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1. Advances in Foodborne Pathogen Analysis

   https://doi.org/10.3390/foods9111635  

   Bhunia, Arun K. ; Bisha, Bledar ; Gehring, Andrew G. ; Brehm-Stecher, Byron F. ( November 2020 , Foods)

   As the world population has grown, new demands on the production of foods have been met by increased efficiencies in production, from planting and harvesting to processing, packaging and distribution to retail locations. These efficiencies enable rapid intranational and global dissemination of foods, providing longer “face time” for products on retail shelves and allowing consumers to make healthy dietary choices year-round. However, our food production capabilities have outpaced the capacity of traditional detection methods to ensure our foods are safe. Traditional methods for culture-based detection and characterization of microorganisms are time-, labor- and, in some instances, space- and infrastructure-intensive, and are therefore not compatible with current (or future) production and processing realities. New and versatile detection methods requiring fewer overall resources (time, labor, space, equipment, cost, etc.) are needed to transform the throughput and safety dimensions of the food industry. Access to new, user-friendly, and point-of-care testing technologies may help expand the use and ease of testing, allowing stakeholders to leverage the data obtained to reduce their operating risk and health risks to the public. The papers in this Special Issue on “Advances in Foodborne Pathogen Analysis” address critical issues in rapid pathogen analysis, including preanalytical sample preparation, portable andmore »field-capable test methods, the prevalence of antibiotic resistance in zoonotic pathogens and non-bacterial pathogens, such as viruses and protozoa.« less
2. Contribution of Pseudomonas aeruginosa Exopolysaccharides Pel and Psl to Wound Infections

   https://doi.org/10.3389/fcimb.2022.835754  

   Fleming, Derek ; Niese, Brandon ; Redman, Whitni ; Vanderpool, Emily ; Gordon, Vernita ; Rumbaugh, Kendra P. ( April 2022 , Frontiers in Cellular and Infection Microbiology)

   Biofilms are the cause of most chronic bacterial infections. Living within the biofilm matrix, which is made of extracellular substances, including polysaccharides, proteins, eDNA, lipids and other molecules, provides microorganisms protection from antimicrobials and the host immune response. Exopolysaccharides are major structural components of bacterial biofilms and are thought to be vital to numerous aspects of biofilm formation and persistence, including adherence to surfaces, coherence with other biofilm-associated cells, mechanical stability, protection against desiccation, binding of enzymes, and nutrient acquisition and storage, as well as protection against antimicrobials, host immune cells and molecules, and environmental stressors. However, the contribution of specific exopolysaccharide types to the pathogenesis of biofilm infection is not well understood. In this study we examined whether the absence of the two main exopolysaccharides produced by the biofilm former Pseudomonas aeruginosa would affect wound infection in a mouse model. Using P. aeruginosa mutants that do not produce the exopolysaccharides Pel and/or Psl we observed that the severity of wound infections was not grossly affected; both the bacterial load in the wounds and the wound closure rates were unchanged. However, the size and spatial distribution of biofilm aggregates in the wound tissue were significantly different when Pel and Pslmore »were not produced, and the ability of the mutants to survive antibiotic treatment was also impaired. Taken together, our data suggest that while the production of Pel and Psl do not appear to affect P. aeruginosa pathogenesis in mouse wound infections, they may have an important implication for bacterial persistence in vivo.« less
3. Resistance-Guided Mining of Bacterial Genotoxins Defines a Family of DNA Glycosylases

   https://doi.org/10.1128/mbio.03297-21  

   Bradley, Noah P. ; Wahl, Katherine L. ; Steenwyk, Jacob L. ; Rokas, Antonis ; Eichman, Brandt F. ( April 2022 , mBio)

   Simmons, Lyle A. ; Bush, Karen (Ed.)

