scholarly journals Virulence shift in a sexual clade of Type X Toxoplasma infecting Southern Sea Otters

2021 ◽  
Author(s):  
A Kennard ◽  
MA Miller ◽  
A Khan ◽  
M Quinones ◽  
N Miller ◽  
...  
Keyword(s):  
Intermediate Host ◽  
Host Range ◽  
Chronic Infections ◽  
Epidemic Disease ◽  
Sea Otters ◽  
Highly Pathogenic ◽  
Virulent Strains ◽  
A Genome ◽  
Genetic Cross ◽  
Shift Model

AbstractHow virulent protozoal pathogens capable of causing overt disease are maintained in nature is an important paradigm of eukaryotic pathogenesis. Here we used population genetics and molecular methods to study the evolution and emergence of a marine invasion of new genetic variants of Toxoplasma gondii, referred collectively as Type X (HG12). 53 Toxoplasma isolates were obtained from mustelids that stranded between 1998-2004 with toxoplasmosis (ranging from chronic infection to fatal encephalitis). Over 74% of the sea otters collected throughout their geographic range were infected with Type X as determined by multi-locus PCR-DNA sequencing. Depending on the locus investigated, Type X strains possessed one of three allelic types that had independently assorted across the strains examined; either genetically distinct alleles, referred to as “γ” or “δ”, or a Type II allele. Phylogenetic incongruence among locus-specific trees, genome-wide CGH array and WGS analyses confirmed that Type X is a sexual clade of natural recombinants that resemble F1 progeny from a genetic cross between Type II and a mosaic of two distinct “γ” or “δ” ancestries. A single Type X genotype (19/53; 36%) had expanded in sea otters largely as subclinical chronic infections, but it was highly pathogenic to mice (LD100= 1 parasite). To determine whether murine virulence genes could be mapped within this naturally occurring population, we performed a genome scan and identified four QTLs with LOD scores greater than 4.0. Targeted disruption of ROP33, the strongest candidate from among 16 genes within the highest QTL on Chromosome VIIa established ROP33 as a murine virulence locus. The ability of this highly pathogenic clone to expand and cause the majority of sea otter infections supports a virulence shift model whereby generalist pathogens like Toxoplasma utilize their sexual cycles to produce new strains with an expanded biological potential. Such a trait enables pathogens to extend their host range or be naturally selected within their vast intermediate host range to maximize their transmission. Our work thus establishes a rationale for how virulent strains can be maintained cryptically in nature across a pathogen’s broad host range, and act as reservoirs for epidemic disease.ImportanceWaterborne outbreaks of protozoal parasites are increasingly causing fatal disease in a wide range of animals, including humans. Population expansion of felids near marine estuarine environments has led to increased exposure of marine wildlife to highly infectious Toxoplasma gondii oocysts shed in the feces of cats that are dispersed by storm events. In North America Toxoplasma is thought to possess a highly clonal population structure dominated by 4 clonal lineages (I, II, III, and X). Population genetic analysis of 53 Toxoplasma isolates collected longitudinally from mustelids infected with Toxoplasma that stranded between 1998-2004 identified a majority of otters (74%) to be infected with Type X Toxoplasma, and that Type X is not a clonal lineage, but rather a recombinant clade of strains consistent with a recent genetic cross that produced at least 12 distinct haplotypes. Importantly, one Type X haplotype expanded in 36% of otters across their geographic range and caused relatively benign infections, however it was highly pathogenic to mice. A genome scan was performed to identify a new virulence locus, a secreted serine threonine kinase (ROP33), that is pathogenic in mice, but not sea otters. Our data support a virulence shift model whereby generalist pathogens like Toxoplasma utilize their sexual cycles to produce virulent strains that are maintained cryptically in nature, according to their differential capacity to cause disease within the pathogen’s broad intermediate host range. This type of “zoonotic selection” has important public health implications. Strains capable of causing fatal infections can persist in nature by circulating as chronic infections in intermediate host species that act as reservoirs for epidemic disease.

