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1.
Biomedica ; 44(2): 258-276, 2024 05 30.
Article in English, Spanish | MEDLINE | ID: mdl-39088536

ABSTRACT

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.


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.
PLoS Biol ; 22(8): e3002731, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39102375

ABSTRACT

Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection.


Subject(s)
Polyamines , Salmonella typhimurium , Type III Secretion Systems , Virulence Factors , Salmonella typhimurium/metabolism , Salmonella typhimurium/pathogenicity , Salmonella typhimurium/genetics , Animals , Polyamines/metabolism , Mice , Type III Secretion Systems/metabolism , Type III Secretion Systems/genetics , Virulence Factors/metabolism , Virulence Factors/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Host-Pathogen Interactions , Humans , Salmonella Infections/metabolism , Salmonella Infections/microbiology , Female
3.
PLoS Biol ; 22(8): e3002746, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39110680

ABSTRACT

Understanding the dynamic evolution of Salmonella is vital for effective bacterial infection management. This study explores the role of the flexible genome, organised in regions of genomic plasticity (RGP), in shaping the pathogenicity of Salmonella lineages. Through comprehensive genomic analysis of 12,244 Salmonella spp. genomes covering 2 species, 6 subspecies, and 46 serovars, we uncover distinct integration patterns of pathogenicity-related gene clusters into RGP, challenging traditional views of gene distribution. These RGP exhibit distinct preferences for specific genomic spots, and the presence or absence of such spots across Salmonella lineages profoundly shapes strain pathogenicity. RGP preferences are guided by conserved flanking genes surrounding integration spots, implicating their involvement in regulatory networks and functional synergies with integrated gene clusters. Additionally, we emphasise the multifaceted contributions of plasmids and prophages to the pathogenicity of diverse Salmonella lineages. Overall, this study provides a comprehensive blueprint of the pathogenicity potential of Salmonella. This unique insight identifies genomic spots in nonpathogenic lineages that hold the potential for harbouring pathogenicity genes, providing a foundation for predicting future adaptations and developing targeted strategies against emerging human pathogenic strains.


Subject(s)
Genome, Bacterial , Salmonella , Salmonella/genetics , Salmonella/pathogenicity , Genome, Bacterial/genetics , Virulence/genetics , Humans , Genomics/methods , Multigene Family , Phylogeny , Plasmids/genetics , Salmonella Infections/microbiology , Prophages/genetics , Evolution, Molecular
4.
Ann Clin Microbiol Antimicrob ; 23(1): 70, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39113073

ABSTRACT

BACKGROUND: The increased resistance rate of Salmonella to third-generation cephalosporins represented by ceftriaxone (CRO) may result in the failure of the empirical use of third-generation cephalosporins for the treatment of Salmonella infection in children. The present study was conducted to evaluate a novel method for the rapid detection of CRO-resistant Salmonella (CRS). METHODS: We introduced the concept of the ratio of optical density (ROD) with and without CRO and combined it with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a new protocol for the rapid detection of CRS. RESULTS: The optimal incubation time and CRO concentration determined by the model strain test were 2 h and 8 µg/ml, respectively. We then conducted confirmatory tests on 120 clinical strains. According to the receiver operating characteristic curve analysis, the ROD cutoff value for distinguishing CRS and non-CRS strains was 0.818 [area under the curve: 1.000; 95% confidence interval: 0.970-1.000; sensitivity: 100.00%; specificity: 100%; P < 10- 3]. CONCLUSIONS: In conclusion, the protocol for the combined ROD and MALDI-TOF MS represents a rapid, accurate, and economical method for the detection of CRS.


Subject(s)
Anti-Bacterial Agents , Ceftriaxone , Microbial Sensitivity Tests , Salmonella Infections , Salmonella , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Ceftriaxone/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Salmonella/drug effects , Salmonella Infections/microbiology , Microbial Sensitivity Tests/methods , Drug Resistance, Bacterial , Sensitivity and Specificity , ROC Curve
5.
Vaccine ; 42(19S1): S101-S124, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39003017

