Type IV secretion in the obligatory intracellular bacterium Anaplasma phagocytophilum
Yasuko Rikihisa1, Mingqun Lin, Hua Niu
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. rikihisa.1@osu.edu
Abstract:
Anaplasma phagocytophilum is an obligatory intracellular bacterium that infects neutrophils, the primary host defence cells. Consequent effects of infection on host cells result in a potentially fatal systemic disease called human granulocytic anaplasmosis. Despite ongoing reductive genome evolution and deletion of most genes for intermediary metabolism and amino acid biosynthesis, Anaplasma has also experienced expansion of genes encoding several components of the type IV secretion (T4S) apparatus. Two A. phagocytophilum T4S effector molecules are currently known; Anaplasma translocated substrate 1 (Ats-1) and ankyrin repeat domain-containing protein A (AnkA) have C-terminal positively charged amino acid residues that are recognized by the T4S coupling protein, VirD4. AnkA and Ats-1 contain eukaryotic protein motifs and are uniquely evolved in the family Anaplasmataceae; Ats-1 contains a mitochondria-targeting signal. They are abundantly produced and secreted into the host cytoplasm, are not toxic to host cells, and manipulate host cell processes to aid in the infection process. At the cellular level, the two effectors have distinct subcellular localization and signalling in host cells. Thus in this obligatory intracellular pathogen, the T4S system has evolved as a host-subversive survival factor.
Insights
Anaplasma phagocytophilum uses a type IV secretion system to inject effector proteins into host cells, aiding its survival and manipulation of host defenses during infection. This mechanism is crucial for the bacterium
Area of Science:
- Microbiology
- Cellular Biology
- Pathogen-Host Interactions
Background:
- Anaplasma phagocytophilum is an intracellular bacterium causing human granulocytic anaplasmosis.
- The bacterium infects neutrophils, critical host defense cells.
- Despite genome reduction, Anaplasma has expanded its type IV secretion (T4S) system genes.
Purpose of the Study:
- To investigate the role of the T4S system and its effector proteins in Anaplasma phagocytophilum pathogenesis.
- To understand how Anaplasma manipulates host cells for survival and replication.
Main Methods:
- Analysis of Anaplasma phagocytophilum genome evolution, focusing on T4S apparatus genes.
- Identification and characterization of T4S effector proteins, Ats-1 and AnkA.
- Investigation of effector protein secretion, localization, and function within host cells.
Main Results:
- Anaplasma phagocytophilum possesses an expanded T4S system, crucial for pathogenesis.
- Two effector proteins, Ats-1 and AnkA, are secreted into the host cytoplasm.
- These effectors possess eukaryotic motifs, manipulate host cell processes, and exhibit distinct subcellular localizations.
Conclusions:
- The T4S system is a key survival factor for Anaplasma phagocytophilum, enabling host cell manipulation.
- Effector proteins Ats-1 and AnkA play distinct roles in subverting host cell functions.
- Understanding these mechanisms provides insights into treating anaplasmosis.
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