<i>Anaplasma phagocytophilum</i>APH_1387 Is Expressed throughout Bacterial Intracellular Development and Localizes to the Pathogen-Occupied Vacuolar Membrane

Huang, Bernice; Troese, Matthew J.; Ye, Shaojing; Sims, Jonathan T.; Galloway, Nathan L.; Borjesson, Dori L.; Carlyon, Jason A.

doi:10.1128/iai.01418-09

Cited by 36 publications

(88 citation statements)

References 57 publications

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“…We detected expression of 27 hypothetical proteins in tick salivary glands by proteomics or RNA-seq (Table 3 and Table 4). Some of these proteins have previously been characterized in HL-60 cultures for their roles in A. phagocytophilum infection (14,15,34) or identified as immunoreactive proteins (24). Two hypothetical proteins, APH_0220 and APH_0792, were classified as among the most abundant in the HL-60 culture proteome (23).…”

Section: Resultsmentioning

confidence: 99%

Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice

2012

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Obligate intracellular bacteria of the Rickettsiales order have evolved to colonize both arthropod and mammalian hosts, but few details are known about the bacterial adaptations that occur during transmission from blood-feeding arthropods to mammals. Here we apply proteomics and transcriptome sequencing to Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, in Ixodes scapularis tick salivary glands, to detect proteins or genes expressed by the pathogen during transmission feeding by the tick. We detected expression of 139 genes, representing 11% of the open reading frames (ORFs) in the A. phagocytophilum genome. The predominant categories of proteins were ribosomal proteins, cell surface proteins, chaperones, and uncharacterized proteins. There was no evidence of DNA replication enzymes, suggesting that most of the A. phagocytophilum cells were no longer dividing. Instead, protein expression reflected conversion to the extracellular, infectious "dense-core" (DC) form. High expression of a DC-specific marker, APH_1235, further suggested this developmental transition in ticks. We showed that blocking APH_1235 with antibodies reduced A. phagocytophilum infection levels in mammalian cell culture. This work represents a starting point for clarifying essential proteins expressed by A. phagocytophilum during transmission from ticks to mammals and demonstrates that the abundantly expressed, DC-associated APH_1235 protein is important during in vivo infection by A. phagocytophilum.

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Section: Resultsmentioning

confidence: 99%

Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice

2012

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“…As expected, no association with the inclusion membrane was observed for the protein pc0577, which is consistent with the observed cytoplasmic signal with these antibodies in the immunofluorescence experiments. (54), and similar proteins have only rarely been identified in other bacteria (28,53). Located directly at the interface between bacteria and host cell, the inclusion membrane is a central mediator for interaction with and manipulation of the host cell by the chlamydiae.…”

Section: Resultsmentioning

confidence: 99%

Inclusion Membrane Proteins ofProtochlamydia amoebophilaUWE25 Reveal a Conserved Mechanism for Host Cell Interaction among theChlamydiae

et al. 2010

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Chlamydiae are a group of obligate intracellular bacteria comprising several important human pathogens. Inside the eukaryotic cell, chlamydiae remain within a host-derived vesicular compartment, termed the inclusion. They modify the inclusion membrane through insertion of unique proteins, which are involved in interaction with and manipulation of the host cell. Among chlamydiae, inclusion membrane proteins have been exclusively found in members of the family Chlamydiaceae, which predominantly infect mammalian and avian hosts. Here, the presence of inclusion membrane proteins in Protochlamydia amoebophila UWE25, a chlamydial endosymbiont of free-living amoebae, is reported. A genome-wide screening for secondary structure motifs resulted in the identification of 23 putative inclusion membrane proteins for this organism. Immunofluorescence analysis demonstrated that five of these proteins were expressed, and four of them could be localized to a halo surrounding the intracellular bacteria. Colocalization studies showed an almost complete overlap of the signals obtained for the four putative inclusion membrane proteins, and immuno-transmission electron microscopy unambiguously demonstrated their location in the inclusion membrane. The presence of inclusion membrane proteins (designated IncA, IncQ, IncR, and IncS) in P. amoebophila shows that this strategy for host cell interaction is conserved among the chlamydiae and is used by chlamydial symbionts and pathogens alike.Chlamydiae were once considered a small group of very closely related bacteria which form an evolutionarily well-separated lineage in the tree of life. These obligate intracellular bacteria infect a broad spectrum of at least 60 eukaryotic host organisms including both invertebrates and vertebrates. Until recently, the family Chlamydiaceae was the only described chlamydial family, which is exclusively comprised of human and animal pathogens. It includes Chlamydia trachomatis, the most prevalent sexually transmitted bacteria worldwide, with over 90 million new cases of infection per year (56), and the world's leading cause of preventable blindness (57). The other major human pathogen among the chlamydiae, Chlamydophila pneumoniae (basonym, Chlamydia pneumoniae) (15), causes community-acquired pneumonia and is also implicated in several chronic diseases such as arteriosclerosis and multiple sclerosis (33, 38). The discovery of several chlamydia-like endosymbionts in amoebae in the late 1990s represented the first evidence for a much larger diversity of chlamydiae in the environment (3,7,17,27). Since then, numerous new chlamydial organisms were discovered, which led to the description of several new families (9,25,30).A characteristic feature of all chlamydiae is the developmental cycle, which includes morphologically and physiologically distinct developmental forms (1, 37). Infection of host cells starts with the attachment of the infectious form of the chlamydiae, the elementary body (EB), to a host cell and uptake by a phagocytosis-like mechanism. Onc...

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“…(132). Several hypothetical proteins in A. phagocytophilum were found to be surface-exposed proteins, inclusion membrane proteins, and T4S substrates that confer unique phenotypes to this bacterium (74,99,100,166,195,210). A. phagocytophilum and Rickettsia prowazekii share 469 genes (61), and both bacteria cannot use glucose as a carbon or energy source.…”

Section: Genomic Featuresmentioning

confidence: 99%

Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum

2011

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SUMMARY Anaplasma phagocytophilum persists in nature by cycling between mammals and ticks. Human infection by the bite of an infected tick leads to a potentially fatal emerging disease called human granulocytic anaplasmosis. A. phagocytophilum is an obligatory intracellular bacterium that replicates inside mammalian granulocytes and the salivary gland and midgut cells of ticks. A. phagocytophilum evolved the remarkable ability to hijack the regulatory system of host cells. A. phagocytophilum alters vesicular traffic to create an intracellular membrane-bound compartment that allows replication in seclusion from lysosomes. The bacterium downregulates or actively inhibits a number of innate immune responses of mammalian host cells, and it upregulates cellular cholesterol uptake to acquire cholesterol for survival. It also upregulates several genes critical for the infection of ticks, and it prolongs tick survival at freezing temperatures. Several host factors that exacerbate infection have been identified, including interleukin-8 (IL-8) and cholesterol. Host factors that overcome infection include IL-12 and gamma interferon (IFN-γ). Two bacterial type IV secretion effectors and several bacterial proteins that associate with inclusion membranes have been identified. An understanding of the molecular mechanisms underlying A. phagocytophilum infection will foster the development of creative ideas to prevent or treat this emerging tick-borne disease.

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Anaplasma phagocytophilumAPH_1387 Is Expressed throughout Bacterial Intracellular Development and Localizes to the Pathogen-Occupied Vacuolar Membrane

Cited by 36 publications

References 57 publications

Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice

Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice

Inclusion Membrane Proteins ofProtochlamydia amoebophilaUWE25 Reveal a Conserved Mechanism for Host Cell Interaction among theChlamydiae

Mechanisms of Obligatory Intracellular Infection with Anaplasma phagocytophilum

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