ABSTRACT

Invasive non-typhoidal Salmonella (iNTS) disease is an under-recognized high-burden disease causing major health and socioeconomic issues in sub-Saharan Africa (sSA), predominantly among immune-naïve infants and young children, including those with recognized comorbidities such as HIV infection. iNTS disease is primarily caused by Salmonella enterica serovar Typhimurium sequence type (ST) 313 and 'African-restricted clades' of Salmonella Enteritidis ST11 that have emerged across the African continent as a series of epidemics associated with acquisition of new antimicrobial resistance. Due to genotypes with a high prevalence of antimicrobial resistance and scarcity of therapeutic options, these NTS serovars are designated by the World Health Organization as a priority pathogen for research and development of interventions, including vaccines, to address and reduce NTS associated bacteremia and meningitis in sSA. Novel and traditional vaccine technologies are being applied to develop vaccines against iNTS disease, and the results of the first clinical trials in the infant target population should become available in the near future. The "Vaccine Value Profile" (VVP) addresses information related predominantly to invasive disease caused by Salmonella Enteritidis and Salmonella Typhimurium prevalent in sSA. Information is included on stand-alone iNTS disease candidate vaccines and candidate vaccines targeting iNTS disease combined with another invasive serotype, Salmonella Typhi, that is also common across sSA. Out of scope for the first version of this VVP is a wider discussion on either diarrheagenic NTS disease (dNTS) also associated with Salmonella Enteritidis and Salmonella Typhimurium or the development of a multivalent Salmonella vaccines targeting key serovars for use globally. This VVP for vaccines to prevent iNTS disease is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic, and societal value of pipeline vaccines and vaccine-like products. Future versions of this VVP will be updated to reflect ongoing activities such as vaccine development strategies and a "Full Vaccine Value Assessment" that will inform the value proposition of an iNTS disease vaccine. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the World Health Organization African Region. All contributors have extensive expertise on various elements of the iNTS disease VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.


Subject(s)
Salmonella Infections , Salmonella Vaccines , Salmonella enteritidis , Humans , Africa South of the Sahara/epidemiology , Salmonella enteritidis/immunology , Salmonella enteritidis/genetics , Salmonella enteritidis/pathogenicity , Salmonella Infections/prevention & control , Salmonella Infections/epidemiology , Salmonella Infections/microbiology , Salmonella Infections/immunology , Salmonella typhimurium/immunology , Salmonella typhimurium/pathogenicity , Salmonella typhimurium/genetics , Salmonella Vaccines/immunology , Salmonella Vaccines/administration & dosage
6.
Sci Rep ; 14(1): 15160, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956132

ABSTRACT

In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.


Subject(s)
Cell Differentiation , ErbB Receptors , Organoids , Salmonella Infections , Salmonella typhimurium , Stem Cells , Animals , Organoids/microbiology , Stem Cells/metabolism , Mice , Salmonella typhimurium/pathogenicity , Salmonella typhimurium/physiology , Salmonella Infections/microbiology , Salmonella Infections/pathology , ErbB Receptors/metabolism , ErbB Receptors/genetics , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Cell Proliferation , Disease Models, Animal , Mice, Inbred C57BL
7.
BMC Infect Dis ; 24(1): 669, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965458

ABSTRACT

BACKGROUND: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. CASE PRESENTATION: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. CONCLUSIONS: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.


Subject(s)
Sepsis , Humans , Male , Middle Aged , Sepsis/microbiology , Sepsis/complications , Aorta, Abdominal/surgery , Aorta, Abdominal/microbiology , Enterococcus faecium/isolation & purification , Anti-Bacterial Agents/therapeutic use , Streptococcus anginosus/isolation & purification , Intestinal Fistula/microbiology , Intestinal Fistula/surgery , Intestinal Fistula/complications , Salmonella/isolation & purification , Escherichia coli/isolation & purification , Recurrence , Duodenal Diseases/microbiology , Duodenal Diseases/surgery , Duodenal Diseases/complications , Salmonella Infections/microbiology , Salmonella Infections/complications , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy
9.
Virulence ; 15(1): 2384553, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39080852

ABSTRACT

Salmonella is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that Salmonella Typhimurium (STM) infection of the intestinal tract of mice led to a significant increase in the proportion of Lacticaseibacillus, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding Lacticaseibacillus rhamnosus GG (LGG) effectively alleviated the infection of STM in the mouse intestines. TLR2-/- mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for LGG's activation of ILC3. Subsequent in vitro experiments showed that heat-killed LGG (HK-LGG) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit STM infection. This study demonstrates that oral administration of LGG is a potential method for inhibiting STM infection.


