Host adaption to the bacteriophage carrier state of Campylobacter jejuni

The carrier state of the foodborne pathogen Campylobacter jejuni represents an alternative life cycle whereby virulent bacteriophage can persistent in association with host bacteria without commitment to lysogeny. Host bacteria exhibit significant phenotypic changes that improve their ability to survive extra-intestinal environments but exhibit growth phase dependent impairment in motility. We demonstrate that early-exponential phase cultures become synchronised with respect to the non-motile phenotype, which corresponds with a reduction in their ability adhere and invade intestinal epithelial cells. Comparative transcriptome analyses (RNA-seq) identify changes in gene expression that account for the observed phenotypes: down regulation of stress response genes hrcA, hspR and perR; and down regulation of the major flagellin flaA with the chemotactic response signalling genes cheV, cheA and cheW. These changes present mechanisms by which the host and bacteriophage can remain associated without lysis, and the cultures survive extra-intestinal transit. These data provide a basis for understanding a critical link in the ecology of Campylobacter bacteriophage

Performance of Arrhenotokous and Thelytokous Thrips tabaci (Thysanoptera: Thripidae) on Onion and Cabbage and Its Implications on Evolution and Pest Management

Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), is an important pest on onion and cabbage. Two reproductive modes—arrhenotoky and thelytoky—are found in this species and co-occur in the field. We compared life table traits between arrhenotokous and thelytokous T. tabaci on cabbage and onion. Experiments were conducted in cages to determine which reproductive mode is more competitive. Additionally, host adaption of the arrhenotokous and thelytokous T. tabaci between onion and cabbage was investigated. On onion, arrhenotokous T. tabaci performed better than thelytokous T. tabaci, while on cabbage the opposite occurred. When comparing life table and demographic growth parameters (net reproductive rates R0, mean generation time T, the intrinsic rate of natural increase rm, finite rate of increase λ, and population doubling time Td) on different host plants, we found that arrhenotokous T. tabaci performed better on onion than on cabbage, whereas thelytokous T. tabaci performed better on cabbage than on onion. Host-related performance differences in this species suggest that the divergence between two reproductive modes might be associated with host adaption. Pest management strategies for this global pest should recognize that the two reproductive modes can impact population dynamics on different crop

Characterization of mutations in the receptor binding site of influenza A viruses determining virus host, tissue, and cell tropisms using systems biology approaches

Influenza A viruses (IAVs) cause occasional pandemics and seasonal epidemics, thus presenting continuous challenges to public health. Vaccination is the primary strategy for the prevention and control of influenza outbreaks. The antigenicity matched high-yield seed strain is critical for the success of influenza vaccine. Currently, there are several limitations for the influenza vaccine manufacture: 1) the conventional methods for generating such strains are time consuming; 2) egg-based vaccines, the predominant production platform, have several disadvantages including the emergence of viral antigenic variants that can be induced during egg passage; 3) vaccine seed viruses often do not grow efficiently in mammalian cell lines. Previous studies suggested that mutations in the receptor binding site (RBS) that locates at the globular head of the HA1 can change IAVs’ binding specificity, antigenicity, and yield and thus RBS would be an potential target for engineering vaccine seed strain. However, systematic analysis of the mutations on RBS affecting those viral phenotypes is lacking. Specifically, this dissertation has following aims: Firstly, we developed a novel method to rapidly generate high-yield candidate vaccine strains by integrating error-prone PCR, site-directed mutagenesis strategies, and reverse genetics. The error-prone PCR- based reverse genetic system could also be applied to gain-ofunction studies for influenza virus and other pathogens; Secondly, in this dissertation, we identified an Y161F mutation in the hemagglutinin (HA) that enhanced the infectivity and thermostability of virus without changing its original antigenic properties which would prompted the development of cell-based vaccines; Thirdly, the molecular mechanisms underlying host adaption of equine-origin influenza A(H3N8) virus from horses to dogs are unknown. This dissertation identified that a substitution of W222L in the HA of the equine-origin A(H3N8) virus facilitated its host adaption to dogs. This mutation increased binding avidity of the virus specifically to sialyl Lewis X motifs, which were found abundantly in the submucosal glands of dog trachea but not in equine trachea. To summary, this dissertation investigated the role of RBS in IAVs biology and expanded the current knowledge toward IAV vaccine strain engineering, IAV host adaption and evolution

Cryptosporidium

The protozoan Cryptosporidium is notorious for its resistance to chlorine disinfection, a mainstay of water treatment. Human infections, mainly of the small intestine, arise from consumption of faecally contaminated food or water, environmental exposure, and person-to-person or animal-to-person spread. Acute gastrointestinal symptoms can be prolonged but are usually self-limiting. Problems arise with immune-deficient, including malnourished, people including chronic diarrhoea, hepato-biliary tree and extra-gastrointestinal site infection, and few options for treatment or prevention exist. Although genomics has enabled refined classification, identification of chemotherapeutic targets and vaccine candidates, and putative factors for host adaption and pathogenesis, their confirmation has been hampered by a lack of biological tools

Epidemiological characteristics of coronavirus disease 2019 (COVID-19) patients in IRAN: A single center study.

