Isolation of ClpB & DnaK bi-chaperones from obligate pathogen Anaplasma phagocytophilum as future therapeutic targets

Abstract

Anaplasma phagocytophilum is an obligate intracellular pathogen that causes Human Granulocytic Anaplasmosis (HGA). Genetic manipulation of obligate intracellular pathogens is extremely difficult, as these organisms possess small genomes made primarily of essential genes and rely significantly on the host cell for proliferation. To date, only a handful of genetic tools have been developed to study the pathobiology of Anaplasma, and doxycycline remains the only available treatment for HGA. ClpB and DnaK are molecular chaperones responsible for reactivating and resolubilizing protein aggregates within the cellular environment. Recently, ClpB has emerged as a promising target for the development of novel antimicrobials, as it is essential for the survival of many pathogens and lacks apparent orthologs in metazoans. Initial findings indicate that these chaperones have different substrate preferences, despite being almost identical across different species, providing a unique approach to develop novel therapeutics against specific species.