Molecular basis of Corynebacterium diphtheriae virulence and infection in the Caenorhabditis elegans model host

Corynebacterium diphtheriae is the causative agent of cutaneous and pharyngeal diphtheria in humans. While lethality is certainly caused by diphtheria toxin, corynebacterial colonization may primarily require proteinaceous fibers called pili, which mediate adherence to specific tissues. The type strain of C. diphtheriae possesses three distinct pilus structures, namely the SpaA, SpaD, and SpaH-type pili, which are encoded by three distinct pilus gene clusters. The pilus is assembled onto the bacterial peptidoglycan by a specific transpeptidase enzyme called sortase. Although the SpaA pili are shown to be specific for pharyngeal cells in vitro, little is known about functions of the three pili in bacterial pathogenesis. This is mainly due to lack of in vivo models of corynebacterial infection. As an alternative to mouse models as mice do not have functional receptors for diphtheria toxin, in this study I use Caenorhabditis elegans as a model host for C. diphtheriae. A simple C. elegans model would be beneficial in determining the specific role of each pilus-type and the literature suggests that C. elegans infection model can be used to study a variety of bacterial species giving insight into bacterial virulence and host-pathogen interactions. My study examines the hypothesis that pili and toxin are major virulent determinants of C. diphtheriae in the C. elegans model host

Application of a life table approach to assess duration of BNT162b2 vaccine-derived immunity by age using COVID-19 case surveillance data during the Omicron variant period.

BackgroundSARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age.MethodsWeekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination.ResultsThe percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older.ConclusionsThe decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Completed STROBE checklist for observational study and analysis plan information.

Completed STROBE checklist for observational study and analysis plan information.</p

Sensitivity analysis for standardized percent reduction in hazard rate for COVID-19 cases.

Adjusted by an estimate of differential prior infection based on seroprevalence data among the unvaccinated. Shaded area are 95% confidence intervals. A dashed reference line is plotted at a VE of 80%.</p

COVID-19 hazard rates and 95% confidence intervals—22 U.S. jurisdictions, May 1–28, 2022.

Vaccination cohorts 1–4 reached ≥14 days after vaccination with a Pfizer-BioNTech primary series during: January 16–February 5, February 6–26, February 27–April 2, April 3–30, 2022, respectively.</p

Reconfigured schematic of the open vaccination cohorts defining the time origin from the date of vaccination.

The solid lines with arrows indicate subjects in vaccination who subsequently had a positive SARS-Cov-2 test at various points in calendar time. The dotted lines subjects in the vaccination cohort without an observed SARS-Cov-2 test (right-censored). Lines with the same color have the same duration since vaccination to an observed SARS-Cov-2 test. These subjects are pooled to display an analysis with a single common hazard function across the cohorts with time since vaccination as the x-axis. (TIF)</p

Weekly trends in the percent reduction in hazard rate for COVID-19 cases (with 95% confidence intervals) among children 5–17 years vaccinated with a Pfizer-BioNTech primary series as compared to unvaccinated persons by age group and vaccination cohort—22 U.S. jurisdictions, January 16 to May 28, 2022. Vaccination cohorts 1–4 reached ≥14 days after vaccination with a Pfizer-BioNTech primary series during: January 16–February 5, February 6–26, February 27–April 2, April 3–30, 2022, respectively.

Black dashed reference line plotted at a VE of 80%. (TIF)</p