Moonlighting in Rickettsiales: Expanding Virulence Landscape

Abstract

The order Rickettsiales includes species that cause a range of human diseases such as human granulocytic anaplasmosis (Anaplasma phagocytophilum), human monocytic ehrlichiosis (Ehrlichia chaffeensis), scrub typhus (Orientia tsutsugamushi), epidemic typhus (Rickettsia prowazekii), murine typhus (R. typhi), Mediterranean spotted fever (R. conorii), or Rocky Mountain spotted fever (R. rickettsii). These diseases are gaining a new momentum given their resurgence patterns and geographical expansion due to the overall rise in temperature and other human-induced pressure, thereby remaining a major public health concern. As obligate intracellular bacteria, Rickettsiales are characterized by their small genome sizes due to reductive evolution. Many pathogens employ moonlighting/multitasking proteins as virulence factors to interfere with multiple cellular processes, in different compartments, at different times during infection, augmenting their virulence. The utilization of this multitasking phenomenon by Rickettsiales as a strategy to maximize the use of their reduced protein repertoire is an emerging theme. Here, we provide an overview of the role of various moonlighting proteins in the pathogenicity of these species. Despite the challenges that lie ahead to determine the multiple potential faces of every single protein in Rickettsiales, the available examples anticipate this multifunctionality as an essential and intrinsic feature of these obligates and should be integrated into available moonlighting repositories.

Cortactin: A universal host cytoskeletal target of Gram‐negative and Gram‐positive bacterial pathogens

“…Rickettsia conorii is a Gram‐negative, obligate intracellular bacterium and causes boutonneuse fever (Matos et al, 2022). The bacterium is taken up by the host cell followed by intracellular motility using actin tails (Gouin et al, 1999; Martinez & Cossart, 2004).…”

The Obligate Intracellular Bacterial Pathogen Anaplasma phagocytophilum Exploits Host Cell Multivesicular Body Biogenesis for Proliferation and Dissemination

“… Anaplasma phagocytophilum is an Ixodes spp. tick-transmitted obligate intracellular bacterium that proliferates in membrane-bound inclusions of neutrophils and bone marrow progenitor cells ( 1 , 2 ). A. phagocytophilum infection in humans, termed human granulocytic anaplasmosis (HGA), is the second-most common tickborne disease in the United States and occurs throughout much of Europe and Asia ( 3 , 4 ).…”

Genomic characters of Anaplasma bovis and genetic diversity in China

“…AnkA is an effector protein of T4SS that can bind a large number of DNA and proteins and may be involved in regulating neutrophils survival and replication. Phosphorylated AnkA interacts with SHP-1 to interfere with host cell signalling and may promote the survival of A. phagocytophilum [ 49–51 ]. OmpA facilitates pathogen invasion of mammalian and tick host cells, and anti-OmpA serum treated A. phagocytophilum reduced the ability to infect HL-60 cells [ 52 , 53 ].…”