Faculty Opinions recommendation of Host-pathogen o-methyltransferase similarity and its specific presence in highly virulent strains of Francisella tularensis suggests molecular mimicry.

2011 ◽  
Author(s):  
George Petrikkos ◽  
Sotirios Tsiodras
Keyword(s):  
Francisella Tularensis ◽  
Molecular Mimicry ◽  
Virulent Strains ◽  
Host Pathogen ◽  
Highly Virulent

Peripheral human γδ T cells control growth of both avirulent and highly virulent strains of Francisella tularensis in vitro

2012 ◽  
Vol 14 (7-8) ◽  
pp. 584-589 ◽  
Author(s):  
Caroline A. Rowland ◽  
M. Gill Hartley ◽  
Helen Flick-Smith ◽  
Thomas R. Laws ◽  
Jim E. Eyles ◽  
...  
Keyword(s):  
T Cells ◽  
Francisella Tularensis ◽  
Γδ T Cells ◽  
Virulent Strains ◽  
Control Growth ◽  
Highly Virulent

How Molecular Epidemiology Can Affect Tuberculosis Control in the Middle East Countries: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Asgharzadeh ◽  
Jalil Rashedi ◽  
Behroz Mahdavi Poor ◽  
Hossein Samadi kafil ◽  
Hossein Moharram Zadeh ◽  
...  
Keyword(s):  
Middle East ◽  
Molecular Epidemiology ◽  
Average Rate ◽  
Meta Analysis ◽  
Close Monitoring ◽  
Drug Resistant ◽  
Middle East Countries ◽  
Virulent Strains ◽  
Recent Transmission ◽  
Highly Virulent

: Nowadays, due to the incidence of specific strains of Mycobacterium tuberculosis and also increase the rate of drug resistant-TB mortality rate has elevated by this disease. Identification of common strains in the region as well as sources of transmission are essential to control the disease that this has been possible by using molecular epidemiology. In this survey, studies which have been carried out based on spoligotyping method in Muslim Middle East countries were considered to determine their role in control of TB. All studies conducted from 2005 to June 2016 were considered systematically in three electronic data bases and finally, 23 studies were selected. The average rate of clustering was 84% and the rate of recent transmission was variable from 21.7% to 92.4%. Incidence of Beijing strains was been rising in the considered countries. In Iran and Saudi Arabia which are immigration and labour-hosting countries, respectively, rapid transmittable strains and drug resistant Beijings were higher than other considered countries. Considering the incidence of highly virulent strains, due to the increase of immigration and people infected with HIV, tuberculosis, especially drug resistant form, the lack of close monitoring in the future will be induce trouble.

scholarly journals Sero- and apx-typing of German Actinobacillus pleuropneumoniae field isolates from 2010 to 2019 reveals a predominance of serovar 2 with regular apx-profile

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Lukas Schuwerk ◽  
Doris Hoeltig ◽  
Karl-Heinz Waldmann ◽  
Peter Valentin-Weigand ◽  
Judith Rohde
Keyword(s):  
Reference Strain ◽  
Actinobacillus Pleuropneumoniae ◽  
Etiological Agent ◽  
Toxin Gene ◽  
Gene Profile ◽  
Field Isolates ◽  
Porcine Pleuropneumonia ◽  
Virulent Strains ◽  
Highly Virulent

AbstractSerotyping is the most common method to characterize field isolates of Actinobacillus (A.) pleuropneumoniae, the etiological agent of porcine pleuropneumonia. Based on serology, many farms seem to be infected and antibodies against a wide variety of serovars are detectable, but, so far it is unknown to what degree respective serovars contribute to outbreaks of clinical manifest disease. In this study, 213 German A. pleuropneumoniae field isolates retrieved for diagnostic purposes from outbreaks of porcine pleuropneumonia between 2010 and 2019 were genetically serotyped and analyzed regarding their apx-toxin gene profile using molecular methods. Serotyping revealed a prominent role of serovar 2 in clinical cases (64% of all isolates) and an increase in the detection of this serovar since 2010 in German isolates. Serovar 9/11 followed as the second most frequent serovar with about 15% of the isolates. Furthermore, very recently described serovars 16 (n = 2) and 18 (n = 8) were detected. Most isolates (93.4%) showed apx-profiles typical for the respective serovar. However, this does not hold true for isolates of serovar 18, as 75% (n = 6) of all isolates of this serovar deviated uniformly from the “typical” apx-gene profile of the reference strain 7311555. Notably, isolates from systemic lesions such as joints or meninges did not harbor the complete apxICABD operon which is considered typical for highly virulent strains. Furthermore, the extremely low occurrence (n = 1) of NAD independent (biovar II) isolates in German A. pleuropneumoniae was evident in our collection of clinical isolates.