scholarly journals 1615. Isolation of Lytic Bacteriophages with Broad Host Range Activity Against Pseudomonas aeruginosa Strains Isolated from Respiratory Samples from Cystic Fibrosis Patients Intended for Therapeutic Application

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S801-S801
Author(s):  
Jose Alexander ◽  
Daniel Navas ◽  
Marly Flowers ◽  
Angela Charles ◽  
Amy Carr
Keyword(s):  
Cystic Fibrosis ◽  
Host Range ◽  
Phage Therapy ◽  
Clinical Isolates ◽  
Clinical Samples ◽  
Plaque Morphology ◽  
Broad Host Range ◽  
Chronic Infections ◽  
Clinically Significant ◽  
Host Target

Abstract Background With the rise of the antimicrobial resistance between different genera and species of bacteria, Phage Therapy is becoming a more realistic and accessible option for patients with limited or no antimicrobial options. Being able to have rapid access to a collection of clinical active phages is key for rapid implementation of phage therapy. The Microbiology Department at AdventHealth Orlando is performing routine screening of environmental and patient samples for isolation of phages against non-fermenting Gram negative bacteria to develop a Phage Bank. Methods Protocols for phage isolation from environmental sources such as lakes, rivers and sewers and clinical samples were developed. A series of respiratory, throat, stool and urine samples were processed following an internal protocol that includes centrifugation, filtration and enrichment. Clinical samples were centrifugated for 10 minutes, filtered using 0.45µm centrifugation filters, seeded with targeted host bacteria (clinical isolates) and incubated at 35°C for 24 hours. The enriched samples were centrifugated and filtered for a final phage enriched solution. Screening and isolation were performed using the Gracia method over trypticase soybean agar (TSA) for plaque morphology and quantification. Host range screening of other clinical isolates of P. aeruginosa was performed using the new isolated and purified phages. Results 4 lytic phages against clinical strains of P. aeruginosa from patient with diagnosis of cystic fibrosis (CF), were isolated and purified from 4 different respiratory samples, including sputum and bronchial alveolar lavage. All phages showed phenotypical characteristics of lytic activity. 1 phage was active against 4 strains of P. aeruginosa, 1 phage was active against 2 strains of P. aeruginosa and the remaining 2 phages were active only against the initial host target strain. Conclusion With this study we demonstrated the potential use of clinical samples as source for isolating active bacteriophages against clinically significant bacteria strains. Clinical samples from vulnerable population of patients with chronic infections are part of our routine “phage-hunting” process to stock and grow our Phage Bank project for future clinical use. Disclosures All Authors: No reported disclosures

scholarly journals A Genome Scan Using a Novel Genetic Cross Identifies New Susceptibility Loci and Traits in a Mouse Model of Rheumatoid Arthritis

2000 ◽  
Vol 165 (9) ◽  
pp. 5278-5286 ◽  
Author(s):  
Jeffrey M. Otto ◽  
Raman Chandrasekeran ◽  
Csaba Vermes ◽  
Katalin Mikecz ◽  
Alison Finnegan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Genome Scan ◽  
Susceptibility Loci ◽  
A Genome ◽  
Genetic Cross

scholarly journals Identification of novel sources of resistance to ascochyta blight in a collection of wild Cicer accessions

2020 ◽  
Author(s):  
Toby E. Newman ◽  
Silke Jacques ◽  
Christy Grime ◽  
Fiona L. Kamphuis ◽  
Robert C. Lee ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Ascochyta Blight ◽  
Ascochyta Rabiei ◽  
Sources Of Resistance ◽  
Highly Pathogenic ◽  
Cicer Echinospermum ◽  
Genome Wide ◽  
A Genome ◽  
The Impact ◽  
Chickpea Cultivars

