pharmacologically active phytochemicals, plants represent a good solution for this issue. This study investigated the antibacterial potential of Kumquat or Fortunella japonica methanol extract (FJME) against Salmonella typhimurium clinical isolates. Gas chromatography coupled with mass spectrometry (GC/MS) characterized 39 compounds in FJME. Palmitic acid (15.386%) and cis-vaccenic acid (15.012%) are the major active constituents detected by GC/MS. Remarkably, FJME had minimum inhibitory concentrations from 128 to 512 µg/mL in vitro. In addition, a systemic infection model revealed the in vivo antibacterial action of FJME. The antibacterial therapeutic activity of FJME was noticed by improving the histological features of the liver and spleen. Moreover, there was a perceptible lessening (p < 0.05) of the levels of the oxidative stress markers (nitric oxide and malondialdehyde) using ELISA. In addition, the gene expression of the proinflammatory cytokine (interleukin 6) was downregulated. On the other hand, there was an upregulation of the anti-inflammatory cytokine (interleukin 10). Accordingly, future clinical investigations should be done to reveal the potential antibacterial action of FJME on other food pathogens.


Subject(s)
Anti-Bacterial Agents , Fruit , Microbial Sensitivity Tests , Plant Extracts , Salmonella typhimurium , Plant Extracts/pharmacology , Plant Extracts/chemistry , Salmonella typhimurium/drug effects , Anti-Bacterial Agents/pharmacology , Fruit/microbiology , Fruit/chemistry , Animals , Mice , Salmonella Infections/microbiology , Salmonella Infections/drug therapy
5.
Sci Rep ; 14(1): 15466, 2024 07 05.
Article in English | MEDLINE | ID: mdl-38965336

ABSTRACT

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.


Subject(s)
Feces , Gastrointestinal Microbiome , Probiotics , Weaning , Animals , Gastrointestinal Microbiome/drug effects , Swine , Pilot Projects , Probiotics/administration & dosage , Feces/microbiology , Salmonella Infections, Animal/microbiology , Swine Diseases/microbiology , Swine Diseases/prevention & control , Lactobacillaceae , Salmonella typhimurium/drug effects
6.
Mol Biol Rep ; 51(1): 794, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39001999

ABSTRACT

BACKGROUND: Salmonellosis is a widespread zoonotic disease that poses a significant threat to livestock and public health. This study aimed to serotype 20 Salmonella isolates obtained from sixty retail chicken meats, assess Salmonella contamination from eggs, and evaluate antibiotic resistance profiles. METHODS AND RESULTS: Twenty eggs were randomly collected in the new Borg El Arab market. Bacterial isolation was carried out utilizing both traditional culture, biochemical, and PCR methods. Among the twenty eggs analyzed, three (15%) tested positive for Salmonella, while the remaining seventeen (85%) were confirmed as negative. Genotyping through multiplex PCR revealed the presence of two S. Enteritidis and other serovar, with the use of three specific gene sets: a random sequence for Salmonella spp., sdfI gene for S. Enteritidis, and flagellin (fliC gene) for S. Typhimurium. Out of the 20 isolates obtained from chicken meat, five (25%) were identified as S. Typhimurium, and three (15%) were classified as S. Enteritidis. All isolates sourced from chicken meat exhibited resistance to Rifampicin and Amoxicillin, with 90% displaying sensitivity to cefotaxime, gemifloxacin, and Erythromycin. Importantly, S. Blegdam, identified via serological methods, displayed resistance to all tested antibiotics. For the three isolates obtained from eggs, 66.6% showed sensitivity to cefotaxime, erythromycin, cefuraxime, and cefaclor, while displaying complete resistance (100%) to Amoxicillin, rifampicin, clarithromycin, and cefadroxil. Notably, one serovar exhibited absolute resistance to all tested drugs. CONCLUSION: Stakeholders must implement strict control measures and rationalize antibiotic use in veterinary and human medicine due to the rise of antibiotic-resistant strains.


