scholarly journals Large-Scale Screen Highlights the Importance of Capsule for Virulence in the Zoonotic Pathogen Streptococcus iniae

2005 ◽  
Vol 73 (2) ◽  
pp. 921-934 ◽  
Author(s):  
Jesse D. Miller ◽  
Melody N. Neely
Keyword(s):  
Large Scale ◽  
Disease Model ◽  
Systemic Infection ◽  
Streptococcus Iniae ◽  
Species Barrier ◽  
Zebrafish Model ◽  
Zoonotic Pathogen ◽  
Infectious Disease Model ◽  
Successful Infection ◽  
Human Specific

ABSTRACT Zoonotic pathogens have the unique ability to cross the species barrier, causing disease in both humans and specific animal hosts. Streptococcus iniae is a zoonotic pathogen of both fish and humans, and the clinical presentations of S. iniae infections in fish and humans are very similar to those caused by various human-specific streptococcal pathogens. Virulence mechanisms required for infection by this pathogen of either host have yet to be determined. Using the previously reported zebrafish infectious disease model, we performed a large-scale screening to determine genes required for systemic infection. Screening 1,128 signature-tagged transposon mutants through the zebrafish model allowed identification of 41 potential mutants that were unable to survive within the host environment. Greater than 50% of the mutants that could be identified through homology searches were highly homologous to genes found in other human-specific streptococcal pathogens, while 32% were found to have no homology to any sequences found in the databases, suggesting as yet unknown gram-positive bacterial virulence factors. A large percentage of the insertions were found to be located in several putative capsule synthesis genes, an important virulence component for other systemic pathogens. Density gradient assays demonstrated that several of these putative capsule mutants have dissimilar buoyant densities, suggesting different levels of capsule synthesis. Putative capsule mutants were also less resistant to phagocytosis in whole-blood assays than wild-type S. iniae. Our initial large-scale characterization of S. iniae virulence highlights the importance of the capsule for successful infection.

scholarly journals Innate Immune Response to Streptococcus iniae Infection in Zebrafish Larvae

2012 ◽  
Vol 81 (1) ◽  
pp. 110-121 ◽  
Author(s):  
Elizabeth A. Harvie ◽  
Julie M. Green ◽  
Melody N. Neely ◽  
Anna Huttenlocher
Keyword(s):  
Systemic Infection ◽  
Neutrophil Function ◽  
Otic Vesicle ◽  
Streptococcus Iniae ◽  
Wild Type ◽  
Zebrafish Model ◽  
Content Type ◽  
Larval Zebrafish ◽  
Zebrafish Larvae ◽  
Lethal Infection

Streptococcus iniaecauses systemic infection characterized by meningitis and sepsis. Here, we report a larval zebrafish model ofS. iniaeinfection. Injection of wild-typeS. iniaeinto the otic vesicle induced a lethal infection by 24 h postinfection. In contrast, anS. iniaemutant deficient in polysaccharide capsule (cpsAmutant) was not lethal, with greater than 90% survival at 24 h postinfection. Live imaging demonstrated that both neutrophils and macrophages were recruited to localized otic infection with mutant and wild-typeS. iniaeand were able to phagocytose bacteria. Depletion of neutrophils and macrophages impaired host survival following infection with wild-typeS. iniaeand thecpsAmutant, suggesting that leukocytes are critical for host survival in the presence of both the wild-type and mutant bacteria. However, zebrafish larvae with impaired neutrophil function but normal macrophage function had increased susceptibility to wild-type bacteria but not thecpsAmutant. Taking these findings together, we have developed a larval zebrafish model ofS. iniaeinfection and have found that although neutrophils are important for controlling infection with wild-typeS. iniae, neutrophils are not necessary for host defense against thecpsAmutant.

scholarly journals First Streptococcus pyogenes Signature-Tagged Mutagenesis Screen Identifies Novel Virulence Determinants

