scholarly journals Machine learning identifies signatures of host adaptation in the bacterial pathogen Salmonella enterica

2017 ◽  
Author(s):  
Nicole E. Wheeler ◽  
Paul P. Gardner ◽  
Lars Barquist
Keyword(s):  
Random Forest ◽  
Host Range ◽  
Salmonella Enterica ◽  
Bacterial Pathogen ◽  
Host Adaptation ◽  
Random Forest Classifier ◽  
Sub Saharan Africa ◽  
Broad Host Range ◽  
Invasive Infection ◽  
Emerging Pathogens

AbstractEmerging pathogens are a major threat to public health, however understanding how pathogens adapt to new niches remains a challenge. New methods are urgently required to provide functional insights into pathogens from the massive genomic data sets now being generated from routine pathogen surveillance for epidemiological purposes. Here, we measure the burden of atypical mutations in protein coding genes across independently evolved Salmonella enterica lineages, and use these as input to train a random forest classifier to identify strains associated with extraintestinal disease. Members of the species fall along a continuum, from pathovars which cause gastrointestinal infection and low mortality, associated with a broad host-range, to those that cause invasive infection and high mortality, associated with a narrowed host range. Our random forest classifier learned to perfectly discriminate long-established gastrointestinal and invasive serovars of Salmonella. Additionally, it was able to discriminate recently emerged Salmonella Enteritidis and Typhimurium lineages associated with invasive disease in immunocompromised populations in sub-Saharan Africa, and within-host adaptation to invasive infection. We dissect the architecture of the model to identify the genes that were most informative of phenotype, revealing a common theme of degradation of metabolic pathways in extraintestinal lineages. This approach accurately identifies patterns of gene degradation and diversifying selection specific to invasive serovars that have been captured by more labour-intensive investigations, but can be readily scaled to larger analyses.

scholarly journals Cooperation of Adhesin Alleles in Salmonella-Host Tropism

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Leon De Masi ◽  
Min Yue ◽  
Changmin Hu ◽  
Alexey V. Rakov ◽  
Shelley C. Rankin ◽  
...  
Keyword(s):  
Host Range ◽  
Salmonella Enterica ◽  
Bacterial Pathogen ◽  
The United States ◽  
Host Adaptation ◽  
Broad Host Range ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Contaminated Food ◽  
Colonization Factors

ABSTRACT Salmonella enterica remains a leading foodborne bacterial pathogen in the United States; infected livestock serve often as the source of contaminated food products. A study estimated that over a billion Salmonella gastroenteritis cases and up to 33 million typhoid cases occur annually worldwide, with 3.5 million deaths. Although many Salmonella strains with a broad host range present preferential associations with certain host species, it is not clear what determines the various levels of host adaptation. Here, causal properties of host associations were determined with allelic variants of three colonization factors of S. enterica serovar Newport, a most frequent zoonotic serovar. This is the first study that related not only individual but also a small group of host-associated gene variants with functional properties that cooperate to determine the level of host-adapted virulence. The detected associations should help to identify sources of Salmonella infections in both humans and animals. Allelic combinations and host specificities for three fimbrial adhesins, FimH, BcfD, and StfH, were compared for 262 strains of Salmonella enterica serovar Newport, a frequent human and livestock pathogen. Like FimH, BcfD had two major alleles (designated A and B), whereas StfH had two allelic groups, each with two alleles (subgroup A1 and A2 and subgroup B1 and B2). The most prevalent combinations of FimH/BcfD/StfH alleles in S. Newport were A/A/A1 and B/B/B1. The former set was most frequently found in bovine and porcine strains, whereas the latter combination was most frequently found in environmental and human isolates. Bacteria genetically engineered to express Fim, Bcf, or Stf fimbriae on their surface were tested with the different alleles for binding to human, porcine, and bovine intestinal epithelial cells. The major allelic combinations with bovine and porcine strains (A/A/A1) or with human isolates (B/B/B1) provided at least two alleles capable of binding significantly better than the other alleles to an intestinal epithelial cell line from the respective host(s). However, each combination of alleles kept at least one allele mediating binding to an intestinal epithelial cell from another host. These findings indicated that allelic variation in multiple adhesins of S. Newport contributes to bacterial adaptation to certain preferential hosts without losing the capacity to maintain a broad host range. IMPORTANCE Salmonella enterica remains a leading foodborne bacterial pathogen in the United States; infected livestock serve often as the source of contaminated food products. A study estimated that over a billion Salmonella gastroenteritis cases and up to 33 million typhoid cases occur annually worldwide, with 3.5 million deaths. Although many Salmonella strains with a broad host range present preferential associations with certain host species, it is not clear what determines the various levels of host adaptation. Here, causal properties of host associations were determined with allelic variants of three colonization factors of S. enterica serovar Newport, a most frequent zoonotic serovar. This is the first study that related not only individual but also a small group of host-associated gene variants with functional properties that cooperate to determine the level of host-adapted virulence. The detected associations should help to identify sources of Salmonella infections in both humans and animals.

