Biology subjects

Patel, V.

Publications and source records attributed to Patel, V..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1g, 10-500Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in CHO-adherent cells (+79% in 96h) using a particular set of LIV parameters (0.2g, 500Hz, 3x30 min/d, 2h refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Exposing these same CHO-suspension cells to distinct LIV parameters (30Hz, 0.7g, 2x60 min/d, 2h refractory period) increased proliferation by 210%. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, its highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.

bioengineering↗

bioRxiv2023

Monomethylation of Lysine 27 at Histone 3 Confers Lifelong Susceptibility to Stress

Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling, and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice exposed to early life stress (ELS) or to chronic social defeat stress (CSDS) in adulthood displayed increased enrichment of H3K27me1, and transient decreases in H3K27me2, in the nucleus accumbens (NAc), a key brain-reward region. Stress induction of H3K27me1 was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which is induced by chronic stress and controls H3K27 methylation patterns. Overexpression of the VEFS domain led to social, emotional, and cognitive abnormalities, and altered excitability of NAc D1 mediums spiny neurons. Together, we describe a novel function of H3K27me1 in brain and demonstrate its role as a "chromatin scar" that mediates lifelong stress susceptibility.

neuroscience↗

bioRxiv2022

LHX2 in germ cells control tubular organization in the developing mouse testis

In the gonads of mammalian XY embryos, the organization of cords is the hallmark of testis development. This organization is thought to be controlled by interactions of the Sertoli cells, endothelial and interstitial cells with little or no role of germ cells. Challenging this notion, herein we show that the germ cells play an active role in the organization of the testicular tubules. We observed that the LIM-homeobox gene, Lhx2 is expressed in the germ cells of the developing testis between E12.5-E15.5. In Lhx2 knockout-fetal testis there was altered expression of several genes not just in germ cells but also in the supporting (Sertoli) cells, endothelial cells, and interstitial cells. Further, loss of Lhx2 led to disrupted endothelial cell migration and expansion of interstitial cells in the XY gonads. The cords in the developing testis of Lhx2 knockout embryos are disorganized with a disrupted basement membrane. Together, our results show an important role of Lhx2 in testicular development and imply the involvement of germ cells in the tubular organization of the differentiating testis. HighlightO_LILhx2 is expressed in germ cells of developing mouse testis but is dispensable for germ cell and Sertoli cell specification C_LIO_LILoss of Lhx2 disrupts testicular vascularization, leads to the expansion of interstitial cells, and alters the tubular organization C_LIO_LIGerm cells govern the tubular organization in the developing testis C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/522214v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1a1761dorg.highwire.dtl.DTLVardef@1519f12org.highwire.dtl.DTLVardef@1a263baorg.highwire.dtl.DTLVardef@4167f2_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

Maximization of Energy Recovery from Starch Processing Wastewater by Thermophilic Dark Fermentation Coupled with Microbial fuel Cell Technology

Utilization of organic wastewater for hydrogen production has dual advantages of clean energy generation and bioremediation which is sustainable for a longer period. To maximize the energy recovery from starch rich wastewater, a two stage system comprising of thermophilic dark fermentation coupled with microbial fuel cell was employed. A single parameter optimization strategy was implemented for the operation of the batch system. The maximum cumulative hydrogen production obtained was 2.56 L L-1 with a 48 % reduction in COD under the optimal conditions of 35 g L-1 initial substrate concentration (COD), temperature 60 oC, and pH 6.5. The H2 yield and H2 production rate were 6.8 mol H2/kg CODreduced and 731.3 mL L-1 h-1 respectively. The effect of the organic loading rate (OLR) on H2 production rate was studied in a continuous stirred tank reactor (CSTR). A maximum hydrogen production rate of 913 mL L-1 h-1 was observed at an OLR of 5.6 g L- 1 h-1. Effluent recycle played an important role in the improvement of H2 production. A maximum H2 production rate of 1224 mL L-1 h-1 was observed at a recycle ratio of 0.6. Power density of 4.2 W m-3 was observed with MFC using the dark fermentative spent media neutralized with carbonate buffer at an optimal pH of 7. A total COD reduction of 86% was observed.

bioengineering↗

bioRxiv2022

A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites

Malaria parasites avoid immune clearance through their ability to systematically alter antigens exposed on the surface of infected red blood cells. This is accomplished by tightly regulated transcriptional control of individual members of a large, multicopy gene family called var and is the key to both the virulence and chronic nature of malaria infections. Expression of var genes is mutually exclusive and controlled epigenetically, however how large populations of parasites coordinate var gene switching to avoid premature exposure of the antigenic repertoire is unknown. Here we provide evidence for a transcriptional network anchored by a universally conserved gene called var2csa that coordinates the switching process. We describe a structured switching bias that shifts overtime and could shape the pattern of var expression over the course of a lengthy infection. Our results provide an explanation for a previously mysterious aspect of malaria infections and shed light on how parasites possessing a relatively small repertoire of variant antigen encoding genes can coordinate switching events to limit antigen exposure, thereby maintaining chronic infections.

microbiology↗

bioRxiv2022

Potentiation of Adipogenesis by Reactive Oxygen Species is a Unifying Mechanism in the Pro-adipogenic Properties of Bisphenol A and its New Structural Analogues.