2009 ◽  
Vol 77 (5) ◽  
pp. 1854-1865 ◽  
Author(s):  
Anne E. Kizy ◽  
Melody N. Neely
Keyword(s):  
Streptococcus Pyogenes ◽  
Large Scale ◽  
Virulence Genes ◽  
Insertion Site ◽  
Disease Model ◽  
Invasive Infection ◽  
Virulence Determinants ◽  
Infectious Disease Model

ABSTRACT The virulence of bacterial pathogens is a complex process that requires the dynamic expression of many genes for the pathogens to invade and circumvent host defenses, as well as to proliferate in vivo. In this study, we employed a large-scale screen, signature-tagged mutagenesis (STM), to identify Streptococcus pyogenes virulence genes important for pathogenesis within the host. Approximately 1,200 STM mutants were created and screened using the zebrafish infectious disease model. The transposon insertion site was identified for 29 of the 150 mutants that were considered attenuated for virulence. Previously reported streptococcal virulence genes, such as mga, hasA, amrA, smeZ, and two genes in the sil locus, were identified, confirming the utility of the model for revealing genes important for virulence. Multiple genes not previously implicated in virulence were also identified, including genes encoding putative transporters, hypothetical cytosolic proteins, and macrolide efflux pumps. The STM mutant strains display various levels of attenuation, and multiple separate insertions were identified in either the same gene or the same locus, suggesting that these factors are important for this type of acute, invasive infection. We further examined two such genes, silB and silC of a putative quorum-sensing regulon, and determined that they are significant virulence factors in our model of necrotizing fasciitis. sil locus promoter expression was examined under various in vitro conditions, as well as in zebrafish tissues, and was found to be differentially induced. This study was a unique investigation of S. pyogenes factors required for successful invasive infection.

Power comparison of Cochran-Armitage trend test against allelic and genotypic tests in large-scale case-control genetic association studies

2016 ◽  
Vol 27 (9) ◽  
pp. 2657-2673 ◽  
Author(s):  
Mathieu Emily
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Disease Model ◽  
Trend Test ◽  
Genome Wide Association Studies ◽  
Power Functions ◽  
Power Comparison ◽  
Powerful Test ◽  
Armitage Trend Test ◽  
Mode Of Inheritance

The Cochran-Armitage trend test (CA) has become a standard procedure for association testing in large-scale genome-wide association studies (GWAS). However, when the disease model is unknown, there is no consensus on the most powerful test to be used between CA, allelic, and genotypic tests. In this article, we tackle the question of whether CA is best suited to single-locus scanning in GWAS and propose a power comparison of CA against allelic and genotypic tests. Our approach relies on the evaluation of the Taylor decompositions of non-centrality parameters, thus allowing an analytical comparison of the power functions of the tests. Compared to simulation-based comparison, our approach offers the advantage of simultaneously accounting for the multidimensionality of the set of features involved in power functions. Although power for CA depends on the sample size, the case-to-control ratio and the minor allelic frequency (MAF), our results first show that it is largely influenced by the mode of inheritance and a deviation from Hardy–Weinberg Equilibrium (HWE). Furthermore, when compared to other tests, CA is shown to be the most powerful test under a multiplicative disease model or when the single-nucleotide polymorphism largely deviates from HWE. In all other situations, CA lacks in power and differences can be substantial, especially for the recessive mode of inheritance. Finally, our results are illustrated by the comparison of the performances of the statistics in two genome scans.

scholarly journals Fatal Streptococcus iniae Infection in a Juvenile Free-Ranging Short-Beaked Common Dolphin (Delphinus delphis)

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3123
Author(s):  
Rebecca Souter ◽  
Anne-Lise Chaber ◽  
Ken Lee ◽  
Aaron Machado ◽  
Jia Lam ◽  
...  
Keyword(s):  
Marine Mammals ◽  
Skin Lesions ◽  
Streptococcus Iniae ◽  
Common Dolphin ◽  
Farmed Fish ◽  
Fish Stocks ◽  
Zoonotic Pathogen ◽  
Delphinus Delphis ◽  
Source Of Infection ◽  
Free Ranging