Subject(s)
Anti-Bacterial Agents , Chickens , Eggs , Food Microbiology , Multiplex Polymerase Chain Reaction , Salmonella enteritidis , Salmonella typhimurium , Salmonella enteritidis/genetics , Salmonella enteritidis/drug effects , Salmonella enteritidis/isolation & purification , Multiplex Polymerase Chain Reaction/methods , Animals , Egypt , Chickens/microbiology , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Salmonella typhimurium/isolation & purification , Anti-Bacterial Agents/pharmacology , Eggs/microbiology , Food Microbiology/methods , Microbial Sensitivity Tests/methods , Genotype , Drug Resistance, Bacterial/genetics , Meat/microbiology , Genotyping Techniques/methods
7.
Nat Commun ; 15(1): 6123, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033143

ABSTRACT

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.


Subject(s)
Anti-Bacterial Agents , Biofilms , Drug Resistance, Multiple, Bacterial , Genome, Bacterial , Phylogeny , Salmonella typhimurium , Whole Genome Sequencing , Salmonella typhimurium/genetics , Salmonella typhimurium/drug effects , Salmonella typhimurium/isolation & purification , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Biofilms/drug effects , China , Genome, Bacterial/genetics , Plasmids/genetics , Microbial Sensitivity Tests , Humans , Salmonella Infections/microbiology
8.
Int J Radiat Biol ; 100(8): 1213-1225, 2024.
Article in English | MEDLINE | ID: mdl-39038272

ABSTRACT

PURPOSE: Nuclear applications are being increasingly used in various fields, necessitating studies to protect from radiation hazards and their effects. In this study, five different chemical structures of pyrazolo [3,4-b] pyridine derivatives were synthesized. The gamma and neutron radiation protective abilities of these samples were determined and demonstrated their potential use as ingredients in radioprotective drugs. MATERIAL AND METHODS: Gamma radiation absorption parameters were calculated both theoretical and experimental. Important attenuation parameters for fast neutrons (4.5 MeV energy radiation) were figured out using the Monte Carlo simulation Geant4 code. Additionally, experimental dose rates were measured for each sample and compared to those of Paraffin and high-density polyethylene, an organic substance. Besides, Ames/Salmonella test system was aimed to detecting genotoxicity features of pyrazolo pyridine derivatives. RESULTS: All results demonstrated that each sample possesses both gamma and neutron radiation attenuation capabilities. It was determined that sample PPC4 (C20H14BrN5) exhibited the highest gamma radiation attenuation capacity among all samples, while sample PPC2 (C22H20N6) displayed an excellent neutron stopping capacity. The genotoxic properties of pyrazolo[3,4-b] pyridine derivatives were examined using the Ames/Salmonella test, and as a result, it was determined that these substances did not exhibit genotoxic effects at test doses up to 5 mM. CONCLUSION: All obtained results indicate that all PPC (pyrazolo[3,4-b] pyridine derivatives) samples do not possess a toxic effect, and they can be utilized as an active substance for the development of a drug or cream with protective properties against both gamma and neutron radiations.


Subject(s)
Gamma Rays , Neutrons , Pyrazoles , Pyridines , Radiation-Protective Agents , Pyridines/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemistry , Pyrazoles/toxicity , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/chemistry , Mutagenicity Tests , Salmonella typhimurium/drug effects , Salmonella typhimurium/radiation effects , Dose-Response Relationship, Radiation , Monte Carlo Method
9.
Int J Mol Sci ; 25(14)2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39062920

ABSTRACT

Sensitive detection and efficient inactivation of pathogenic bacteria are crucial for halting the spread and reproduction of foodborne pathogenic bacteria. Herein, a novel Apt-modified PDMS-ZnO/Ag multifunctional biosensor has been developed for high-sensitivity surface-enhanced Raman scattering (SERS) detection along with photocatalytic sterilization towards Salmonella typhimurium (S. typhimurium). The distribution of the electric field in PDMS-ZnO/Ag with different Ag sputtering times was analyzed using a finite-difference time-domain (FDTD) algorithm. Due to the combined effect of electromagnetic enhancement and chemical enhancement, PDMS-ZnO/Ag exhibited outstanding SERS sensitivity. The limit of detection (LOD) for 4-MBA on the optimal SERS substrate (PZA-40) could be as little as 10-9 M. After PZA-40 was modified with the aptamer, the LOD of the PZA-40-Apt biosensor for detecting S. typhimurium was only 10 cfu/mL. Additionally, the PZA-40-Apt biosensor could effectively inactivate S. typhimurium under visible light irradiation within 10 min, with a bacterial lethality rate (Lb) of up to 97%. In particular, the PZA-40-Apt biosensor could identify S. typhimurium in food samples in addition to having minimal cytotoxicity and powerful biocompatibility. This work provides a multifunctional nanoplatform with broad prospects for selective SERS detection and photocatalytic sterilization of pathogenic bacteria.