AimsStructural analogues of bisphenol A (BPA), including BPS and BPF, are emerging environmental toxicants as their presence in the environment is rising since new regulatory restrictions were placed on BPA-containing infant products. The adipogenesis-enhancing effect of bisphenols may explain the link between human exposure and metabolic disease; however, underlying molecular pathways remain unresolved. ResultsExposure to BPS, BPF, BPA or ROS generators enhanced lipid droplet formation and expression of adipogenic markers after induction of differentiation in adipose-derived progenitors isolated from mice. RNAseq analysis in BPS-exposed progenitors revealed modulation in pathways regulating adipogenesis and responses to oxidative stress. ROS was higher in bisphenol-exposed cells, while co-treatment with antioxidants attenuated adipogenesis and abolished the effect of BPS. There was a loss of mitochondria membrane potential in BPS-exposed cells and mitochondria-derived ROS contributed to potentiation of adipogenesis by BPS and its analogues. Male mice exposed to BPS during gestation had higher whole-body adiposity, as measured by TD-NMR, while postnatal exposure had no impact on adiposity in either sex. InnovationThese findings support existing evidence showing a role for ROS in regulating adipocyte differentiation and are the first to highlight ROS as a unifying mechanism that explains the pro-adipogenic properties of BPA and its structural analogues. ConclusionROS act as signaling molecules in the regulation of adipocyte differentiation and mediate bisphenol-induced potentiation of adipogenesis.

molecular biology↗

bioRxiv2022

Using axenic and gnotobiotic insects to examine the role of different microbes on the development and reproduction of the kissing bug Rhodnius prolixus (Hemiptera: Reduviidae)

Kissing bugs (Hempitera: Reduviidae) are obligately and exclusively blood feeding insects. Vertebrate blood is thought to provide insufficient B vitamins to insects, which rely on obligate symbiotic relationships with bacteria that provision these nutrients. Kissing bugs harbor environmentally acquired bacteria in their gut lumen, without which they are unable to develop to adulthood. Early experiments identified a single bacterial species, Rhodococcus rhodnii, as a symbiont of Rhodnius prolixus, but modern studies of the kissing bug microbiome suggest that R. rhodnii is not always present or abundant in wild-caught individuals. We asked whether R. rhodnii or other bacteria alone could function as symbionts of R. prolixus. Bacteria-free (axenic) insects were produced whose microbiome could be experimentally manipulated to produce insects with known microbiomes (gnotobiotic). We found that gnotobiotic insects harboring R. rhodnii alone developed faster, had higher survival, and laid more eggs than gnotobiotic R. prolixus harboring other bacterial monocultures, including other described symbionts of kissing bugs and several related Rhodococcus species. R. rhodnii grew to high titer in the guts of R. prolixus while other tested species were found at much lower abundance. Rhodococcus species tested had nearly identical B vitamin biosynthesis genes, and dietary supplementation of B vitamins had a relatively minor effect on development and survival of gnotobiotic R. prolixus. Our results indicate that R. prolixus have a higher fitness when harboring R. rhodnii than other bacteria tested, and that symbiont B vitamin synthesis is likely a necessary but not sufficient function of gut bacteria in kissing bugs.

microbiology↗

bioRxiv2022

PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression

Autosomal dominant polycystic kidney disease (ADPKD), among the most common human genetic conditions and a frequent etiology of kidney failure, is primarily caused by heterozygous PKD1 mutations. Kidney cyst formation ensues when the PKD1 dosage falls below a critical threshold. However, no framework exists to harness the remaining allele or reverse PKD1 decline. Here, we show that mRNAs produced by the noninactivated PKD1 allele are cis-repressed via their 3-UTR miR-17 binding element. Eliminating this motif (Pkd1{Delta}17) improves mRNA stability, raises Polycystin-1 levels, and alleviates cyst growth in cellular, ex vivo, and mouse PKD models. Remarkably, Pkd2 is also autoinhibited via its 3-UTR miR-17 motif, and Pkd2{Delta}17-induced Polycystin-2 derepression partly compensates and retards cyst growth in Pkd1-mutant models. Moreover, acutely blocking Pkd1/2 cis-inhibition, including after cyst onset, attenuates murine PKD. Finally, PKD1{Delta}17 or PKD2{Delta}17 alleles revert cyst-pathogenic sequala in patient-derived primary ADPKD cultures. Thus, evading 3-UTR cis-interference and enhancing PKD1/2 mRNA translation is a potentially mutation-agnostic ADPKD-arresting approach.