scholarly journals Development of the Automated Primer Design Workflow Uniqprimer and Diagnostic Primers for the Broad-Host-Range Plant Pathogen Dickeya dianthicola

Plant Disease ◽  
2019 ◽  
Vol 103 (11) ◽  
pp. 2893-2902 ◽  
Author(s):  
Shaista Karim ◽  
R. Ryan McNally ◽  
Afnan S. Nasaruddin ◽  
Alexis DeReeper ◽  
Ramil P. Mauleon ◽  
...  
Keyword(s):  
Host Range ◽  
Bacterial Pathogen ◽  
The United States ◽  
Broad Host Range ◽  
Software Pipeline ◽  
Widespread Occurrence ◽  
Field Samples ◽  
Primer Sets ◽  
Genome Analyses ◽  
User Friendly

Uniqprimer, a software pipeline developed in Python, was deployed as a user-friendly internet tool in Rice Galaxy for comparative genome analyses to design primer sets for PCRassays capable of detecting target bacterial taxa. The pipeline was trialed with Dickeya dianthicola, a destructive broad-host-range bacterial pathogen found in most potato-growing regions. Dickeya is a highly variable genus, and some primers available to detect this genus and species exhibit common diagnostic failures. Upon uploading a selection of target and nontarget genomes, six primer sets were rapidly identified with Uniqprimer, of which two were specific and sensitive when tested with D. dianthicola. The remaining four amplified a minority of the nontarget strains tested. The two promising candidate primer sets were trialed with DNA isolated from 116 field samples from across the United States that were previously submitted for testing. D. dianthicola was detected in 41 samples, demonstrating the applicability of our detection primers and suggesting widespread occurrence of D. dianthicola in North America.

scholarly journals Diversity and Host Specificity Revealed by Biological Characterization and Whole Genome Sequencing of Bacteriophages Infecting Salmonella enterica

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 854 ◽  
Author(s):  
Fong ◽  
Tremblay ◽  
Delaquis ◽  
Goodridge ◽  
Levesque ◽  
...  
Keyword(s):  
Host Range ◽  
Salmonella Enterica ◽  
Nucleotide Identity ◽  
Comparative Genomic ◽  
Broad Host Range ◽  
Natural Environments ◽  
Host Interactions ◽  
Knowledge Framework ◽  
Isolation And Characterization ◽  
Opportunistic Human Pathogen

Phages infecting members of the opportunistic human pathogen, Salmonella enterica, are widespread in natural environments and offer a potential source of agents that could be used for controlling populations of this bacterium; yet, relatively little is known about these phages. Here we describe the isolation and characterization of 45 phages of Salmonella enterica from disparate geographic locations within British Columbia, Canada. Host-range profiling revealed host-specific patterns of susceptibility and resistance, with several phages identified that have a broad-host range (i.e., able to lyse >40% of bacterial hosts tested). One phage in particular, SE13, is able to lyse 51 out of the 61 Salmonella strains tested. Comparative genomic analyses also revealed an abundance of sequence diversity in the sequenced phages. Alignment of the genomes grouped the phages into 12 clusters with three singletons. Phages within certain clusters exhibited extraordinarily high genome homology (>98% nucleotide identity), yet between clusters, genomes exhibited a span of diversity (<50% nucleotide identity). Alignment of the major capsid protein also supported the clustering pattern observed with alignment of the whole genomes. We further observed associations between genomic relatedness and the site of isolation, as well as genetic elements related to DNA metabolism and host virulence. Our data support the knowledge framework for phage diversity and phage–host interactions that are required for developing phage-based applications for various sectors, including biocontrol, detection and typing.