Subject(s)
Biosensing Techniques , Salmonella typhimurium , Silver , Spectrum Analysis, Raman , Zinc Oxide , Biosensing Techniques/methods , Spectrum Analysis, Raman/methods , Silver/chemistry , Salmonella typhimurium/drug effects , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Catalysis , Metal Nanoparticles/chemistry , Hydrophobic and Hydrophilic Interactions , Dimethylpolysiloxanes/chemistry , Sterilization/methods , Limit of Detection
10.
Sci Rep ; 14(1): 17225, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060313

ABSTRACT

The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host-pathogen interface and identified several kinase inhibitors as potential HDTs.


Subject(s)
Macrophages , Mycobacterium tuberculosis , Protein Kinase Inhibitors , Salmonella typhimurium , Zebrafish , Animals , Humans , Salmonella typhimurium/drug effects , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/enzymology , Protein Kinase Inhibitors/pharmacology , Macrophages/microbiology , Macrophages/drug effects , Macrophages/metabolism , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Anti-Bacterial Agents/pharmacology , Cell Line , Embryo, Nonmammalian/drug effects , Tuberculosis/drug therapy , Tuberculosis/microbiology
11.
Nutrients ; 16(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38931255

ABSTRACT

Gut microbiota are the microbial organisms that play a pivotal role in intestinal health and during disease conditions. Keeping in view the characteristic functions of gut microbiota, in this study, Lactobacillus reuteri TPC32 (L. reuteri TPC32) was isolated and identified, and its whole genome was analyzed by the Illumina MiSeq sequencing platform. The results revealed that L. reuteri TPC32 had high resistance against acid and bile salts with fine in vitro antibacterial ability. Accordingly, a genome sequence of L. reuteri TPC32 has a total length of 2,214,495 base pairs with a guanine-cytosine content of 38.81%. Based on metabolic annotation, out of 2,212 protein-encoding genes, 118 and 101 were annotated to carbohydrate metabolism and metabolism of cofactors and vitamins, respectively. Similarly, drug-resistance and virulence genes were annotated using the comprehensive antibiotic research database (CARD) and the virulence factor database (VFDB), in which vatE and tetW drug-resistance genes were annotated in L. reuteri TPC32, while virulence genes are not annotated. The early prevention of L. reuteri TPC32 reduced the Salmonella typhimurium (S. Typhimurium) infection in mice. The results show that L. reuteri TPC32 could improve the serum IgM, decrease the intestinal cytokine secretion to relieve intestinal cytokine storm, reinforce the intestinal biochemical barrier function by elevating the sIgA expression, and strengthen the intestinal physical barrier function. Simultaneously, based on the 16S rRNA analysis, the L. reuteri TPC32 results affect the recovery of intestinal microbiota from disease conditions and promote the multiplication of beneficial bacteria. These results provide new insights into the biological functions and therapeutic potential of L. reuteri TPC32 for treating intestinal inflammation.


Subject(s)
Gastrointestinal Microbiome , Genome, Bacterial , Limosilactobacillus reuteri , Probiotics , Whole Genome Sequencing , Animals , Mice , Swine , Salmonella typhimurium/genetics , Salmonella typhimurium/drug effects , Anti-Bacterial Agents/pharmacology , Virulence Factors/genetics
12.
J Agric Food Chem ; 72(25): 14433-14447, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38866717