genetics↗

bioRxiv2021

Enhancer and super-enhancer landscape in polycystic kidney disease

Widespread aberrant gene expression is pathological hallmark of polycystic kidney disease (PKD). Numerous pathogenic signaling cascades, including c-Myc, Fos, and Jun are transactivated. However, the underlying epigenetic regulators are poorly defined. Here we show that H3K27ac, a histone modification that marks active enhancers, is elevated in mouse and human ADPKD samples. Using comparative H3K27ac ChIP-Seq analysis, we mapped >16000 active intronic and intergenic enhancer elements in Pkd1-mutant mouse kidneys. We find that the cystic kidney epigenetic landscape resembles that of a developing kidney, and >90% of upregulated genes in Pkd1-mutant kidneys are co-housed with activated enhancers in the same topologically associated domains. Furthermore, we identify an evolutionarily-conserved enhancer cluster downstream of the c-Myc gene and super-enhancers flanking both Jun and Fos loci in mouse and human ADPKD models. Deleting these regulatory elements reduces c-Myc, Jun, or Fos abundance and suppresses proliferation and 3D cyst growth of Pkd1-mutant cells. Finally, inhibiting glycolysis and glutaminolysis or activating Ppara in Pkd1-mutant cells lowers global H3K27ac levels and on c-Myc enhancers. Thus, our work suggests that epigenetic rewiring mediates the transcriptomic dysregulation in PKD, and the regulatory elements can be targeted to slow cyst growth.

molecular biology↗

bioRxiv2021

Adaptation and Compensation in a Bacterial Gene Regulatory Network Evolving Under Antibiotic Selection

Gene regulatory networks allow organisms to generate coordinated responses to environmental challenges. In bacteria, regulatory networks are re-wired and re-purposed during evolution, though the relationship between selection pressures and evolutionary change is poorly understood. In this study, we discover that early evolutionary response of Escherichia coli to the antibiotic trimethoprim involves de-repression of PhoPQ signalling, a Mg2+-sensitive two-component system, by inactivation of the MgrB feedback-regulatory protein. We report that de-repression of PhoPQ confers trimethoprim-tolerance to E. coli by hitherto unrecognized transcriptional up-regulation of dihydrofolate reductase (DHFR), target of trimethoprim. As a result, mutations in mgrB precede and facilitate the evolution of drug resistance. Using laboratory evolution, genome sequencing and mutation re-construction, we show that populations of E. coli challenged with trimethoprim are faced with the evolutionary choice of transitioning from tolerant to resistant by mutations in DHFR, or compensating for the fitness costs of PhoPQ de-repression by inactivating the RpoS sigma factor, itself a PhoPQ-target. Outcomes at this evolutionary branch-point are determined by strength of antibiotic selection, such that high pressures favour resistance, while low pressures favour cost-compensation. Our results relate evolutionary changes in bacterial gene regulatory networks to strength of selection and provide mechanistic evidence to substantiate this link.

microbiology↗

bioRxiv2021

Epigenetic reprogramming ameliorates type 1 diabetes by decreasing the generation of Th1 and Th17 subsets and restoring self-tolerance in CD4+ T cells

The histone modifier Trichostatin A (TSA) ameliorated diabetes and repressed IFN-{gamma} and IL-17A expression in prediabetic female NOD mice. Purified CD4+ cells could be polarized ex vivo into Th1 and Th17 subsets, which comparably transferred diabetes into NOD.scid mice. Polarized Th1 cells were devoid of IL-17A-producing cells and did not transdifferentiate into Th17 cells in an immunodeficient environment. However, Th17 cells had contaminant Th1 cells, which expressed IFN-{gamma} upon adoptive transfer into lymphopenic recipients. Notably, TSA treatment abrogated the transfer of diabetes by CD4+ T-cells cultured under Th1 or Th17 polarizing conditions accompanied by the absence of Ifng and Il17a expression in NOD.scid recipients. Significantly, the histone modifier restored the ability of CD4+ but not CD8+ T-cells to undergo CD3-mediated apoptosis ex vivo in a caspase-dependent manner. Thus, the histone modifier afforded protection against autoimmune diabetes by negative regulation of signature lymphokines and restitution of self-tolerance in CD4+ T cells.