Streptococcus iniae (S. iniae) is a significant aquatic pathogen of farmed fish species, important zoonotic pathogen, and reported cause of disease in captive Amazon River dolphins (Inia geoffrensis) and a bottlenose dolphin (Tursiops truncatus). Here we report S. iniae as the cause of subcutaneous abscesses, sepsis and mortality in a juvenile free-ranging short-beaked common dolphin (Delphinus delphis) found deceased on a metropolitan Australian beach. Body surfaces were covered by multifocal, depressed, deep, irregular cutaneous ulcerations, which microscopically were characterised by ruptured subcutaneous abscesses with intralesional cocci. Routine microbiological investigations revealed a heavy growth of beta-haemolytic Streptococcus sp. identified as Streptococcus iniae in skin lesions as well as from heart blood, the latter supportive of sepsis. Tissues were negative for cetacean morbillivirus and no other disease processes were identified. S. iniae has not been reported in free-ranging marine mammals, nor in Australian delphinids, previously. More notably a pathogen of captive animals, this case report identifies S. iniae as a pathogen of wild dolphins also. In addition to expanding the host reservoir of a significant zoonotic pathogen, determining the source of infection as well as possible consequences for other marine mammals and wild and intensive fish stocks warrants further investigations.

scholarly journals Obesity as an "infectious" disease

2021 ◽  
Vol 11 (9) ◽  
pp. 534-537
Author(s):  
Daria Żuraw ◽  
Paulina Oleksa ◽  
Mateusz Sobczyk
Keyword(s):  
Infectious Disease ◽  
Disease Model ◽  
Living Environment ◽  
Social Contagion ◽  
Social Discrimination ◽  
Obese People ◽  
Obesity Epidemic ◽  
Global Epidemic ◽  
Infectious Disease Model ◽  
The One

Introduction: Obesity has been recognized as a global epidemic by the WHO, followed by a wealth of empirical evidence supporting its contagiousness. However, the dynamics of the spread of obesity between individuals are rarely studied.  A distinguishing feature of the obesity epidemic is that it is driven by a process of social contagion that cannot be perfectly described by the infectious disease model. There is also social discrimination in the obesity epidemic. Social discrimination against obese people plays quite different roles in two cases: on the one hand, when obesity cannot be eliminated, social discrimination can reduce the number of obese people; on the other hand, when obesity is eradicable, social discrimination can cause it to explode.(1)   Materiał and methods: A literature analysis on obesity epidemic was carried out within the Pubmed, Google scholar and Research Gate platform. The following keywords were used in serach: obesity, epidemy, children, body max index.    Purpose of the work: The aim of the following analysis is to present an obesity as an infectious disease. The steadily increasing percentage of obese people, including children, shows that there is an obesity epidemic. This is the phenomenon of social contagion, which partially explains the concept of homophily, which involves the grouping of people with similar characteristics. Potential explanations are also provided by sharing a living environment with similar access to certain foods and similar opportunities for physical activity, which defines the occurrence of analogous health habits

Improving Computational Models and Practices

2012 ◽  
pp. 432-455
Author(s):  
Iain Barrass ◽  
Joanna Leng
Keyword(s):  
Public Health ◽  
Infectious Disease ◽  
Computational Models ◽  
Disease Model ◽  
Significant Risk ◽  
Epidemiological Studies ◽  
Health Interventions ◽  
Computational Steering ◽  
Infectious Disease Model

Since infectious diseases pose a significant risk to human health many countries aim to control their spread. Public health bodies faced with a disease threat must understand the disease’s progression and its transmission process. From this understanding it is possible to evaluate public health interventions intended to decrease impacts on the population. Commonly, contingency planning has been achieved through epidemiological studies and the use of relatively simple models. However, computational methods increasingly allow more complex, and potentially more realistic, simulations of various scenarios of the control of the spread of disease. However, understanding computational results from more sophisticated models can pose considerable challenges. A case study of a system combining a complex infectious disease model with interactive visualization and computational steering tools shows some of the opportunities this approach offers to infectious disease control.

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