ABSTRACT

JHBp2 is a peptide purified from Jinhua ham broth with antibacterial activity against Salmonella typhimurium. Untargeted metabolomics and label-free quantitative proteomics were used to analyze metabolic and protein expression changes in S. typhimurium after JHBp2 treatment. Cell wall and membrane damage results indicate that JHBp2 has membrane-disruptive properties, causing leakage of intracellular nucleic acids and proteins. Metabolomics revealed 516 differentially expressed metabolites, involving cofactor biosynthesis, purine metabolism, ABC transporters, glutathione metabolism, pyrimidine metabolism, etc. Proteomics detected 735 differentially expressed proteins, involving pyruvate metabolism, amino acid biosynthesis, purine metabolism, carbon metabolism, glycolysis/gluconeogenesis, etc. RT-qPCR and proteomics results showed a positive correlation, and molecular docking demonstrated stable binding of JHBp2 to some differentially expressed proteins. In summary, JHBp2 could disrupt the S. typhimurium cell wall and membrane structure, interfere with synthesis of membrane-related proteins, trigger intracellular substance leak, and reduce levels of enzymes and metabolites involved in energy metabolism, amino acid anabolism, and nucleotide anabolism.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Metabolomics , Molecular Docking Simulation , Proteomics , Salmonella typhimurium , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Swine , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Peptides/chemistry , Peptides/pharmacology , Peptides/metabolism , Meat Products/microbiology , Meat Products/analysis
13.
Microbiol Res ; 285: 127773, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38833830

ABSTRACT

Salmonella is an important foodborne pathogen. Given the ban on the use of antibiotics during the egg-laying period in China, finding safe and effective alternatives to antibiotics to reduce Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infections in chickens is essential for the prevention and control of this pathogen and the protection of human health. Numerous studies have shown that unsaturated fatty acids have a positive effect on intestinal inflammation and resistance to infection by intestinal pathogens. Here we investigated the protective effect of α-linolenic acid (ALA) against S. Typhimurium infection in chickens and further explored its mechanism of action. We added different proportions of ALA to the feed and observed the effect of ALA on S. Typhimurium colonization using metagenomic sequencing technology and physiological index measurements. The role of gut flora on S. Typhimurium colonization was subsequently verified by fecal microbiota transplantation (FMT). We found that ALA protects chickens from S. Typhimurium infection by reducing intestinal inflammation through remodeling the gut microbiota, up-regulating the expression of ileocecal barrier-related genes, and maintaining the integrity of the intestinal epithelium. Our data suggest that supplementation of feed with ALA may be an effective strategy to alleviate S. Typhimurium infection in chickens.


Subject(s)
Cecum , Chickens , Dietary Supplements , Gastrointestinal Microbiome , Intestinal Mucosa , Poultry Diseases , Salmonella Infections, Animal , Salmonella typhimurium , alpha-Linolenic Acid , Animals , Chickens/microbiology , Salmonella typhimurium/drug effects , Gastrointestinal Microbiome/drug effects , alpha-Linolenic Acid/pharmacology , alpha-Linolenic Acid/administration & dosage , Salmonella Infections, Animal/prevention & control , Salmonella Infections, Animal/microbiology , Poultry Diseases/microbiology , Poultry Diseases/prevention & control , Intestinal Mucosa/microbiology , Cecum/microbiology , Animal Feed , Fecal Microbiota Transplantation
14.
Nat Commun ; 15(1): 5074, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871710

ABSTRACT

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Current susceptibility testing approaches limit our ability to rapidly distinguish between antimicrobial-susceptible and -resistant organisms. Salmonella Typhimurium (S. Typhimurium) is an enteric pathogen responsible for severe gastrointestinal illness and invasive disease. Despite widespread resistance, ciprofloxacin remains a common treatment for Salmonella infections, particularly in lower-resource settings, where the drug is given empirically. Here, we exploit high-content imaging to generate deep phenotyping of S. Typhimurium isolates longitudinally exposed to increasing concentrations of ciprofloxacin. We apply machine learning algorithms to the imaging data and demonstrate that individual isolates display distinct growth and morphological characteristics that cluster by time point and susceptibility to ciprofloxacin, which occur independently of ciprofloxacin exposure. Using a further set of S. Typhimurium clinical isolates, we find that machine learning classifiers can accurately predict ciprofloxacin susceptibility without exposure to it or any prior knowledge of resistance phenotype. These results demonstrate the principle of using high-content imaging with machine learning algorithms to predict drug susceptibility of clinical bacterial isolates. This technique may be an important tool in understanding the morphological impact of antimicrobials on the bacterial cell to identify drugs with new modes of action.