immunology↗

bioRxiv2021

Improved HIV-1 drug resistance mutation prediction using quasispecies reconstruction supported analysis

Accurate and sensitive approaches to detect HIV-1 drug resistance mutations (DRMs) are indispensable for the paradigm of treatment as prevention. While HIV-1 proviral DNA allows sensitive high throughput sequencing (HTS)-based DRM detection, its applicability is limited by presence of defective genomes. This study demonstrates application of quasispecies reconstruction algorithms (QRAs) to improve DRM detection sensitivity from proviral DNA. A robust benchmarking of 5 QRAs was performed with 2 distinct experimental control-datasets including a stringent, novel control: DCPM, simulating in-vivo variant distribution (0.08%-86.5%). Selected QRA was further evaluated for its ability to differentiate DRMs from hypermutated sequences using an in-silico control. PredictHaplo outperformed all others in terms of precision and was selected for further analysis. Near full-genome HTS was performed on proviral DNA from 20 HIV-1C infected individuals, at different stages of ART, from Mumbai, India. DRM detection was performed through residue-wise variation analysis and implementation of QRAs. Both analyses were highly concordant for DRM frequencies >10% (spearman r=0.91, p<0.0001). Phylogenetic association in HTS datasets with shared transmission history could also be demonstrated by PredictHaplo. This study highlights utility of QRAs as an adjunct to traditional residue-wise variation-based DRM detection leading to optimal personalized ART as well as better disease management.

bioinformatics↗

bioRxiv2020

The evolutionary dynamics of genetic incompatibilities introduced by duplicated genes in Arabidopsis thaliana

Although gene duplications provide genetic backup and allow genomic changes under relaxed selection, they may potentially limit gene flow. When different copies of a duplicated gene are pseudo-functionalized in different genotypes, genetic incompatibilities can arise in their hybrid offspring. While such cases have been reported after manual crosses, it remains unclear whether they occur in nature and how they affect natural populations. Here we identified four duplicated-gene based incompatibilities including one previously not reported within an artificial Arabidopsis intercross population. Unexpectedly, however, for each of the genetic incompatibilities we also identified the incompatible alleles in natural populations based on the genomes of 1,135 Arabidopsis accessions published by the 1001 Genomes Project. Using the presence of incompatible allele combinations as phenotypes for GWAS, we mapped genomic regions which included additional gene copies which likely rescue the genetic incompatibility. Reconstructing the geographic origins and evolutionary trajectories of the individual alleles suggested that incompatible alleles frequently co-exist, even in geographically closed regions, and that their effects can be overcome by additional gene copies collectively shaping the evolutionary dynamics of duplicated genes during population history.

evolutionary biology↗

bioRxiv2020

Geospatial HIV-1 subtype C gp120 sequence diversity and its predicated impact on broadly neutralizing antibody sensitivity

Evolving diversity in globally circulating HIV-1 subtypes presents formidable challenge in defining and developing neutralizing antibodies for prevention and treatment. HIV-1 subtype C is responsible for majority of global HIV-1 infections. Broadly neutralizing antibodies (bnAbs) capable of neutralizing distinct HIV-1 subtypes by targeting conserved vulnerable epitopes on viral envelope protein (Env) are being considered as promising antiviral agents for prevention and treatment. In the present study, we examined the diversity in genetic signatures and attributes that differentiate region-specific global HIV-1 subtype C gp120 sequences associated with virus neutralization outcomes to key bnAbs having distinct epitope specificities. A total of 1814 full length HIV-1 subtype C gp120 sequence from 37 countries were retrieved from Los Alamos National Laboratory HIV database (www.hiv.lanl.gov). The amino acid sequences were assessed for their phylogenetic association, variable loop lengths and prevalence of potential N-linked glycosylation sites (pNLGS). Responses of these sequences to bnAbs were predicted with a machine learning algorithm bNAb-ReP and compared with those reported in the CATNAP database. Phylogenetically, sequences from Asian countries including India clustered together however differed significantly when compared with pan African subtype C sequences. Variable loop lengths within Indian and African clusters were distinct from each other, specifically V1, V2 and V4 loops. Furthermore, V1V2 and V2 alone sequences were also found to vary significantly in their charges. Pairwise analyses at each of the 25 pNLG sites indicated distinct country specific profiles. Highly significant differences (p<0.001***) were observed in prevalence of four pNLGS (N130, N295, N392 and N448) between South Africa and India, having most disease burden associated with subtype C. Our findings highlight that the distinctly evolving clusters within global intra-subtype C gp120 sequences are likely to influence the disparate region-specific sensitivity of circulating HIV-1 subtype C to bnAbs.

