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Communications Biology Jun 2024Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58...
Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58 lineage, a lineage that arose comparatively recently before becoming globally disseminated. To better understand when and how H58 emerged and became dominant, we performed detailed phylogenetic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi organism, indicates that ancestral H58 organisms were already multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently.
Topics: Salmonella typhi; Typhoid Fever; Phylogeny; Humans; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Haplotypes; Mutation; Genome, Bacterial
PubMed: 38942806
DOI: 10.1038/s42003-024-06451-8 -
Open Veterinary Journal May 2024infections are considered the most common foodborne pathogens responsible for zoonotic infections and food poisoning in humans and animal species such as birds....
BACKGROUND
infections are considered the most common foodborne pathogens responsible for zoonotic infections and food poisoning in humans and animal species such as birds. Antimicrobial resistance is considered a global anxiety because it causes human public health repercussions, as well as leads to an increase in animal morbidity and death.
AIM
The aims of this study are the isolation and identification of , as well as to investigate the antimicrobial susceptibility test (AST) and the molecular characteristics using polymerase chain reaction (PCR) and sequences for isolates from chicken products (eggs, livers, and minced meat) and human in the Wasit Governorate of Iraq.
METHODS
A total of 300 samples (150 chicken product samples including eggs, livers, and minced meat, and 150 human fecal samples) were collected from the Wasit governorate of Iraq from January to December 2022. The bacterial isolation was done according to recommendations of ISO 6579 standard and the Global Foodborne Infections Network laboratory protocol. Serotyping test and AST were done by using 19 antibiotic agents according to the recommendations of the Clinical and Laboratory Standards Institute, 2022 by using disc diffusion susceptibility test and Vitik 2 test. Finally, the suspected isolates were confirmed using the conventional PCR method and sequencing for a unique gene.
RESULTS
The results showed that the isolation percentage of in chicken products was 8.66% (12% eggs, 6% livers, and 8% minced meat), while in humans it was 4.6%. Also, showed 100% of in humans. While, in chicken eggs , and were 50%, 33.33%, and 16.66%, respectively. Also, showed 100% of in both livers and minced meat. The AST in human isolates showed resistance to Ampicillin, Cefotaxime, Ceftazidime, Cefepime, Amikacin, Gentamicin, Ciprofloxacin, Norfloxacin, and Ceftriaxone, while no resistance to Amoxicillin, Pipracillin, Ertapenem, Imipenem, Meropenem, Fosfomycin, Nitrofurantoin, Trimethoprim, Azithromycin, and Tetracycline. In chicken products, isolates were resistant with different percentages to Amikacin, Gentamicin, Tetracycline, Ciprofloxacin, Norfloxacin, Nitrofurantoin, Ampicillin, Cefotaxime, Ceftazidime, Cefepime, and Trimethoprim; while no resistance to Amoxicillin, Pipracillin, Ertapenem, Imipenem, Meropenem, Fosfomycin, Azithromycin, and Ceftriaxone. Sequencing by using gene was done for four PCR products.
CONCLUSION
This study showed the presence of genetic mutations for which led to variations in the molecular characteristics, and antimicrobial drug resistance of isolated from chicken products and humans.
Topics: Animals; Salmonella enterica; Humans; Chickens; Iraq; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Meat; Feces; Poultry Products; Salmonella Infections
PubMed: 38938436
DOI: 10.5455/OVJ.2024.v14.i5.5 -
Animal Bioscience Jun 2024Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the...
OBJECTIVE
Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.
METHODS
In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine CSO22 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine CSO22 (pVAX-asd) orally.
RESULTS
The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p < 0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and IGF-1 in the serum of goats (p < 0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology (GO) of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto Encyclopedia of Genes and Genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. DGKK, CYTB, DUSP1 and LRAT) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.
CONCLUSION
Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic-pituitary-liver axis.
PubMed: 38938026
DOI: 10.5713/ab.24.0121 -
Vaccines Jun 2024Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain...
Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain for the expression of heterologous antigens for mucosal immunization. As the efficacy of any bacterial live vector vaccine correlates with its ability to express and present sufficient antigen, the genes for antigen expression are traditionally located on plasmids with antibiotic resistance genes for stabilization. However, for use in humans, antibiotic selection of plasmids is not applicable, leading to segregational loss of the antigen-producing plasmid. Therefore, we developed an oral Ty21a-based vaccine platform technology, the JMU-SalVac-system (Julius-Maximilians-Universität Würzburg) in which the antigen delivery plasmids (pSalVac-plasmid-series) are stabilized by a Δ/-based balanced-lethal system (BLS). The system is made up of the chromosomal knockout of the essential tyrosyl-tRNA-synthetase gene () and the in trans complementation of on the pSalVac-plasmid. Further novel functional features of the pSalVac-plasmids are the presence of two different expression cassettes for the expression of protein antigens. In this study, we present the construction of vaccine strains with BLS plasmids for antigen expression. The expression of cytosolic and secreted mRFP and cholera toxin subunit B (CTB) proteins as model antigens is used to demonstrate the versatility of the approach. As proof of concept, we show the induction of previously described in vivo inducible promoters cloned into pSalVac-plasmids during infection of primary macrophages and demonstrate the expression of model vaccine antigens in these relevant human target cells. Therefore, antigen delivery strains developed with the JMU-SalVac technology are promising, safe and stable vaccine strains to be used against mucosal infections in humans.
PubMed: 38932416
DOI: 10.3390/vaccines12060687 -
PloS One 2024Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure....
Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure. The rise of multidrug-resistant strains of S. typhi exacerbates this challenge, severely compromising conventional treatment efficacy due to over activity of efflux pumps. In our study, a comprehensive exploration of two fundamental aspects to combat MDR in S. typhi is carried out; i.e. employing advanced bioinformatics analyses and AlphaFold AI, We successfully identified and characterised a putative homologue, ABC-TPA, reminiscent of the P-glycoprotein (P-gp) known for its role in multidrug resistance in diverse pathogens. This discovery provides a critical foundation for understanding the potential mechanisms driving antibiotic resistance in S. typhi. Furthermore, employing computational methodologies, We meticulously assessed the potential of lignans, specifically Schisandrin A, B, and C, as promising Efflux Pump Inhibitors (EPIs) against the identified P-gp homologue in S. typhi. Noteworthy findings revealed robust binding interactions of Schisandrin A and B with the target protein, indicating substantial inhibitory capabilities. In contrast, Schisandrin C exhibited instability, showing varied effectiveness among the evaluated lignans. Pharmacokinetics and toxicity predictions underscored the favourable attributes of Schisandrin A, including prolonged action duration. Furthermore, high systemic stability and demanished toxicity profile of SA and SB present their therapeutic efficacy against MDR. This comprehensive investigation not only elucidates potential therapeutic strategies against MDR strains of S. typhi but also highlights the relevance of computational approaches in identifying and evaluating promising candidates. These findings lay a robust foundation for future empirical studies to address the formidable challenges antibiotic resistance poses in this clinically significant infectious diseases.
Topics: Salmonella typhi; Drug Resistance, Multiple, Bacterial; Lignans; Anti-Bacterial Agents; Bacterial Proteins; Humans; Microbial Sensitivity Tests; Computational Biology
PubMed: 38917154
DOI: 10.1371/journal.pone.0303285 -
PLoS Neglected Tropical Diseases Jun 2024Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans...
BACKGROUND
Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce.
METHODS
We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models.
RESULTS
We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection.
CONCLUSION
In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.
PubMed: 38913735
DOI: 10.1371/journal.pntd.0012273 -
Dose-response : a Publication of... 2024This study focuses on the investigation of the significance of polymers in drug delivery approaches. The carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA) and...
This study focuses on the investigation of the significance of polymers in drug delivery approaches. The carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA) and dextrin-based hydrogel membrane were prepared and employed for the sustained release of third-generation oral antibiotic (cefixime). Different proportions of CMC, PVA and dextrin were blended and hydrogel membranes were fabricated via solvent casting method. The prepared membrane was characterized by FTIR, SEM, UV-visible, TGA and swelling analysis. Cefixime drug was incorporated in the CMC/PVA/dextrin matrix and drug release was investigated. The sustained release of the tested drug (cefixime) was investigated and the drug was released in 120 min in the phosphate-buffered saline (PBS) solution. The antibacterial activity of the prepared membrane was promising against , and strains. The swelling capabilities, thermal stability and non-toxic nature of the prepared CMC/PVA/dextrin membrane could have potential applications for cefixime drug in delivery in a controlled way for the treatment of infectious diseases.