scholarly journals Label-Free Quantitative Acetylome Analysis Reveals Toxoplasma gondii Genotype-Specific Acetylomic Signatures

2019 ◽  
Vol 7 (11) ◽  
pp. 510 ◽  
Author(s):  
Ze-Xiang Wang ◽  
Rui-Si Hu ◽  
Chun-Xue Zhou ◽  
Jun-Jun He ◽  
Hany M. Elsheikha ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Label Free ◽  
Histone Acetyl Transferase ◽  
Genotype I ◽  
Host Cell Response ◽  
Genotype Iii ◽  
Virulent Strains ◽  
Highly Virulent ◽  
Insight Into ◽  
Specific Virulence

Distinct genotypic and pathogenic differences exist between Toxoplasma gondii genotypes. For example, genotype I is highly virulent, whereas genotype II and genotype III are less virulent. Moreover, Chinese 1 genotype (ToxoDB#9) is also virulent. Here, we compare the acetylomes of genotype 1 (RH strain) and Chinese 1 genotype (ToxoDB#9, PYS strain) of T. gondii. Using mass spectrometry enriched for acetylated peptides, we found a relationship between the levels of protein acetylation and parasite genotype-specific virulence. Notably, lysine acetylation was the largest (458 acetylated proteins) in RH strain, followed by PYS strain (188 acetylated proteins), whereas only 115 acetylated proteins were detected in PRU strain. Our analysis revealed four, three, and four motifs in RH strain, PRU strain and PYS strain, respectively. Three conserved sequences around acetylation sites, namely, xxxxxKAcHxxxx, xxxxxKAcFxxxx, and xxxxGKAcSxxxx, were detected in the acetylome of the three strains. However, xxxxxKAcNxxxx (asparagine) was found in RH and PYS strains but was absent in PRU strain. Our analysis also identified 15, 3, and 26 differentially expressed acetylated proteins in RH strain vs. PRU strain, PRU strain vs. PYS strain and PYS strain vs. RH strain, respectively. KEGG pathway analysis showed that a large proportion of the acetylated proteins are involved in metabolic processes. Pathways for the biosynthesis of secondary metabolites, biosynthesis of antibiotics and microbial metabolism in diverse environments were featured in the top five enriched pathways in all three strains. However, acetylated proteins from the virulent strains (RH and PYS) were more enriched in the pyruvate metabolism pathway compared to acetylated proteins from PRU strain. Increased levels of histone-acetyl-transferase and glycyl-tRNA synthase were detected in RH strain compared to PRU strain and PYS strain. Both enzymes play roles in stress tolerance and proliferation, key features in the parasite virulence. These findings reveal novel insight into the acetylomic profiles of major T. gondii genotypes and provide a new important resource for further investigations of the roles of the acetylated parasite proteins in the modulation of the host cell response to the infection of T. gondii.

scholarly journals OpiA, a Type Six Secretion System Substrate, Localizes to the Cell Pole and Plays a Role in Bacterial Growth and Viability in Francisella tularensis LVS

2020 ◽  
Vol 202 (14) ◽  
Author(s):  
Stuart Cantlay ◽  
Kristen Haggerty ◽  
Joseph Horzempa
Keyword(s):  
Cell Size ◽  
Francisella Tularensis ◽  
Secretion System ◽  
Live Vaccine ◽  
Intracellular Pathogen ◽  
Content Type ◽  
Erythrocyte Invasion ◽  
Host Pathogen

