Transcriptional response in the peripheral blood of patients infected with Salmonella enterica serovar Typhi.
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ABSTRACT:
SUBMITTER: Thompson LJ
PROVIDER: S-EPMC2792164 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.
| S-EPMC5549772 | biostudies-other
Project description:Studies pertaining to Salmonella enterica serovar Typhimurium infection by utilizing model systems failed to mimic the essential aspects of immunity induced by Salmonella enterica serovar Typhi, as the determinants of innate immunity are distinct. The present study investigated the physiological and innate immune responses of S. Typhi infected Caenorhabditis elegans and also explored the Ty21a mediated immune enhancement in C. elegans. Ty21a is a known live vaccine for typhoidal infection in human beings. Physiological responses of C. elegans infected with S. Typhi assessed by survival and behavioral assays revealed that S. Typhi caused host mortality by persistent infection. However, Ty21a exposure to C. elegans was not harmful. Ty21a pre-exposed C. elegans, exhibited significant resistance against S. Typhi infection. Elevated accumulation of S. Typhi inside the infected host was observed when compared to Ty21a exposures. Transcript analysis of candidate innate immune gene (clec-60, clec-87, lys-7, ilys-3, scl-2, cpr-2, F08G5.6, atf-7, age-1, bec-1 and daf-16) regulations in the host during S. Typhi infection have been assessed through qPCR analysis to understand the activation of immune signaling pathways during S. Typhi infections. Gene silencing approaches confirmed that clec-60 and clec-87 has a major role in the defense system of C. elegans during S. Typhi infection. In conclusion, the study revealed that preconditioning of host with Ty21a protects against subsequent S. Typhi infection.
| S-EPMC3889844 | biostudies-other
Project description:Six sequencing libraries was prepared from S. Typhi planktonic cells and biofilm cells using Illumina HiSeq 2500 sequencing to investigate differential gene expression between the two conditions. The transcriptome was processed using Cufflinks and there were a total of 35 up-regulated genes and 29 down-regulated genes log2-fold change values of greater than 2 and less than negative 2. The differentially expressed genes were identified using BLAST and the functions was analysed. This study provides an overview of the genes that are differentially expressed in S. Typhi when it transitions from the planktonic to the biofilm phenotype. The data will provide a basis for further study is necessary to uncover the mechanisms of biofilm formation in S. Typhi and discovery of novel gene functions or pathways associated with the development of the typhoid carrier state. This data may also be used to elucidate the effect of biofilm on the virulence and pathogenicity of S. Typhi in chronic carriers.
2017-10-31 | GSE93686 | GEO
Project description:BackgroundTyphoid fever is an acute systemic infection of humans caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi). In chronic carriers, the bacteria survive the harsh environment of the gallbladder by producing biofilm. The phenotype of S. Typhi biofilm cells is significantly different from the free-swimming planktonic cells, and studies have shown that they are associated with antibiotic resistance, immune system evasion, and bacterial persistence. However, the mechanism of this transition and the events leading to biofilm formation are unknown. High throughput sequencing was performed to identify the genes involved in biofilm formation and to postulate the mechanism of action.ResultsPlanktonic S. Typhi cells were cultured using standard nutrient broth whereas biofilm cells were cultured in a stressful environment using high shearing-force and bile to mimic the gallbladder. Sequencing libraries were prepared from S. Typhi planktonic cells and mature biofilm cells using the Illumina HiSeq 2500 platform, and the transcriptome data obtained were processed using Cufflinks bioinformatics suite of programs to investigate differential gene expression between the two phenotypes. A total of 35 up-regulated and 29 down-regulated genes were identified. The identities of the differentially expressed genes were confirmed using NCBI BLAST and their functions were analyzed. The results showed that the genes associated with metabolic processes and biofilm regulations were down-regulated while those associated with the membrane matrix and antibiotic resistance were highly up-regulated.ConclusionsIt is proposed that the biofilm phenotype of S. Typhi allows the bacteria to increase production of the membrane matrix in order to serve as a physical shield and to adhere to surfaces, and enter an energy conservation state in response to the stressful environment. Conversely, the planktonic phenotype allows the bacteria to produce flagella and increase metabolic activity to enable the bacteria to migrate and form new colonies of infection. This data provide a basis for further studies to uncover the mechanism of biofilm formation in S. Typhi and to discover novel genes or pathways associated with the development of the typhoid carrier state.
| S-EPMC5664820 | biostudies-literature
Project description:pR(ST98) is a chimeric plasmid isolated from Salmonella enterica serovar Typhi (S. typhi) that mediates the functions of drug resistance and virulence. Previously, we reported that Salmonella plasmid virulence (spv) genes were present in S. typhi. In our current study, we investigated whether plasmid pR(ST98) exhibits significant cytotoxicity in macrophages. pR(ST98) was transferred into the avirulent Salmonella enterica serovar Typhimurium (S. typhimurium) strain RIA to create the transconjugant pR(ST98)/RIA. The standard S. typhimurium virulent strain SR-11, which carries a 100-kb virulence plasmid, was used as a positive control. The bacterial strains were incubated with a murine macrophage-like cell line (J774A.1) in vitro. Apoptosis of J774A.1 cells was examined by electron microscopy and flow cytometry after annexin-V/propidium iodide labeling, and the survival of Salmonella strains in J774A.1 cells was determined. Results showed that macrophages infected with strain pR(ST98)/RIA displayed greater levels of apoptosis than those infected with RIA and that pR(ST98 )may increase bacterial survival in macrophages. Further studies showed that the pR(ST98)-induced death of macrophages was associated with the loss of mitochondrial membrane potential and that pR(ST98 )may activate caspase-9 and then caspase-3. The research data indicate that the virulence of bacteria that contain the pR(ST98) plasmid is enhanced; the presence of this plasmid increases the survival of the bacterial pathogen and acts through the mitochondrial pathway to mediate macrophage apoptosis.