Subject(s)
Anti-Bacterial Agents , Ciprofloxacin , Drug Resistance, Bacterial , Machine Learning , Microbial Sensitivity Tests , Salmonella typhimurium , Ciprofloxacin/pharmacology , Salmonella typhimurium/drug effects , Salmonella typhimurium/isolation & purification , Anti-Bacterial Agents/pharmacology , Humans , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , Algorithms
15.
Food Microbiol ; 122: 104552, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38839232

ABSTRACT

In this study, we investigated the combined effect of 222 nm krypton-chlorine excilamp (EX) and 307 nm ultraviolet-B (UVB) light on the inactivation of Salmonella Typhimurium and Listeria monocytogenes on sliced cheese. The data confirmed that simultaneous exposure to EX and UVB irradiation for 80 s reduced S. Typhimurium and L. monocytogenes population by 3.50 and 3.20 log CFU/g, respectively, on sliced cheese. The synergistic cell count reductions in S. Typhimurium and L. monocytogenes in the combined treatment group were 0.88 and 0.59 log units, respectively. The inactivation mechanism underlying the EX and UVB combination treatment was evaluated using fluorescent staining. The combination of EX and UVB light induced the inactivation of reactive oxygen species (ROS) defense enzymes (superoxide dismutase) and synergistic ROS generation, resulting in synergistic lipid peroxidation and destruction of the cell membrane. There were no significant (P > 0.05) differences in the color, texture, or sensory attributes of sliced cheese between the combination treatment and control groups. These results demonstrate that combined treatment with EX and UVB light is a potential alternative strategy for inactivating foodborne pathogens in dairy products without affecting their quality.


Subject(s)
Cheese , Chlorine , Listeria monocytogenes , Reactive Oxygen Species , Salmonella typhimurium , Ultraviolet Rays , Cheese/microbiology , Cheese/analysis , Listeria monocytogenes/radiation effects , Listeria monocytogenes/growth & development , Listeria monocytogenes/drug effects , Salmonella typhimurium/radiation effects , Salmonella typhimurium/growth & development , Salmonella typhimurium/drug effects , Reactive Oxygen Species/metabolism , Chlorine/pharmacology , Food Irradiation/methods , Food Microbiology , Microbial Viability/radiation effects , Colony Count, Microbial
16.
PLoS Negl Trop Dis ; 18(6): e0012249, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38848444

ABSTRACT

INTRODUCTION: Salmonella is one of the most common causes of food-borne outbreaks and infection worldwide. Non-typhoidal Salmonella (NTS) infections are common and remain a significant public health problem among important bacterial foodborne diseases. The current study aimed to establish the Non typhoidal Salmonella infection and antimicrobial resistance status among selected patients at Morogoro Regional Referral Hospital (MRRH), Morogoro Region, Tanzania, to inform clinical care management and public health interventions. METHODOLOGY: A cross-sectional study was conducted using medical records and samples were collected from hospitalised and outpatients between October and December 2021. A total of 153 participants were enrolled in the study and 132 consented to being sampled. The collected samples were analysed using standard microbiological techniques. The isolates were subjected to molecular genotyping, where Polymerase Chain Reaction (PCR) was performed targeting the 16S rDNA gene. PCR products were then submitted for sequencing to establish phylogenetic relatedness. Antimicrobial susceptibility testing and resistance genes screening were also conducted. RESULTS: The phylogenetic analysis identified two Salmonella serovars; Salmonella Enteritidis and Salmonella Typhimurium. The isolates were from four adults and seven children patients. The isolates were tested against six antimicrobial agents: tetracycline, trimethoprim, gentamycin, ciprofloxacin, ampicillin and cefotaxime. Further antimicrobial assays were performed by screening 10 antimicrobial resistance genes using PCR. Overall, the highest resistance was observed in ampicillin (100%), whereas the lowest resistance was recorded for ciprofloxacin and gentamicin (9.1%). In addition, four (36.4%) of the isolates were resistant to cefotaxime and three (27.3%) to tetracycline and trimethoprim. The isolates also exhibit the presence of resistance genes for sulfamethoxazole 1&2, tetracycline (tet) A&B, Beta-lactamase CTXM, Beta-lactamase TEM, Beta-lactamase SHV, Gentamycine, Acra and acc3-1 in different occurrences. The overall prevalence of Salmonella species in Morogoro region was 8.3% (11/132) with Salmonella Enteritidis and Salmonella Typhimurium being the only serovars detected from adults and children stool samples. CONCLUSION: Our investigation showed that both children and adults had been exposed to Salmonella spp. However, the occurrence of NTS was higher in children (5.3% (7/132) compared to adults (3.0% (4/132). To stop zoonotic infections and the development of antimicrobial resistance in the community, this calls for Infection Prevention and Control (IPC) and stewardship programmes on rational use of antimicrobials in both health facilities and at the community level.