scholarly journals Emergence and Spread of Different ESBL-Producing Salmonella enterica Serovars in Hospitalized Horses Sharing a Highly Transferable IncM2 CTX-M-3-Encoding Plasmid

2020 ◽  
Vol 11 ◽  
Author(s):  
Ziv Dor ◽  
Anat Shnaiderman-Torban ◽  
Kira Kondratyeva ◽  
Maya Davidovich-Cohen ◽  
Assaf Rokney ◽  
...  
Keyword(s):  
Host Range ◽  
Salmonella Enterica ◽  
Meta Analysis ◽  
Health Hazard ◽  
Companion Animals ◽  
Antibiotic Resistance Genes ◽  
Complete Sequence ◽  
Control Measures ◽  
Health Concern ◽  
Broad Host Range

Salmonella enterica is a major causative pathogen of human and animal gastroenteritis. Antibiotic resistant strains have emerged due to the production of extended-spectrum β-lactamases (ESBLs) posing a major health concern. With the increasing reports on ESBL-producing Enterobacterales that colonize companion animals, we aimed to investigate ESBL dissemination among ESBL-producing Salmonella enterica (ESBL-S) in hospitalized horses. We prospectively collected ESBL-S isolates from hospitalized horses in a Veterinary-Teaching Hospital during Dec 2015–Dec 2017. Selection criteria for ESBL-S were white colonies on CHROMagarESBL plates and an ESBL phenotypic confirmation. Salmonella enterica serovars were determined using the Kaufmann-White-Le-Minor serological scheme. ESBL-encoding plasmids were purified, transformed and compared using restriction fragment length polymorphism (RFLP). Whole genome sequencing (Illumina and MinION platforms) were performed for detailed phylogenetic and plasmid analyses. Twelve ESBL-S were included in this study. Molecular investigation and Sequence Read Archive (SRA) meta-analysis revealed the presence of three unique Salmonella enterica serovars, Cerro, Havana and Liverpool, all reported for the first time in horses. PFGE revealed the clonal spread of S. Cerro between seven horses. All twelve isolates carried blaCTX–M–3 and showed an identical multidrug resistance profile with co-resistance to trimethoprim/sulfamethoxazole and to aminoglycosides. Plasmid RFLP proved the inter-serovar horizontal spread of a single blaCTX–M–3-encoding plasmid. Complete sequence of a representative plasmid (S. Havana strain 373.3.1), designated pSEIL-3 was a -86.4 Kb IncM2 plasmid, that encoded nine antibiotic resistance genes. pSEIL-3 was virtually identical to pCTX-M3 from Citrobacter freundii, and showed high identity (&gt;95%) to six other blaCTX–M–3 or blaNDM–1 IncM2 broad host range plasmids from various Enterobacterales of human origin. Using a specific six gene-based multiplex PCR, we detected pSEIL-3 in various Enterobacterales species that co-colonized the horses’ gut. Together, our findings show the alarming emergence of ESBL-S in hospitalized horses associated with gut shedding and foal morbidity and mortality. We demonstrated the dissemination of CTX-M-3 ESBL among different Salmonella enterica serovars due to transmission of a broad host range plasmid. This report highlights horses as a zoonotic reservoir for ESBL-S, including highly transmissible plasmids that may represent a ‘One-Health’ hazard. This risk calls for the implementation of infection control measures to monitor and control the spread of ESBL-S in hospitalized horses.

scholarly journals Evolution of Salmonella enterica serotype Typhimurium driven by anthropogenic selection and niche adaptation

