Pathogenicity Factors of Anaplasma phagocytophilum (Review)
DOI:
https://doi.org/10.37482/2687-1491-Z286Keywords:
Anaplasma phagocytophilum, electroneuromyography, neutrophil, type IV secretion system, effector proteins, intracellular persistence, apoptosis, autophagyAbstract
Human granulocytic anaplasmosis is a natural-focal vector-borne infection caused by the obligate intracellular pathogen Anaplasma phagocytophilum. The relevance of this study is due to the growing interest in the pathogenesis of anaplasmosis and the virulence factors of its causative agent amid increasing attention to natural- focal infections worldwide. The pathogen forms morulae in neutrophils and maintains intracellular persistence by reprogramming host cell signaling and regulatory pathways, thereby bypassing innate antibacterial defense mechanisms. The aim of this review is to systematize current concepts of the molecular mechanisms of A. phagocytophilum pathogenicity and its effector proteins. Original articles and reviews, selected from the PubMed, Elsevier, and CyberLeninka databases, are analyzed. Priority is given to publications over the last 10 years, while fundamental studies that first described the pathogen, the clinical characteristics of Anaplasma infection, and key effector mechanisms are included regardless of the date of publication. A total of 50 sources are included in the review. Particular attention is paid to experimental data on the AnkA, Ats-1, and AptA proteins, their interactions with cellular targets, and their effects on apoptosis, transcription, mitochondrial pathways, and signaling pathways. The mechanism of A. phagocytophilum survival in the host is considered, which involves the invasion of immune system cells and alteration of their functioning. Using the AnkA, Ats-1, and AptA proteins, the bacterium suppresses natural cell death (apoptosis), blocks the production of reactive oxygen species, and disrupts intracellular protein signaling. This enables the pathogen to persist in the host for a long time while avoiding elimination by the immune system. Pathogenic proteins are delivered into the host cell via the type IV secretion system, which is characteristic of a number of intracellular pathogens. Understanding the role of A. phagocytophilum effector proteins in the pathogenesis of anaplasmosis may provide a basis for the development of new diagnostic methods for this disease, targeted therapy, and epidemiological surveillance, especially in regions with natural nidality.
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