Subject(s)
Interleukin-22 , Interleukins , Lacticaseibacillus rhamnosus , Lymphocytes , Salmonella Infections , Salmonella typhimurium , Toll-Like Receptor 2 , Animals , Mice , Salmonella typhimurium/immunology , Toll-Like Receptor 2/immunology , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Lymphocytes/immunology , Lacticaseibacillus rhamnosus/immunology , Salmonella Infections/immunology , Salmonella Infections/microbiology , Interleukins/immunology , Interleukins/metabolism , Mice, Knockout , Mice, Inbred C57BL , Dendritic Cells/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Immunity, Innate , Probiotics/administration & dosage , Immunity, Mucosal
10.
Open Vet J ; 14(6): 1313-1329, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39055762

ABSTRACT

Salmonellosis, caused by Salmonella species, is one of the most common foodborne illnesses worldwide with an estimated 93.8 million cases and about 155,00 fatalities. In both industrialized and developing nations, Salmonellosis has been reported to be one of the most prevalent foodborne zoonoses and is linked with arrays of illness syndromes such as acute and chronic enteritis, and septicaemia. The two major and most common Salmonella species implicated in both warm-blooded and cold-blooded animals are Salmonella bongori and Salmonella enterica. To date, more than 2400 S. enterica serovars which affect both humans and animals have been identified. Salmonella is further classified into serotypes based on three primary antigenic determinants: somatic (O), flagella (H), and capsular (K). The capacity of nearly all Salmonella species to infect, multiply, and survive in human host cells with the aid of their pathogenic and virulence arsenals makes them deadly and important public health pathogens. Primarily, food-producing animals such as poultry, swine, cattle, and their products have been identified as important sources of salmonellosis. Additionally, raw fruits and vegetables are among other food types that have been linked to the spread of Salmonella spp. Based on the clinical manifestation of human salmonellosis, Salmonella strains can be categorized as either non-typhoidal Salmonella (NTS) and typhoidal Salmonella. The detection of aseptically collected Salmonella in necropsies, environmental samples, feedstuffs, rectal swabs, and food products serves as the basis for diagnosis. In developing nations, typhoid fever due to Salmonella Typhi typically results in the death of 5%-30% of those affected. The World Health Organization (WHO) calculated that there are between 16 and 17 million typhoid cases worldwide each year, with scaring 600,000 deaths as a result. The contagiousness of a Salmonella outbreak depends on the bacterial strain, serovar, growth environment, and host susceptibility. Risk factors for Salmonella infection include a variety of foods; for example, contaminated chicken, beef, and pork. Globally, there is a growing incidence and emergence of life-threatening clinical cases, especially due to multidrug-resistant (MDR) Salmonella spp, including strains exhibiting resistance to important antimicrobials such as beta-lactams, fluoroquinolones, and third-generation cephalosporins. In extreme cases, especially in situations involving very difficult-to-treat strains, death usually results. The severity of the infections resulting from Salmonella pathogens is dependent on the serovar type, host susceptibility, the type of bacterial strains, and growth environment. This review therefore aims to detail the nomenclature, etiology, history, pathogenesis, reservoir, clinical manifestations, diagnosis, epidemiology, transmission, risk factors, antimicrobial resistance, public health importance, economic impact, treatment, and control of salmonellosis.


Subject(s)
Salmonella Infections , Animals , Humans , Risk Factors , Salmonella Infections/epidemiology , Salmonella Infections/microbiology , Salmonella Infections, Animal/microbiology , Salmonella Infections, Animal/epidemiology , Salmonella/classification , Salmonella/physiology , Salmonella/isolation & purification , Zoonoses
11.
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
12.
Sci Rep ; 14(1): 17225, 2024 07 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
13.
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
14.
ACS Infect Dis ; 10(8): 3052-3058, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39054961