PubMed: 38912332
DOI: 10.1177/15593258241264951 -
Nature Communications Jun 2024Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi...
Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control Vi polymerization or acetylation is enough to result in different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper Vi capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo Vi capsule variants have primarily been identified in Africa, whereas the hyper Vi capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.
Topics: Salmonella typhi; Animals; Mice; Virulence; Polysaccharides, Bacterial; Mutation, Missense; Bacterial Capsules; Typhoid Fever; Humans; Bacterial Proteins; Virulence Factors; Female; Whole Genome Sequencing
PubMed: 38898034
DOI: 10.1038/s41467-024-49590-6 -
PLoS Neglected Tropical Diseases Jun 2024Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has increased in prevalence in recent decades in certain endemic regions in comparison to S....
Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has increased in prevalence in recent decades in certain endemic regions in comparison to S. Typhi, the most prevalent cause of enteric fever. Despite this increase, data on the prevalence and molecular epidemiology of S. Paratyphi A remain generally scarce. Here, we analysed the whole genome sequences of 216 S. Paratyphi A isolates originating from Kathmandu, Nepal between 2005 and 2014, of which 200 were from patients with acute enteric fever and 16 from the gallbladder of people with suspected chronic carriage. By exploiting the recently developed genotyping framework for S. Paratyphi A (Paratype), we identified several genotypes circulating in Kathmandu. Notably, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and systematically replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced susceptibility to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes encoding the type 3 secretion systems. Finally, we show that person-to-person is likely the most common mode of transmission and chronic carriers seem to play a limited role in maintaining disease circulation.
Topics: Nepal; Humans; Salmonella paratyphi A; Genotype; Retrospective Studies; Paratyphoid Fever; Male; Adult; Female; Young Adult; Adolescent; Child; Prevalence; Middle Aged; Molecular Epidemiology; Child, Preschool; Whole Genome Sequencing; Anti-Bacterial Agents; Phylogeny
PubMed: 38889189
DOI: 10.1371/journal.pntd.0011864 -
Bioresources and Bioprocessing Jun 2024Nanoparticles (NPs) formulation in biopolymers is an attractive process for the researcher to decrease the disadvantages of NPs application alone. Bimetallic NPs are a...
Nanoparticles (NPs) formulation in biopolymers is an attractive process for the researcher to decrease the disadvantages of NPs application alone. Bimetallic NPs are a promising formula of two NPs that usually act as synergetic phenomena. Zinc oxide and gold NPs (ZnO@AuNPs) biosynthesis as a bimetallic was prepared via the eco-friendly manner currently. Carboxymethylcellulose (CMC) was employed for the formulation of ZnO@AuNPs as a nanocomposite via a green method. Physicochemical and topographical characterization was assigned to ZnO@AuNPs and nanocomposite features. The nanostructure of bimetallic NPs and nanocomposite were affirmed with sizes around 15 and 25 nm, respectively. Indeed, the DLS measurements affirmed the more reasonable size and stability of the prepared samples as 27 and 93 nm for bimetallic NPs and nanocomposite, respectively. The inhibitory potential of nanocomposite was more than ZnO@AuNPs against Staphylococcus aureus, Escherichia coli, Salmonella typhi, Enterococcus faecalis, Mucor albicans, Aspergillus flavus, and Mucor circinelloid. ZnO@AuNPs and nanocomposite exhibited antioxidant activity via DPPH with IC of 71.38 and 32.4 µg/mL, correspondingly. Excellent anti-diabetic potential of nanocomposite with IC of 7.4 µg/mL, and ZnO@AuNPs with IC of 9.7 µg/mL was reported compared with the standard acarbose with the IC of 50.93 µg/mL for amylase inhibition (%). Photocatalytic degradation of RR195 and RB dyes was performed by ZnO@AuNPs and nanocomposite, where maximum degradation was 85.7 ± 1.53 and 88.7 ± 0.58%, respectively using ZnO@AuNPs, 90.3 ± 0.28 and 91.8 ± 0.27%, respectively using nanocomposite at 100 min.
PubMed: 38884830
DOI: 10.1186/s40643-024-00759-3