2019 ◽  
Author(s):  
Matt Bawn ◽  
Gaetan Thilliez ◽  
Mark Kirkwood ◽  
Nicole Wheeler ◽  
Liljana Petrovska ◽  
...  
Keyword(s):  
Host Range ◽  
Salmonella Enterica ◽  
Genotypic Variation ◽  
Avian Species ◽  
Whole Genome Sequence ◽  
Broad Host Range ◽  
Niche Adaptation ◽  
Disseminated Disease ◽  
Distinct Distribution ◽  
Anthropogenic Selection

AbstractSalmonella enterica serotype Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and disseminated disease worldwide. Two S. Typhimurium strains (SL1344 and ATCC14028) are widely used to study host-pathogen interactions, yet genotypic variation results in strains with diverse host range, pathogenicity and risk to food safety. A robust fully parsimonious phylogenetic tree constructed from recombination purged variation in the whole genome sequence of 131 diverse strains of S. Typhimurium revealed population structure composed of two high order clades (α and β) and multiple subclades on extended internal branches, that exhibited distinct signatures of host adaptation and anthropogenic selection. Clade α contained a number of subclades composed of strains from well characterized epidemics in domesticated animals, while clade β predominantly contained subclades associated with wild avian species, with the notable exception of a subclade containing the DT204/49 complex. The contrasting epidemiology of α and β strains was reflected in a distinct distribution of antimicrobial resistance (AMR) genes, accumulation of hypothetically disrupted coding sequences (HDCS), and signatures of functional diversification associated with invasiveness of host adapted serotypes. Gene flux was predominantly driven by acquisition, loss or recombination of prophage. The acquisition of large genetic islands (SGI-1 and 4) was limited to two recent pandemic clones (DT104 and monophasic S. Typhimurium ST34) in clade α. Together, our data are consistent with the view that a broad host range common ancestor of S. Typhimurium diversified with clade α lineages remained largely associated with multiple domesticated animal species, while clade β spawned multiple lineages that underwent diversifying selection associated with adaptation to various niches, predominantly in wild avian species.

scholarly journals Salmonella enterica Serovar Typhi Possesses a Unique Repertoire of Fimbrial Gene Sequences

2001 ◽  
Vol 69 (5) ◽  
pp. 2894-2901 ◽  
Author(s):  
Stacy M. Townsend ◽  
Naomi E. Kramer ◽  
Robert Edwards ◽  
Stephen Baker ◽  
Nancy Hamlin ◽  
...  
Keyword(s):  
Host Range ◽  
Salmonella Enterica ◽  
Host Adaptation ◽  
Unique Combination ◽  
Gene Sequences ◽  
Simple Correlation ◽  
Salmonella Enterica Serovar Typhi ◽  
Type Iv ◽  
Reference Collection ◽  
First Time

ABSTRACT Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes by its strict host adaptation to humans and higher primates. Since fimbriae have been implicated in host adaptation, we investigated whether the serotype Typhi genome contains fimbrial operons which are unique to this pathogen or restricted to typhoidal Salmonella serotypes. This study established for the first time the total number of fimbrial operons present in an individual Salmonella serotype. The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly class. In addition tosef, fim, saf, and tcf, which had been described previously in serotype Typhi, we identified eight new putative chaperone-usher-dependent fimbrial operons, which were termedbcf, sta, stb, ste, std, stc, stg, and sth. Hybridization analysis performed with 16 strains ofSalmonella reference collection C and 22 strains ofSalmonella reference collection B showed that all eight putative fimbrial operons of serotype Typhi were also present in a number of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host range and the presence of a single fimbrial operon seems at present unlikely. However, the serotype Typhi genome differed from that of all other Salmonella serotypes investigated in that it contained a unique combination of putative fimbrial operons.

scholarly journals Host Restriction of Salmonella enterica Serotype Typhimurium Pigeon Isolates Does Not Correlate with Loss of Discrete Genes

2004 ◽  
Vol 186 (9) ◽  
pp. 2619-2628 ◽  
Author(s):  
Helene L. Andrews-Polymenis ◽  
Wolfgang Rabsch ◽  
Steffen Porwollik ◽  
Michael McClelland ◽  
Carlos Rosetti ◽  
...  
Keyword(s):  
Host Range ◽  
Dna Microarray ◽  
Salmonella Enterica ◽  
Broad Host Range ◽  
Fluid Accumulation ◽  
Host Restriction ◽  
Phage Types ◽  
Chromosomal Genes ◽  
Large Groups ◽  
Intestinal Persistence