Subject(s)
Anti-Bacterial Agents , Salmonella Infections , Humans , Tanzania/epidemiology , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Adult , Child , Female , Male , Cross-Sectional Studies , Child, Preschool , Anti-Bacterial Agents/pharmacology , Adolescent , Young Adult , Middle Aged , Microbial Sensitivity Tests , Infant , Phylogeny , Salmonella/genetics , Salmonella/drug effects , Salmonella/classification , Salmonella/isolation & purification , Salmonella enteritidis/genetics , Salmonella enteritidis/drug effects , Salmonella enteritidis/isolation & purification , Salmonella enteritidis/classification , Gastrointestinal Diseases/microbiology , Gastrointestinal Diseases/epidemiology , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Salmonella typhimurium/isolation & purification , Aged , Drug Resistance, Bacterial
17.
Sci Rep ; 14(1): 14045, 2024 06 18.
Article in English | MEDLINE | ID: mdl-38890495

ABSTRACT

A composite of Zinc oxide loaded with 5-weight % silver decorated on carbon nanotubes (Ag-loaded ZnO: CNT) was synthesized using a simple refluxed chemical method. The influence of deviation in the weight % of carbon nanotube loading on photocatalytic dye degradation (methylene blue and rose bengal) and antibiotic (antimicrobial and antifungal) performance was investigated in this study. The light capture ability of Ag-loaded ZnO:CNT in the visible region was higher in photocatalytic activity than that of Ag-loaded ZnO and ZnO:CNT. The bandgap of the Ag-loaded ZnO: CNT was tuned owing to the surface plasmon resonance effect. The photocatalytic degradation investigations were optimized by varying the wt% in CNTs, pH of dye solution, concentration of the dye solution, and amount of catalytic dose. Around 100% photocatalytic efficiency in 2 min against MB dye was observed for Ag doped ZnO with 10 wt% CNT composite at pH 9, at a rate constant 1.48 min-1. Bipolaris sorokiniana fungus was first time tested against a composite material, which demonstrated optimum fungal inhibition efficiency of 48%. They were also tested against the bacterial strains Staphylococcus aureus, Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium, which showed promising antibacterial activity compared to commercially available drugs. The composite of Ag doped ZnO with 5 wt% CNT has shown competitive zone inhibition efficacy of 21.66 ± 0.57, 15.66 ± 0.57, 13.66 ± 0.57 against bacterial strains Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium which were tested for the first time against Ag-loaded ZnO:CNT.


Subject(s)
Anti-Bacterial Agents , Antifungal Agents , Nanotubes, Carbon , Silver , Zinc Oxide , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Silver/chemistry , Silver/pharmacology , Nanotubes, Carbon/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Catalysis , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Staphylococcus aureus/drug effects , Methylene Blue/chemistry , Methylene Blue/pharmacology , Coloring Agents/chemistry , Coloring Agents/pharmacology , Rose Bengal/chemistry , Rose Bengal/pharmacology , Microbial Sensitivity Tests , Salmonella typhimurium/drug effects , Hydrogen-Ion Concentration , Photolysis , Photochemical Processes
18.
Arch Microbiol ; 206(7): 302, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874634

ABSTRACT

Host-generated antimicrobial peptides (AMPs) play a pivotal role in defense against bacterial pathogens. AMPs kill invading bacteria majorly by disrupting the bacterial cell walls. AMPs are actively synthesized and released into the lumen of the gastrointestinal tract to limit colonization of enteric pathogens like Salmonella typhimurium (S. typhimurium). However, S. typhimurium has evolved several resistance mechanisms to defend AMPs. The multicomponent SapABCDF uptake transporter is one such system that helps in resisting AMPs. In the current study, we analyzed the role of S. typhimurium SapA against stress survival and virulence of this bacterium. ∆sapA mutant strain showed hypersensitivity to AMPs, like melittin and mastoparan. Further, ∆sapA mutant showed more than 22 folds (p = 0.019) hypersensitivity to neutrophils as compared to the WT strain of S. typhimurium. In addition, ∆sapA strain showed defective survival in mice. In conclusion, the results of the current study suggest that the SapA is essential for survival against AMPs and virulence of S. typhimurium.


