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1. Toxoplasma TgATG9 is critical for autophagy and long-term persistence in tissue cysts

Author

David Smith, Geetha Kannan, Isabelle Coppens, Fengrong Wang, Hoa Mai Nguyen, Aude Cerutti, Einar B Olafsson, Patrick A Rimple, Tracey L Schultz, Nayanna M Mercado Soto, Manlio Di Cristina, Sébastien Besteiro, and Vern B Carruthers

Subjects
Toxoplasma gondii, chronic infection, ATG9, apicomplexa, protozoan, parasite, Medicine, Science, Biology (General), QH301-705.5
Abstract

Many of the world’s warm-blooded species are chronically infected with Toxoplasma gondii tissue cysts, including an estimated one-third of the global human population. The cellular processes that permit long-term persistence within the cyst are largely unknown for T. gondii and related coccidian parasites that impact human and animal health. Herein, we show that genetic ablation of TgATG9 substantially reduces canonical autophagy and compromises bradyzoite viability. Transmission electron microscopy revealed numerous structural abnormalities occurring in ∆atg9 bradyzoites. Intriguingly, abnormal mitochondrial networks were observed in TgATG9-deficient bradyzoites, some of which contained numerous different cytoplasmic components and organelles. ∆atg9 bradyzoite fitness was drastically compromised in vitro and in mice, with very few brain cysts identified in mice 5 weeks post-infection. Taken together, our data suggests that TgATG9, and by extension autophagy, is critical for cellular homeostasis in bradyzoites and is necessary for long-term persistence within the cyst of this coccidian parasite.

Published
2021
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2. Tales of diversity: Genomic and morphological characteristics of forty-six Arthrobacter phages.

Author

Karen K Klyczek, J Alfred Bonilla, Deborah Jacobs-Sera, Tamarah L Adair, Patricia Afram, Katherine G Allen, Megan L Archambault, Rahat M Aziz, Filippa G Bagnasco, Sarah L Ball, Natalie A Barrett, Robert C Benjamin, Christopher J Blasi, Katherine Borst, Mary A Braun, Haley Broomell, Conner B Brown, Zachary S Brynell, Ashley B Bue, Sydney O Burke, William Casazza, Julia A Cautela, Kevin Chen, Nitish S Chimalakonda, Dylan Chudoff, Jade A Connor, Trevor S Cross, Kyra N Curtis, Jessica A Dahlke, Bethany M Deaton, Sarah J Degroote, Danielle M DeNigris, Katherine C DeRuff, Milan Dolan, David Dunbar, Marisa S Egan, Daniel R Evans, Abby K Fahnestock, Amal Farooq, Garrett Finn, Christopher R Fratus, Bobby L Gaffney, Rebecca A Garlena, Kelly E Garrigan, Bryan C Gibbon, Michael A Goedde, Carlos A Guerrero Bustamante, Melinda Harrison, Megan C Hartwell, Emily L Heckman, Jennifer Huang, Lee E Hughes, Kathryn M Hyduchak, Aswathi E Jacob, Machika Kaku, Allen W Karstens, Margaret A Kenna, Susheel Khetarpal, Rodney A King, Amanda L Kobokovich, Hannah Kolev, Sai A Konde, Elizabeth Kriese, Morgan E Lamey, Carter N Lantz, Jonathan S Lapin, Temiloluwa O Lawson, In Young Lee, Scott M Lee, Julia Y Lee-Soety, Emily M Lehmann, Shawn C London, A Javier Lopez, Kelly C Lynch, Catherine M Mageeney, Tetyana Martynyuk, Kevin J Mathew, Travis N Mavrich, Christopher M McDaniel, Hannah McDonald, C Joel McManus, Jessica E Medrano, Francis E Mele, Jennifer E Menninger, Sierra N Miller, Josephine E Minick, Courtney T Nabua, Caroline K Napoli, Martha Nkangabwa, Elizabeth A Oates, Cassandra T Ott, Sarah K Pellerino, William J Pinamont, Ross T Pirnie, Marie C Pizzorno, Emilee J Plautz, Welkin H Pope, Katelyn M Pruett, Gabbi Rickstrew, Patrick A Rimple, Claire A Rinehart, Kayla M Robinson, Victoria A Rose, Daniel A Russell, Amelia M Schick, Julia Schlossman, Victoria M Schneider, Chloe A Sells, Jeremy W Sieker, Morgan P Silva, Marissa M Silvi, Stephanie E Simon, Amanda K Staples, Isabelle L Steed, Emily L Stowe, Noah A Stueven, Porter T Swartz, Emma A Sweet, Abigail T Sweetman, Corrina Tender, Katrina Terry, Chrystal Thomas, Daniel S Thomas, Allison R Thompson, Lorianna Vanderveen, Rohan Varma, Hannah L Vaught, Quynh D Vo, Zachary T Vonberg, Vassie C Ware, Yasmene M Warrad, Kaitlyn E Wathen, Jonathan L Weinstein, Jacqueline F Wyper, Jakob R Yankauskas, Christine Zhang, and Graham F Hatfull

Subjects
Medicine, Science
Abstract

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.

Published
2017
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