ABSTRACT

Effective molecular strategies are needed to target pathogenic bacteria that thrive and proliferate within mammalian cells, a sanctuary inaccessible to many therapeutics. Herein, we present a class of cationic amphiphilic polyproline helices (CAPHs) with a rigid placement of the cationic moiety on the polyproline helix and assess the role of configuration of the unnatural proline residues making up the CAPHs. By shortening the distance between the guanidinium side chain and the proline backbone of the agents, a notable increase in cellular uptake and antibacterial activity was observed, whereas changing the configuration of the moieties on the pyrrolidine ring from cis to trans resulted in more modest increases. When the combination of these two activities was evaluated, the more rigid CAPHs were exceptionally effective at eradicating intracellular methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella infections within macrophages, significantly exceeding the clearance with the parent CAPH.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Peptides , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Peptides/chemistry , Peptides/pharmacology , Macrophages/drug effects , Microbial Sensitivity Tests , Cations/chemistry , Cations/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Humans , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology
15.
PLoS One ; 19(7): e0292413, 2024.
Article in English | MEDLINE | ID: mdl-38959229

ABSTRACT

Salmonella infections pose a significant global public health concern due to the substantial expenses associated with monitoring, preventing, and treating the infection. In this study, we explored the core proteome of Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins were curated from 30 different isolates of Salmonella (strain NZ CP014051 was taken as reference). Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related to biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multi-epitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine could be highly antigenic, non-toxic, non-allergic, and have suitable physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit a robust immune response. Using in vitro, in vivo, and clinical trials, our findings could yield a Pan-Salmonella vaccine that might provide protection against various Salmonella species.


Subject(s)
Computational Biology , Epitopes, T-Lymphocyte , Proteomics , Salmonella , Proteomics/methods , Epitopes, T-Lymphocyte/immunology , Salmonella/immunology , Salmonella/genetics , Computational Biology/methods , Humans , Genomics/methods , Molecular Docking Simulation , Salmonella Vaccines/immunology , Animals , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Molecular Dynamics Simulation , Salmonella Infections/prevention & control , Salmonella Infections/immunology , Salmonella Infections/microbiology , Epitopes, B-Lymphocyte/immunology , Immunoinformatics
16.
Georgian Med News ; (349): 98-102, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38963211

ABSTRACT

We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient's condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.


Subject(s)
Salmonella Infections , Adult , Female , Humans , Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Diarrhea/microbiology , Meropenem/therapeutic use , Multiple Organ Failure/microbiology , Multiple Organ Failure/etiology , Respiratory Distress Syndrome/microbiology , Respiratory Distress Syndrome/etiology , Salmonella Infections/diagnosis , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Salmonella Infections/complications , Salmonella typhimurium/isolation & purification
17.
Gut Microbes ; 16(1): 2369339, 2024.
Article in English | MEDLINE | ID: mdl-38962965

ABSTRACT

The bacterial species Salmonella enterica (S. enterica) is a highly diverse pathogen containing more than 2600 distinct serovars, which can infect a wide range of animal and human hosts. Recent global emergence of multidrug resistant strains, from serovars Infantis and Muenchen is associated with acquisition of the epidemic megaplasmid, pESI that augments antimicrobial resistance and pathogenicity. One of the main pESI's virulence factors is the potent iron uptake system, yersiniabactin encoded by fyuA, irp2-irp1-ybtUTE, ybtA, and ybtPQXS gene cluster. Here we show that yersiniabactin, has an underappreciated distribution among different S. enterica serovars and subspecies, integrated in their chromosome or carried by different conjugative plasmids, including pESI. While the genetic organization and the coding sequence of the yersiniabactin genes are generally conserved, a 201-bp insertion sequence upstream to ybtA, was identified in pESI. Despite this insertion, pESI-encoded yersiniabactin is regulated by YbtA and the ancestral Ferric Uptake Regulator (Fur), which binds directly to the ybtA and irp2 promoters. Furthermore, we show that yersiniabactin genes are specifically induced during the mid-late logarithmic growth phase and in response to iron-starvation or hydrogen peroxide. Concurring, yersiniabactin was found to play a previously unknown role in oxidative stress tolerance and to enhance intestinal colonization of S. Infantis in mice. These results indicate that yersiniabactin contributes to Salmonella fitness and pathogenicity in vivo and is likely to play a role in the rapid dissemination of pESI among globally emerging Salmonella lineages.