ABSTRACT Francisella tularensis is an intracellular pathogen and the causative agent of tularemia. The F. tularensis type six secretion system (T6SS) is required for a number of host-pathogen interactions, including phagolysosomal escape and invasion of erythrocytes. One known effector of the T6SS, OpiA, has recently been shown to be a phosphatidylinositol-3 kinase. To investigate the role of OpiA in erythrocyte invasion, we constructed an opiA-null mutant in the live vaccine strain, F. tularensis LVS. OpiA was not required for erythrocyte invasion; however, deletion of opiA affected growth of F. tularensis LVS in broth cultures in a medium-dependent manner. We also found that opiA influenced cell size, gentamicin sensitivity, bacterial viability, and the lipid content of F. tularensis. A fluorescently tagged OpiA (OpiA–emerald-green fluorescent protein [EmGFP]) accumulated at the cell poles of F. tularensis, which is consistent with the location of the T6SS. However, OpiA-EmGFP also exhibited a highly dynamic localization, and this fusion protein was detected in erythrocytes and THP-1 cells in vitro, further supporting that OpiA is secreted. Similar to previous reports with F. novicida, our data demonstrated that opiA had a minimal effect on intracellular replication of F. tularensis in host immune cells in vitro. However, THP-1 cells infected with the opiA mutant produced modestly (but significantly) higher levels of the proinflammatory cytokine tumor necrosis factor alpha compared to these host cells infected with wild-type bacteria. We conclude that, in addition to its role in host-pathogen interactions, our results reveal that the function of opiA is central to the biology of F. tularensis bacteria. IMPORTANCE F. tularensis is a pathogenic intracellular pathogen that is of importance for public health and strategic defense. This study characterizes the opiA gene of F. tularensis LVS, an attenuated strain that has been used as a live vaccine but that also shares significant genetic similarity to related Francisella strains that cause human disease. The data presented here provide the first evidence of a T6SS effector protein that affects the physiology of F. tularensis, namely, the growth, cell size, viability, and aminoglycoside resistance of F. tularensis LVS. This study also adds insight into our understanding of OpiA as a determinant of virulence. Finally, the fluorescence fusion constructs presented here will be useful tools for dissecting the role of OpiA in infection.

scholarly journals Inhibitors of Ribosome Rescue Arrest Growth of Francisella tularensis at All Stages of Intracellular Replication

2016 ◽  
Vol 60 (6) ◽  
pp. 3276-3282 ◽  
Author(s):  
Tyler D. P. Goralski ◽  
Kalyan K. Dewan ◽  
John N. Alumasa ◽  
Victoria Avanzato ◽  
David E. Place ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Francisella Tularensis ◽  
Ex Vivo ◽  
Eukaryotic Cells ◽  
Content Type ◽  
Antibiotic Development ◽  
Bacterial Proliferation ◽  
Virulent Strains ◽  
Arrest Growth

Bacteria require at least one pathway to rescue ribosomes stalled at the ends of mRNAs. The primary pathway for ribosome rescue istrans-translation, which is conserved in >99% of sequenced bacterial genomes. Some species also have backup systems, such as ArfA or ArfB, which can rescue ribosomes in the absence of sufficienttrans-translation activity. Small-molecule inhibitors of ribosome rescue have broad-spectrum antimicrobial activity against bacteria grown in liquid culture. These compounds were tested against the tier 1 select agentFrancisella tularensisto determine if they can limit bacterial proliferation during infection of eukaryotic cells. The inhibitors KKL-10 and KKL-40 exhibited exceptional antimicrobial activity against both attenuated and fully virulent strains ofF. tularensisin vitroand duringex vivoinfection. Addition of KKL-10 or KKL-40 to macrophages or liver cells at any time after infection byF. tularensisprevented further bacterial proliferation. When macrophages were stimulated with the proinflammatory cytokine gamma interferon before being infected byF. tularensis, addition of KKL-10 or KKL-40 reduced intracellular bacteria by >99%, indicating that the combination of cytokine-induced stress and a nonfunctional ribosome rescue pathway is fatal toF. tularensis. Neither KKL-10 nor KKL-40 was cytotoxic to eukaryotic cells in culture. These results demonstrate that ribosome rescue is required forF. tularensisgrowth at all stages of its infection cycle and suggest that KKL-10 and KKL-40 are good lead compounds for antibiotic development.

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