Chickpea production is constrained worldwide by the necrotrophic fungal pathogen Ascochyta rabiei, the causal agent of ascochyta blight (AB). In order to reduce the impact of this disease, novel sources of resistance are required in chickpea cultivars. Here, we screened a new collection of wild Cicer accessions for AB resistance and identified accessions resistant to multiple, highly pathogenic isolates. In addition to this, analyses demonstrated that some collection sites of Cicer echinospermum harbour predominantly resistant accessions, knowledge that can inform future collection missions. Furthermore, a genome-wide association study identified regions of the Cicer reticulatum genome associated with AB resistance and investigation of these regions identified candidate resistance genes. Taken together, these results can be utilised to enhance the resistance of chickpea cultivars to this globally yield-limiting disease.

scholarly journals The NS Segment of an H5N1 Highly Pathogenic Avian Influenza Virus (HPAIV) Is Sufficient To Alter Replication Efficiency, Cell Tropism, and Host Range of an H7N1 HPAIV

2009 ◽  
Vol 84 (4) ◽  
pp. 2122-2133 ◽  
Author(s):  
Wenjun Ma ◽  
Dominique Brenner ◽  
Zhongfang Wang ◽  
Bianca Dauber ◽  
Christina Ehrhardt ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Host Range ◽  
Highly Pathogenic Avian Influenza ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Primary Mouse ◽  
Pathogenic Avian Influenza Virus

ABSTRACT A reassortant avian influenza virus (designated FPV NS GD), carrying the NS-segment of the highly pathogenic avian influenza virus (HPAIV) strain A/Goose/Guangdong/1/96 (GD; H5N1) in the genetic background of the HPAIV strain A/FPV/Rostock/34 (FPV; H7N1), was rescued by reverse genetics. Remarkably, in contrast to the recombinant wild-type FPV (rFPV), the reassortant virus was able to replicate more efficiently in different human cell lines and primary mouse epithelia cells without prior adaptation. Moreover, FPV NS GD caused disease and death in experimentally infected mice and was detected in mouse lungs; in contrast, rFPV was not able to replicate in mice effectively. These results indicated an altered host range and increased virulence. Furthermore FPV NS GD showed pronounced pathogenicity in chicken embryos. In an attempt to define the molecular basis for the apparent differences, we determined that NS1 proteins of the H5N1 and H7N1 strains bound the antiviral kinase PKR and the F2F3 domain of cleavage and polyadenylation specificity factor 30 (CPSF30) with comparable efficiencies in vitro. However, FPV NS GD infection resulted in (i) increased expression of NS1, (ii) faster and stronger PKR inhibition, and (iii) stronger beta interferon promoter inhibition than rFPV. Taken together, the results shed further light on the importance of the NS segment of an H5N1 strain for viral replication, molecular pathogenicity, and host range of HPAIVs and the possible consequences of a reassortment between naturally occurring H7 and H5 type HPAIVs.

Comparison of the early host immune response to two widely diverse virulent strains of Burkholderia pseudomallei that cause acute or chronic infections in BALB/c mice

2015 ◽  
Vol 86 ◽  
pp. 53-63 ◽  
Author(s):  
Kei Amemiya ◽  
Jennifer L. Dankmeyer ◽  
David P. Fetterer ◽  
Patricia L. Worsham ◽  
Susan L. Welkos ◽  
...  
Keyword(s):  
Immune Response ◽  
Burkholderia Pseudomallei ◽  
Host Immune Response ◽  
Chronic Infections ◽  
Virulent Strains

scholarly journals Francisella tularensis Type A Strains Cause the Rapid Encystment of Acanthamoeba castellanii and Survive in Amoebal Cysts for Three Weeks Postinfection

