Targeted mutagenesis in Anaplasma marginale to define virulence and vaccine development against bovine anaplasmosis

Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted mutagenesis methods are yet to be developed to define genes essential for these pathogens. In addition, vaccines conferring protect...

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Bibliographic Details
Published in:	PLoS pathogens Vol. 18; no. 5; p. e1010540
Main Authors:	Hove, Paidashe, Madesh, Swetha, Nair, Arathy, Jaworski, Deborah, Liu, Huitao, Ferm, Jonathan, Kleinhenz, Michael D, Highland, Margaret A, Curtis, Andrew K, Coetzee, Johann F, Noh, Susan M, Wang, Ying, Genda, Dominica, Ganta, Roman R
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01-05-2022 Public Library of Science (PLoS)
Subjects:	Anaplasma Anaplasma marginale Anaplasma marginale - genetics Anaplasmosis Anaplasmosis - genetics Anaplasmosis - prevention & control Anemia Animals Antigens Arachnids Biology and Life Sciences Cattle Cattle Diseases - microbiology Cell size Dairy cattle Disease Disease control Dogs Enzymes Erythrocytes Gene deletion Gene mutations Genes Genetic aspects Genomes Health aspects Host-parasite relationships Humans Identification and classification In vivo methods and tests Infections Medicine and Health Sciences Microscopy Mutagenesis Mutants Mutation Pathogens Phages Prevention Research and Analysis Methods Site-directed mutagenesis Species Targeted mutagenesis Vaccine Development Vaccines Viral proteins Virulence Virulence (Microbiology) United States United States > US
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Summary:	Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted mutagenesis methods are yet to be developed to define genes essential for these pathogens. In addition, vaccines conferring protection against diseases caused by Anaplasma species are not available. Here, we describe a targeted mutagenesis method for deletion of the phage head-to-tail connector protein (phtcp) gene in Anaplasma marginale. The mutant did not cause disease and exhibited attenuated growth in its natural host (cattle). We then assessed its ability to confer protection against wild-type A. marginale infection challenge. Additionally, we compared vaccine protection with the mutant to that of whole cell A. marginale inactivated antigens as a vaccine (WCAV) candidate. Upon infection challenge, non-vaccinated control cattle developed severe disease, with an average 57% drop in packed cell volume (PCV) between days 26-31 post infection, an 11% peak in erythrocytic infection, and apparent anisocytosis. Conversely, following challenge, all animals receiving the live mutant did not develop clinical signs or anemia, or erythrocyte infection. In contrast, the WCAV vaccinees developed similar disease as the non-vaccinees following A. marginale infection, though the peak erythrocyte infection reduced to 6% and the PCV dropped 43%. This is the first study describing targeted mutagenesis and its application in determining in vivo virulence and vaccine development for an Anaplasma species pathogen. This study will pave the way for similar research in related Anaplasma pathogens impacting multiple hosts.
Bibliography:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1010540