| S-EPMC4003229 | biostudies-other
Project description:BackgroundSalmonella enterica serovar Typhi (S. Typhi) is strictly a human intracellular pathogen. It causes acute systemic (typhoid fever) and chronic infections that result in long-term asymptomatic human carriage. S. Typhi displays diverse disease manifestations in human infection and exhibits high clonality. The principal factors underlying the unique lifestyle of S. Typhi in its human host during acute and chronic infections remain largely unknown and are therefore the main objective of this study.Methodology/principal findingsTo obtain insight into the intracellular lifestyle of S. Typhi, a high-throughput phenotypic microarray was employed to characterise the catabolic capacity of 190 carbon sources in S. Typhi strains. The success of this study lies in the carefully selected library of S. Typhi strains, including strains from two geographically distinct areas of typhoid endemicity, an asymptomatic human carrier, clinical stools and blood samples and sewage-contaminated rivers. An extremely low carbon catabolic capacity (27% of 190 carbon substrates) was observed among the strains. The carbon catabolic profiles appeared to suggest that S. Typhi strains survived well on carbon subtrates that are found abundantly in the human body but not in others. The strains could not utilise plant-associated carbon substrates. In addition, ?-glycerolphosphate, glycerol, L-serine, pyruvate and lactate served as better carbon sources to monosaccharides in the S. Typhi strains tested.ConclusionThe carbon catabolic profiles suggest that S. Typhi could survive and persist well in the nutrient depleted metabolic niches in the human host but not in the environment outside of the host. These findings serve as caveats for future studies to understand how carbon catabolism relates to the pathogenesis and transmission of this pathogen.
| S-EPMC3360705 | biostudies-literature
Project description:A salmonella genomic island, designated SGI11, was found in 18 of 26 multidrug-resistant Salmonella enterica serovar Typhi isolates from Bangladesh. SGI11 was an IS1 composite transposon and carried 7 resistance genes that conferred resistance to 5 first-line antimicrobials. Eleven of the 18 SGI11-carrying S. Typhi isolates had developed resistance to high levels of ciprofloxacin.
| S-EPMC4291426 | biostudies-literature
Project description:A chloramphenicol-resistant strain of Salmonella enterica serovar Typhi was first noted in Korea in 1992, when a resistant isolate was detected in a returned traveler. Continued isolation of multidrug-resistant (MDR) strains thereafter in other settings prompted a retrospective analysis of laboratory records and phenotypic and genotypic analyses of 12 chloramphenicol-resistant isolates. Among these, one isolate was resistant only to chloramphenicol, and the other isolates were also resistant to ampicillin and co-trimoxazole. MDR was transferred by conjugation from 9 of the 11 isolates. PCR showed that all isolates had an incompatible group HI1 plasmid, and oriT was detected in 10 isolates, which included strains with an unsuccessful transfer of resistance. All of the ampicillin-resistant isolates had a beta-lactamase band of pI 5.4 and bla(TEM) alleles. A PCR amplicon from an isolate showed that the sequences were identical to those of bla(TEM-1), suggesting that all isolates had a TEM-1 beta-lactamase. All isolates had class 1 integrons: 10 isolates had integrons of ca. 1.2 kb with dhfr7 gene cassettes, and 1 isolate had an integron of ca. 2.3 kb with aacA4 and bla(OXA-1)-like gene cassettes. The pulsed-field gel electrophoresis patterns of 7 of 11 MDR isolates were identical and indistinguishable from those reported for isolates in India and Indonesia. In conclusion, some of the MDR strains in Korea are related to those in other Asian countries. Susceptibility testing became necessary for selection of antimicrobial agents for the optimal treatment of patients with the emergence of MDR Salmonella serovar Typhi in Korea.
| S-EPMC525459 | biostudies-literature
Project description:We identified in the genome of Salmonella enterica serovar Typhi the gene encoding deoxyribokinase, deoK. Two other genes, vicinal to deoK, were determined to encode the putative deoxyribose transporter (deoP) and a repressor protein (deoQ). This locus, located between the uhpA and ilvN genes, is absent in Escherichia coli. The deoK gene inserted on a plasmid provides a selectable marker in E. coli for growth on deoxyribose-containing medium. Deoxyribokinase is a 306-amino-acid protein which exhibits about 35% identity with ribokinase from serovar Typhi, S. enterica serovar Typhimurium, or E. coli. The catalytic properties of the recombinant deoxyribokinase overproduced in E. coli correspond to those previously described for the enzyme isolated from serovar Typhimurium. From a sequence comparison between serovar Typhi deoxyribokinase and E. coli ribokinase, whose crystal structure was recently solved, we deduced that a key residue differentiating ribose and deoxyribose is Met10, which in ribokinase is replaced by Asn14. Replacement by site-directed mutagenesis of Met10 with Asn decreased the V(max) of deoxyribokinase by a factor of 2.5 and increased the K(m) for deoxyribose by a factor of 70, compared to the parent enzyme.
| S-EPMC94358 | biostudies-literature
Project description:Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region.
| S-EPMC7083327 | biostudies-literature