Subject(s)
Neutrophils , Salmonella typhimurium , Animals , Salmonella typhimurium/drug effects , Salmonella typhimurium/pathogenicity , Salmonella typhimurium/genetics , Mice , Neutrophils/immunology , Neutrophils/microbiology , Virulence , Antimicrobial Peptides/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Female , Mice, Inbred BALB C , Salmonella Infections/microbiology , Antimicrobial Cationic Peptides/pharmacology
19.
Food Chem ; 456: 139948, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38852444

ABSTRACT

The natural vanilla market, which generates millions annually, is predominantly dependent on Vanilla planifolia, a species characterized by low genetic variability and susceptibility to pathogens. There is an increasing demand for natural vanilla, prized for its complex, authentic, and superior quality compared to artificial counterparts. Therefore, there is a necessity for innovative production alternatives to ensure a consistent and stable supply of vanilla flavors. In this context, vanilla crop wild relatives (WRs) emerge as promising natural sources of the spice. However, these novel species must undergo toxicity assessments to evaluate potential risks and ensure safety for consumption. This study aimed to assess the non-mutagenic and non-carcinogenic properties of ethanolic extracts from V. bahiana, V. chamissonis, V. cribbiana, and V. planifolia through integrated metabolomic profiling, in vitro toxicity assays, and in silico analyses. The integrated approach of metabolomics, in vitro assays, and in silico analyses has highlighted the need for further safety assessments of Vanilla cribbiana ethanolic extract. While the extracts of V. bahiana, V. chamissonis, and V. planifolia generally demonstrated non-mutagenic properties in the Ames assay, V. cribbiana exhibited mutagenicity at high concentrations (5000 µg/plate) in the TA98 strain without metabolic activation. This finding, coupled with the dose-dependent cytotoxicity observed in WST-1 (Water Soluble Tetrazolium) assays, a colorimetric method that assesses the viability of cells exposed to a test substance, underscores the importance of concentration in the safety evaluation of these extracts. Kaempferol and pyrogallol, identified with higher intensity in V. cribbiana, are potential candidates for in vitro mutagenicity. Although the results are not conclusive, they suggest the safety of these extracts at low concentrations. This study emphasizes the value of an integrated approach in providing a nuanced understanding of the safety profiles of natural products, advocating for cautious use and further research into V. cribbiana mutagenicity.


Subject(s)
Metabolomics , Plant Extracts , Vanilla , Plant Extracts/chemistry , Plant Extracts/toxicity , Brazil , Vanilla/chemistry , Humans , Forests , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Mutagenicity Tests , Computer Simulation
20.
Nat Microbiol ; 9(7): 1792-1811, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38862602

ABSTRACT

The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. oxytoca species complex strains can produce enterotoxins, namely, tilimycin and tilivalline, while also contributing to colonization resistance (CR). The relationship between these seemingly contradictory roles is not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis and various mouse models, we show that K. oxytoca provides CR against Salmonella Typhimurium. In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against Salmonella depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. This was linked to the relative levels of toxin-inducing carbohydrates in vivo. Finally, dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice. Together, this demonstrates that nutrient availability is key to both toxin-dependent and substrate-driven competition between K. oxytoca and Salmonella.


Subject(s)
Klebsiella oxytoca , Salmonella Infections , Salmonella typhimurium , Klebsiella oxytoca/genetics , Klebsiella oxytoca/metabolism , Animals , Mice , Salmonella Infections/microbiology , Salmonella typhimurium/genetics , Salmonella typhimurium/metabolism , Salmonella typhimurium/growth & development , Salmonella typhimurium/drug effects , Humans , Disease Models, Animal , Enterotoxins/metabolism , Enterotoxins/genetics , Female , Mice, Inbred C57BL , Klebsiella Infections/microbiology , Microbiota , Gastrointestinal Microbiome , Antibiosis , Benzodiazepinones
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