Subject(s)
Bacterial Proteins , Gene Expression Regulation, Bacterial , Iron , Oxidative Stress , Salmonella enterica , Animals , Iron/metabolism , Mice , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Salmonella enterica/genetics , Salmonella enterica/metabolism , Salmonella enterica/pathogenicity , Virulence/genetics , Phenols/metabolism , Thiazoles/metabolism , Humans , Salmonella Infections/microbiology , Gene Transfer, Horizontal , Female , Virulence Factors/genetics , Virulence Factors/metabolism , Plasmids/genetics
18.
Open Vet J ; 14(5): 1117-1129, 2024 May.
Article in English | MEDLINE | ID: mdl-38938436

ABSTRACT

Background: Salmonella 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 Salmonella enterica, 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 rRNA gene. Results: The results showed that the isolation percentage of S. enterica 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 Salmonella typhi in humans. While, in chicken eggs S. typhi, Salmonella typhimurium, and Salmonella enteritidis were 50%, 33.33%, and 16.66%, respectively. Also, showed 100% of S. typhimurium 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 rRNA gene was done for four PCR products. Conclusion: This study showed the presence of genetic mutations for S. enterica which led to variations in the molecular characteristics, and antimicrobial drug resistance of S. enterica isolated from chicken products and humans.


Subject(s)
Anti-Bacterial Agents , Chickens , Drug Resistance, Bacterial , Salmonella enterica , Animals , Salmonella enterica/drug effects , Salmonella enterica/isolation & purification , Salmonella enterica/genetics , Humans , Chickens/microbiology , Iraq/epidemiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests/veterinary , Meat/microbiology , Feces/microbiology , Poultry Products/microbiology , Salmonella Infections/microbiology , Salmonella Infections/epidemiology
19.
Methods Mol Biol ; 2813: 19-37, 2024.
Article in English | MEDLINE | ID: mdl-38888768

ABSTRACT

Genomics has revolutionized how we characterize and monitor infectious diseases for public health. The surveillance and characterization of Salmonella has improved drastically within the past decade. In this chapter, we discuss the prerequisites for good bacterial genomics studies and make note of advantages and disadvantages of this research approach. We discuss methods for outbreak detection and the evolutionary and epidemiological characterization of Salmonella spp. We provide an outline for determining the sequence type and serotype of isolates, building a core genome phylogenetic tree, and detecting antimicrobial resistance genes, virulence factors, and mobile genetic elements. These methods can be used to study other pathogenic bacterial species.


Subject(s)
Genome, Bacterial , Genomics , Molecular Epidemiology , Phylogeny , Salmonella Infections , Salmonella , Salmonella/genetics , Humans , Genomics/methods , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Molecular Epidemiology/methods , Virulence Factors/genetics , Disease Outbreaks , Drug Resistance, Bacterial/genetics , Interspersed Repetitive Sequences/genetics
20.
Methods Mol Biol ; 2813: 107-115, 2024.
Article in English | MEDLINE | ID: mdl-38888773

ABSTRACT

Mass spectrometry-based proteomics provides a wealth of information about changes in protein production and abundance under diverse conditions, as well as mechanisms of regulation, signaling cascades, interaction partners, and communication patterns across biological systems. For profiling of intracellular pathogens, proteomic profiling can be performed in the absence of a host to singularly define the pathogenic proteome or during an infection-like setting to identify dual perspectives of infection. In this chapter, we present techniques to extract proteins from the human bacterial intracellular pathogen, Salmonella enterica serovar Typhimurium, in the presence of macrophages, an important innate immune cell in host defense. We outline sample preparation, including protein extraction, digestion, and purification, as well as mass spectrometry measurements and bioinformatics analysis. The data generated from our dual perspective profiling approach provides new insight into pathogen and host protein modulation under infection-like conditions.


Subject(s)
Bacterial Proteins , Macrophages , Proteomics , Salmonella typhimurium , Salmonella typhimurium/metabolism , Salmonella typhimurium/pathogenicity , Proteomics/methods , Humans , Bacterial Proteins/metabolism , Macrophages/microbiology , Macrophages/metabolism , Host-Pathogen Interactions , Proteome/metabolism , Salmonella Infections/microbiology , Salmonella Infections/metabolism , Salmonella Infections/immunology , Computational Biology/methods , Mass Spectrometry/methods
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