   ABSTRACT Unique DNA repair enzymes that provide self-resistance against therapeutically important, genotoxic natural products have been discovered in bacterial biosynthetic gene clusters (BGCs). Among these, the DNA glycosylase AlkZ is essential for azinomycin B production and belongs to the HTH_42 superfamily of uncharacterized proteins. Despite their widespread existence in antibiotic producers and pathogens, the roles of these proteins in production of other natural products are unknown. Here, we determine the evolutionary relationship and genomic distribution of all HTH_42 proteins from Streptomyces and use a resistance-based genome mining approach to identify homologs associated with known and uncharacterized BGCs. We find that AlkZ-like (AZL) proteins constitute one distinct HTH_42 subfamily and are highly enriched in BGCs and variable in sequence, suggesting each has evolved to protect against a specific secondary metabolite. As a validation of the approach, we show that the AZL protein, HedH4, associated with biosynthesis of the alkylating agent hedamycin, excises hedamycin-DNA adducts with exquisite specificity and provides resistance to the natural product in cells. We also identify a second, phylogenetically and functionally distinct subfamily whose proteins are never associated with BGCs, are highly conserved with respect to sequence and genomic neighborhood, and repair DNA lesions not associated with amore »particular natural product. This work delineates two related families of DNA repair enzymes—one specific for complex alkyl-DNA lesions and involved in self-resistance to antimicrobials and the other likely involved in protection against an array of genotoxins—and provides a framework for targeted discovery of new genotoxic compounds with therapeutic potential. IMPORTANCE Bacteria are rich sources of secondary metabolites that include DNA-damaging genotoxins with antitumor/antibiotic properties. Although Streptomyces produce a diverse number of therapeutic genotoxins, efforts toward targeted discovery of biosynthetic gene clusters (BGCs) producing DNA-damaging agents is lacking. Moreover, work on toxin-resistance genes has lagged behind our understanding of those involved in natural product synthesis. Here, we identified over 70 uncharacterized BGCs producing potentially novel genotoxins through resistance-based genome mining using the azinomycin B-resistance DNA glycosylase AlkZ. We validate our analysis by characterizing the enzymatic activity and cellular resistance of one AlkZ ortholog in the BGC of hedamycin, a potent DNA alkylating agent. Moreover, we uncover a second, phylogenetically distinct family of proteins related to Escherichia coli YcaQ, a DNA glycosylase capable of unhooking interstrand DNA cross-links, which differs from the AlkZ-like family in sequence, genomic location, proximity to BGCs, and substrate specificity. This work defines two families of DNA glycosylase for specialized repair of complex genotoxic natural products and generalized repair of a broad range of alkyl-DNA adducts and provides a framework for targeted discovery of new compounds with therapeutic potential.« less
4. Integrating plant molecular farming and materials research for next-generation vaccines

   https://doi.org/10.1038/s41578-021-00399-5  

   Chung, Young Hun ; Church, Derek ; Koellhoffer, Edward C. ; Osota, Elizabeth ; Shukla, Sourabh ; Rybicki, Edward P. ; Pokorski, Jonathan K. ; Steinmetz, Nicole F. ( December 2021 , Nature Reviews Materials)

   Biologics — medications derived from a biological source — are increasingly used as pharmaceuticals, for example, as vaccines. Biologics are usually produced in bacterial, mammalian or insect cells. Alternatively, plant molecular farming, that is, the manufacture of biologics in plant cells, transgenic plants and algae, offers a cheaper and easily adaptable strategy for the production of biologics, in particular, in low- resource settings. In this Review, we discuss current vaccination challenges, such as cold chain requirements, and highlight how plant molecular farming in combination with advanced materials can be applied to address these challenges. The production of plant viruses and virus- based nanotechnologies in plants enables low- cost and regional fabrication of thermostable vaccines. We also highlight key new vaccine delivery technologies, including microneedle patches and material platforms for intranasal and oral delivery. Finally, we provide an outlook of future possibilities for plant molecular farming of next- generation vaccines and biologics.
5. Analysis of the potential efficacy and timing of COVID-19 vaccine on morbidity and mortality

   Haghpanah, F ; Lin, G ; Levin, SA ; Klein, E. ( January 2021 , EClinicalMedicine)

   Background: COVID-19 vaccines have been approved and made available. While questions of vaccine allocation strategies have received significant attention, important questions remain regarding the potential impact of the vaccine given uncertainties regarding efficacy against transmission, availability, timing, and durability. Methods: We adapted a susceptible-exposed-infectious-recovered (SEIR) model to examine the potential impact on hospitalization and mortality assuming increasing rates of vaccine efficacy, coverage, and administration. We also evaluated the uncertainty of the vaccine to prevent infectiousness as well as the impact on outcomes based on the timing of distribution and the potential effects of waning immunity. Findings: Increased vaccine efficacy against disease reduces hospitalizations and deaths from COVID-19; however, the relative benefit of transmission blocking varied depending on the timing of vaccine distribution. Early in an outbreak, a vaccine that reduces transmission will be relatively more effective than one introduced later in the outbreak. In addition, earlier and accelerated implementation of a less effective vaccine is more impactful than later implementation of a more effective vaccine. These findings are magnified when considering the durability of the vaccine. Vaccination in the spring will be less impactful when immunity is less durable. Interpretation: Policy choices regarding non-pharmaceutical interventions, such as social distancing andmore »face mask use, will need to remain in place longer if the vaccine is less effective at reducing transmission or distributed slower. In addition, the stage of the local outbreak greatly impacts the overall effectiveness of the vaccine in a region and should be considered when allocating vaccines.« less