2009 ◽  
Vol 75 (23) ◽  
pp. 7488-7500 ◽  
Author(s):  
Sahar H. El-Etr ◽  
Jeffrey J. Margolis ◽  
Denise Monack ◽  
Richard A. Robison ◽  
Marissa Cohen ◽  
...  
Keyword(s):  
Host Range ◽  
Francisella Tularensis ◽  
Vaccine Strain ◽  
Causative Agent ◽  
Acanthamoeba Castellanii ◽  
Broad Host Range ◽  
Live Vaccine Strain ◽  
Environmental Persistence ◽  
Virulent Strains ◽  
Bioterrorism Agent

ABSTRACT Francisella tularensis, the causative agent of the zoonotic disease tularemia, has recently gained increased attention due to the emergence of tularemia in geographical areas where the disease has been previously unknown and to the organism's potential as a bioterrorism agent. Although F. tularensis has an extremely broad host range, the bacterial reservoir in nature has not been conclusively identified. In this study, the ability of virulent F. tularensis strains to survive and replicate in the amoeba Acanthamoeba castellanii was explored. We observe that A. castellanii trophozoites rapidly encyst in response to F. tularensis infection and that this rapid encystment phenotype is caused by factor(s) secreted by amoebae and/or F. tularensis into the coculture medium. Further, our results indicate that in contrast to the live vaccine strain LVS, virulent strains of F. tularensis can survive in A. castellanii cysts for at least 3 weeks postinfection and that the induction of rapid amoeba encystment is essential for survival. In addition, our data indicate that pathogenic F. tularensis strains block lysosomal fusion in A. castellanii. Taken together, these data suggest that interactions between F. tularensis strains and amoebae may play a role in the environmental persistence of F. tularensis.

Biology and epidemiology ofToxoplasma gondiiin man and animals

2005 ◽  
Vol 6 (1) ◽  
pp. 41-61 ◽  
Author(s):  
Dolores E. Hill ◽  
Sreekumar Chirukandoth ◽  
J. P. Dubey
Keyword(s):  
Toxoplasma Gondii ◽  
Intermediate Host ◽  
Host Range ◽  
Marine Mammals ◽  
Parasitic Infections ◽  
Sea Otter ◽  
Coccidian Parasite ◽  
Wild Carnivores ◽  
Southern Sea Otter

AbstractToxoplasma gondiiis a coccidian parasite which utilizes felids as definitive hosts, and which has an unusually wide intermediate host range. The parasite was initially described by Nicolle and Manceaux in 1908 from the rodent,Ctenodactylus gundi. Infection withT. gondiiis one of the most common parasitic infections of man and other warm-blooded animals. It has been found worldwide from Alaska to Australia. Nearly one-third of humanity has been exposed to this parasite; serologic surveys indicate thatT. gondiiinfections are common in wild carnivores, including pigs, bears, felids, fox, raccoons, and skunks. Clinical and subclinical toxoplasmosis has been reported from wild cervids, ungulates, marsupials, monkeys, and marine mammals. Southern sea otter populations have been severely impacted byToxoplasmainfections.

scholarly journals Cathepsin B Homologue at the Interface between a Parasitic Nematode and Its Intermediate Host

2006 ◽  
Vol 74 (2) ◽  
pp. 1297-1304 ◽  
Author(s):  
Michael S. Duffy ◽  
Deanne K. Cevasco ◽  
Dante S. Zarlenga ◽  
Woraporn Sukhumavasi ◽  
Judith A. Appleton
Keyword(s):  
Intermediate Host ◽  
Cathepsin B ◽  
Parasitic Nematode ◽  
Cysteine Proteases ◽  
Chronic Infections ◽  
Larval Stages ◽  
Snail Intermediate Host ◽  
Putative Active Site ◽  
Domestic Livestock ◽  
Host Tissues