bioinformatics↗

bioRxiv2019

The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm

Piwi-interacting RNAs (piRNAs) and PIWI proteins are essential in germ cells to repress transposons and regulate mRNAs. In Drosophila, piRNAs bound to the PIWI protein Aubergine (Aub) are transferred maternally to the embryo and regulate maternal mRNA stability through two opposite roles. They target mRNAs by incomplete base-pairing, leading to both their destabilization in the soma, and stabilization in the germ plasm. Here, we report a function of Aub in translation. Aub is required for translational activation of nanos mRNA, a key determinant of the germ plasm. Aub physically interacts with the poly(A) binding protein PABP and the translation initiation factor eIF3. Polysome gradient profiling identifies Aub role at the initiation step of translation. In the germ plasm, PABP and eIF3d assemble in foci that surround Aub-containing germ granules, and Aub acts with eIF3d to promote nanos translation. These results reveal a new mode of mRNA regulation by Aub, highlighting PIWI protein versatility in mRNA regulation.

developmental biology↗

bioRxiv2019

Integrated RNA and metabolite profiling of urine liquid biopsies for prostate cancer biomarker discovery

Sensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible \"liquid biopsies\". Herein we used urine liquid biopsies to identify and characterize a novel group of urine-enriched RNAs and metabolites in PCa patients and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. The mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supports a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in prostate cancer, which can be exploited for novel biomarkers and therapies.

cancer biology↗

bioRxiv2019

The CNS in the face of ART contains T cell origin HIV which can lead to drug resistance

HIV persists despite antiretroviral therapy (ART) in cellular reservoirs thought to occur in distinct anatomical compartments. Therapy failure may occur because of incomplete ART adherence and possibly viral replication at some reservoir sites. The CNS may serve as a reservoir site due to lowered ART penetration and virus production from long-lived tissue resident macrophages. Compelling evidence for the CNS as a reservoir is the existence of individuals where HIV is suppressed below limit of detection in blood but detectable in the cerebrospinal fluid (CSF), termed CSF Escape. Here, we asked whether HIV in CSF Escape individuals is derived from macrophages or persists due to lowered ART. We used cell surface markers on the HIV envelope to determine the cellular source of HIV. We verified detection using in vitro derived virus from infected macrophages and T cells and tested CSF from CSF Escape individuals. We observed host surface markers consistent with T cell origin. We also measured ART concentrations in the CSF and plasma. We found a dramatic decrease in CSF ART concentrations described previously, but no significant difference between CSF Escape versus fully suppressed individuals. To examine the effect of the observed CSF ART concentrations on HIV replication, we used long-term infection with ART in cell culture. CSF Escape ART levels led to either HIV suppression or evolution of drug resistance, but not replication of drug sensitive HIV. These observations argue that persistent CNS viremia despite ART can be T cell generated and may result in drug resistance and therapy failure.

microbiology↗

bioRxiv2019

A real-time PCR for the differentiation of typhoidal and non-typhoidal Salmonella

Rapid and accurate differentiation of Salmonella spp. causing enteric fever from non-typhoidal Salmonella is essential for clinical management of cases, laboratory risk management and implementation of public health measures. Current methods used for confirmation of identification including biochemistry and serotyping as well as whole genome sequencing analyses, takes several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies, for the rapid identification of typhoidal and non-typhoidal Salmonella. This novel two-hour assay identifies the genus Salmonella by detecting the ttr gene, encoding tetrathionate reductase, and defines typhoidal Salmonella by the detection of S. Typhi and Paratyphi-specific gene combinations. PCR assay performance was determined using 211 clinical cultures of Salmonella (114 non-typhoidal and 97 Typhoidal strains) and 7 clinical non-Salmonella cultures. In addition, the specificity of the assay was evaluated in silico using a diverse in-house collection of 1882 Salmonella whole genome sequences. The real-time PCR results for 218 isolates and the genomic analysis of the 1882 isolates produced 100% sensitivity and 100% specificity (based on a 7 gene profile) for identifying typhoidal Salmonella compared to the Salmonella whole genome sequening identification methods currently used at Public Health England. This paper describes a robust real-time PCR assay for the rapid, accurate identification of typhoidal and non-typhoidal Salmonella which will be invaluable for the urgent screening of isolates from symptomatic individuals, the safe processing of isolates in laboratories and for assisting the management of public health risks.

microbiology↗