BackgroundAn outbreak of COVID-19 in Iran has spread throughout the country. Identifying the epidemiological characteristics of this disease will help to make appropriate decisions and thus control the epidemic. The aim of this study was characterization of the epidemiological features of COVID-19 in Iran.MethodsIn this retrospective study, data related to the epidemiological characteristics of COVID-19 patients admitted to Baqiyatallah Hospital in Tehran, Iran, from 19 February 2020 to 15 April 2020 have been analyzed and reported. Patient characteristics including age, gender and underlying diseases were investigated. Data were collected through patient records. Sex ratio, Case Fatality Rate (CFR) and daily trend of cases were also determined. A multiple logistic regression analysis was also performed to assess affecting factors on mortality.ResultsFrom February 19, 2020 to April 15, 2020, 12870 patients referred to the hospital emergency department, of which 2968 were hospitalized with COVID-19 diagnosis. The majority of cases were in the age group of 50 to 60 years of old. The male-to-female ratio was 1.93:1. A total of 239 deaths occurred among all cases for an overall CFR of 1.85% based on the total number of patients (both outpatient and inpatient) and 8.06% among hospitalized patients. Out of all patients 10.89% had comorbidity. Diabetes, chronic respiratory diseases, hypertension, cardiovascular diseases, chronic Kidney diseases and cancer were the most common comorbidities with 3.81, 2.02 , 1.99 , 1.25, 0.60 and 0.57 %, respectively. Male gender (OR=1.45, 95% CI: 1.08-1.96), older age (OR=1.05, 95% CI: 1.04-1.06) and having underlying diseases (OR=1.53, 95% CI: 1.04-2.24) were significantly associated with mortality.ConclusionsThe results of this study showed that Male gender, older age and having comorbidities were significantly associated with the risk of death among COVID-19 patients. It is important to pay special attention to male elderly patients with underlying diseases

Genomic Analysis of Companion Rabbit Staphylococcus aureus.

In addition to being an important human pathogen, Staphylococcus aureus is able to cause a variety of infections in numerous other host species. While the S. aureus strains causing infection in several of these hosts have been well characterised, this is not the case for companion rabbits (Oryctolagus cuniculus), where little data are available on S. aureus strains from this host. To address this deficiency we have performed antimicrobial susceptibility testing and genome sequencing on a collection of S. aureus isolates from companion rabbits. The findings show a diverse S. aureus population is able to cause infection in this host, and while antimicrobial resistance was uncommon, the isolates possess a range of known and putative virulence factors consistent with a diverse clinical presentation in companion rabbits including severe abscesses. We additionally show that companion rabbit isolates carry polymorphisms within dltB as described as underlying host-adaption of S. aureus to farmed rabbits. The availability of S. aureus genome sequences from companion rabbits provides an important aid to understanding the pathogenesis of disease in this host and in the clinical management and surveillance of these infections.This project was supported by internal funding from the School of Biological, Biomedical and Environmental Sciences, University of Hull (GKP), a Medical Research Council (MRC) Partnership Grant (G1001787/1) (MAH and JP), and the Wellcome Trust, Grant number 098051 (JP).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.015145

A Tractable Experimental Model for Study of Human and Animal Scabies

Scabies, a neglected parasitic disease caused by the microscopic mite Sarcoptes scabiei, is a major driving force behind bacterial skin infections in tropical settings. Aboriginal and Torres Strait Islander peoples are nearly twenty times more likely to die from acute rheumatic fever and rheumatic heart disease than individuals from the wider Australian community. These conditions are caused by bacterial pathogens such as Group A streptococci, which have been linked to underlying scabies infestations. Community based initiatives to reduce scabies and associated disease have expanded, but have been threatened in recent years by emerging drug resistance. Critical biological questions surrounding scabies remain unanswered due to a lack of biomedical research. This has been due in part to a lack of either a suitable animal model or an in vitro culture system for scabies mites. The pig/mite model reported here will be a much needed resource for parasite material and will facilitate in vivo studies on host immune responses to scabies, including relations to associated bacterial pathogenesis, and more detailed studies of molecular evolution and host adaptation. It represents the missing tool to extrapolate emerging molecular data into an in vivo setting and may well allow the development of clinical interventions