ABSTRACT Parelaphostrongylus tenuis is a parasitic nematode that causes a debilitating neurologic disease in many North American cervids and domestic livestock species. We produced a PCR-based cDNA library from infective larvae (L3) in order to identify molecules that mediate parasitism. A dominant 1,250-bp amplicon encoded a homologue of cathepsin B cysteine proteases. The sequence incorporated a C29G substitution in the putative active site. Antibodies generated against a recombinant form detected the native protein (PtCPR-1) in Western blot assays of L3, but not adult worm, extracts. Immunohistochemical methods revealed that PtCPR-1 synthesis was restricted to larval stages within the snail intermediate host (Triodopsis sp.), beginning as early as 2 days postinfection (dpi) of snails. The protein was present in the intestine and luminal contents and was lost from larvae over time. Concurrent studies showed that larvae induced an immune response in snails beginning at 1 dpi. Layers of hemocytes encapsulated larvae immediately after infection, and granuloma-like structures formed around parasites in chronic infections. Loss of PtCPR-1 from L3 and its accumulation in host tissues coincided with degeneration of granuloma architecture 90 to 105 dpi. Fully developed L3 emerged from the snail at this time. Our data implicate PtCPR-1 in larval development and possibly in the emergence of P. tenuis from the intermediate host. Emerged L3 survived desiccation and cold stress, suggesting that they could remain infectious in the environment. Molecules promoting emergence would facilitate dispersal of L3 and increase the likelihood of transmission to definitive hosts.

scholarly journals Characterization of Low Virulent Strains of Highly Pathogenic A/Hong Kong/156/97 (H5N1) Virus in Mice after Passage in Embryonated Hens' Eggs

Virology ◽  
2000 ◽  
Vol 272 (2) ◽  
pp. 429-437 ◽  
Author(s):  
Yasuaki Hiromoto ◽  
Takehiko Saito ◽  
Stephen Lindstrom ◽  
Kuniaki Nerome
Keyword(s):  
Hong Kong ◽  
H5n1 Virus ◽  
Highly Pathogenic ◽  
Virulent Strains

scholarly journals Identification of Genes Regulating Cell Death inStaphylococcus aureus

2019 ◽  
Author(s):  
Rebecca Yee ◽  
Jie Feng ◽  
Jiou Wang ◽  
Jiazhen Chen ◽  
Ying Zhang
Keyword(s):  
Cell Death ◽  
Acetic Acid ◽  
Drug Targets ◽  
Opportunistic Pathogen ◽  
Infection Model ◽  
Chronic Infections ◽  
Bacterial Cell Death ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms

AbstractStaphylococcus aureusis an opportunistic pathogen that causes acute and chronic infections. Due toS. aureus’ s highly resistant and persistent nature, it is paramount to identify better drug targets in order to eradicateS. aureusinfections. Despite the efforts in understanding bacterial cell death, the genes and pathways ofS. aureuscell death remain elusive. Here, we performed a genome-wide screen using a transposon mutant library to study the genetic mechanisms involved inS. aureuscell death. Using a precisely controlled heat-ramp and acetic acid exposure assays, mutations in 27 core genes (hsdR1, hslO, nsaS, sspA, folD, mfd, vraF, kdpB, USA300HOU_2684, 0868, 0369, 0420, 1154, 0142, 0930, 2590, 0997, 2559, 0044, 2004, 1209, 0152, 2455, 0154, 2386, 0232, 0350 involved in transporters, transcription, metabolism, peptidases, kinases, transferases, SOS response, nucleic acid and protein synthesis) caused the bacteria to be more death-resistant. In addition, we identified mutations in core 10 genes (capA, gltT, mnhG1,USA300HOU_1780, 2496, 0200, 2029, 0336, 0329, 2386, involved in transporters, metabolism, transcription, cell wall synthesis) from heat-ramp and acetic acid that caused the bacteria to be more death-sensitive or with defect in persistence. Interestingly, death-resistant mutants were more virulent than the parental strain USA300 and caused increased mortality in aCaenorhabditis elegansinfection model. Conversely, death-sensitive mutants were less persistent and formed less persister cells upon exposure to different classes of antibiotics. These findings provide new insights into the mechanisms ofS. aureuscell death and offer new therapeutic targets for developing more effective treatments caused byS. aureus.

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