ABSTRACT The definitive phage types (DT) 2 and 99 of Salmonella enterica serotype Typhimurium are epidemiologically correlated with a host range restricted to pigeons, in contrast to phage types with broader host ranges such as epidemic cattle isolates (DT104 and DT204). To determine whether phage types with broad host range possess genetic islands absent from host-restricted phage types, we compared the genomes of four pigeon isolates to serotype Typhimurium strain LT2 using a DNA microarray. Three of the four isolates tested caused fluid accumulation in bovine ligated ileal loops, but they had reduced colonization of liver and spleen in susceptible BALB/c mice and were defective for intestinal persistence in Salmonella-resistant CBA mice. The genomes of the DT99 and DT2 isolates were extremely similar to the LT2 genome, with few notable differences on the level of complete individual genes. Two large groups of genes representing the Fels-1 and Fels-2 prophages were missing from the DT2 and DT99 phage types we analyzed. One of the DT99 isolates examined was lacking a third cluster of five chromosomal genes (STM1555 to -1559). Results of the microarray analysis were extended using Southern analysis to a collection of 75 serotype Typhimurium clinical isolates of 24 different phage types. This analysis revealed no correlation between the presence of Fels-1, Fels-2, or STM1555 to -1559 and the association of phage types with different host reservoirs. We conclude that serotype Typhimurium phage types with broad host range do not possess genetic islands influencing host restriction, which are absent from the host-restricted pigeon isolates.

scholarly journals Salmonella enterica Serovar Enteritidis Core O Polysaccharide Conjugated to H:g,m Flagellin as a Candidate Vaccine for Protection against Invasive Infection withS.Enteritidis

2011 ◽  
Vol 79 (10) ◽  
pp. 4240-4249 ◽  
Author(s):  
Raphael Simon ◽  
Sharon M. Tennant ◽  
Jin Y. Wang ◽  
Patrick J. Schmidlein ◽  
Andrew Lees ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
The Elderly ◽  
Sub Saharan Africa ◽  
Invasive Infection ◽  
Salmonella Enterica Serovar Enteritidis ◽  
Lethal Challenge ◽  
Content Type ◽  
Protective Antigens ◽  
Flagellar Proteins ◽  
Sub Saharan

ABSTRACTNontyphoidalSalmonella entericaserovars Enteritidis and Typhimurium are a common cause of gastroenteritis but also cause invasive infections and enteric fever in certain hosts (young children in sub-Saharan Africa, the elderly, and immunocompromised individuals).SalmonellaO polysaccharides (OPS) and flagellar proteins are virulence factors and protective antigens. The surface polysaccharides ofSalmonellaare poorly immunogenic and do not confer immunologic memory, limitations overcome by covalently attaching them to carrier proteins. We conjugated core polysaccharide-OPS (COPS) ofSalmonellaEnteritidis lipopolysaccharide (LPS) to flagellin protein from the homologous strain. COPS and flagellin were purified from a genetically attenuated (ΔguaBA) “reagent strain” (derived from an isolate from a patient with clinical bacteremia) engineered for increased flagellin production (ΔclpPX). Conjugates were constructed by linking flagellin monomers or polymers at random COPS hydroxyls with various polysaccharide/protein ratios by 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) or at the 3-deoxy-d-manno-octulosonic acid (KDO) terminus by thioether chemistry. Mice immunized on days 0, 28, and 56 with COPS-flagellin conjugates mounted higher anti-LPS IgG levels than mice receiving unconjugated COPS and exhibited high antiflagellin IgG; anti-LPS and antiflagellin IgG levels increased following booster doses. Antibodies generated by COPS-flagellin conjugates mediated opsonophagocytosis ofS.Enteritidis cells into mouse macrophages. Mice immunized with flagellin alone, COPS-CRM197, or COPS-flagellin conjugates were significantly protected from lethal challenge with wild-typeS.Enteritidis (80 to 100% vaccine efficacy).

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