Exit strategies of intracellular pathogens

Hybiske, Kevin; Stephens, Richard S.

doi:10.1038/nrmicro1821

Cited by 130 publications

(111 citation statements)

References 104 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…Several of the R. parkeri proteins that we identified have been implicated in the virulence of other Rickettsia spp. The WASP N-WASP MENA proteins or RickA are involved in actin-based motility through activation of the Arp2/3 complex utilized by SFGR to exit from the host cell (15,18,19). The ability of R. parkeri to form actin tails was reported by Heinzen et al (17).…”

Section: Discussionmentioning

confidence: 98%

Proteomic Analysis of Rickettsia parkeri Strain Portsmouth

et al. 2009

View full text Add to dashboard Cite

Rickettsia parkeri, a recently recognized pathogen of human, is one of several Rickettsia spp. in the United States that causes a spotted fever rickettsiosis. To gain insights into its biology and pathogenesis, we applied the proteomics approach to establish a two-dimensional gel proteome reference map and combined this technique with cell surface biotinylation to identify surface-exposed proteins of a low-passage isolate of R. parkeri obtained from a patient. We identified 91 proteins by matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry. Of these, 28 were characterized as surface proteins, including virulence-related proteins (e.g., outer membrane protein A [OmpA], OmpB, ␤-peptide, and RickA). Two-dimensional immunoblotting with serum from the R. parkeri-infected index patient was utilized to identify the immunoreactive proteins as potential targets for diagnosis and vaccine development. In addition to the known rickettsial antigens, OmpA and OmpB, we identified translation initiation factor 2, cell division protein FtsZ, and cysteinyl-tRNA synthetase as immunoreactive proteins. The proteome map with corresponding cell surface protein analysis and antigen detection will facilitate a better understanding of the mechanisms of rickettsial pathogenesis.Rickettsia parkeri, a member of the spotted fever group Rickettsia (SFGR), was first isolated from the Gulf Coast tick, Amblyomma maculatum, in 1937 (29). In 2004, the first confirmed human infection with R. parkeri was reported in a 40-year-old man from the Tidewater area of coastal Virginia. The agent was isolated in cell culture from an eschar biopsy specimen and designated the Portsmouth strain (28). Recently, the first recognized case of tick bite-associated human infection was described (43); however, the epidemiology of R. parkeri is not well defined. In the United States, R. parkeri has been detected in A. maculatum and A. americanum; the geographical overlap between R. parkeri and these ticks with that of the vectors of R. rickettsii (the etiological agent of Rocky Mountain spotted fever [RMSF]) suggests that many cases of R. parkeri infection have been misidentified as RMSF (27,35). For example, Western blot analysis of serum specimens from 15 U.S. patients previously diagnosed with RMSF identified four serum specimens reactive with a 120-kDa protein of R. parkeri, suggesting infection with R. parkeri rather than R. rickettsii (30). However, a serologic test specific for this pathogen is not available (43), and little is known about its biology.Due to their obligate intracellular nature, genetic manipulation of Rickettsia has proven difficult. Alternatively, protein expression profiles (proteomes) are utilized to identify the mechanisms of pathogenesis and differentiate rickettsial species recognizing host immune response specificity to cell surface molecules, referred to as outer membrane proteins (Omps). The presence or absence of some Omps allows for differentiation between the typhus group and the SFGR, and the response...

show abstract

Section: Discussionmentioning

confidence: 98%

Proteomic Analysis of Rickettsia parkeri Strain Portsmouth

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Although host cell egress by different pathogens sometimes needs to meet very different requirements, the various strategies share some common principles. From what is known to date, it appears that most eukaryotic intracellular parasites have opted for a lytic egress strategy, which might simply be due to their relatively large sizes compared to the sizes of bacteria, for which nonlytic egress strategies are more common (76). As a consequence, these pathogens need to be prepared to face the hostile extracellular environment.…”

Section: Discussionmentioning

confidence: 99%

“…Protrusion mechanisms play an important role in the egress of prokaryotic intracellular pathogens (28,76). Protrusion induced by Listeria and Shigella has been extensively described and relies on the polymerization of host cell actin on the bacterial surface.…”

Section: Strategies For Nonlytic Egress From the Cytosol Protrusion Amentioning

confidence: 99%

Prison Break: Pathogens' Strategies To Egress from Host Cells

Friedrich

Hagedorn

Soldati‐Favre

et al. 2012

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYA wide spectrum of pathogenic bacteria and protozoa has adapted to an intracellular life-style, which presents several advantages, including accessibility to host cell metabolites and protection from the host immune system. Intracellular pathogens have developed strategies to enter and exit their host cells while optimizing survival and replication, progression through the life cycle, and transmission. Over the last decades, research has focused primarily on entry, while the exit process has suffered from neglect. However, pathogen exit is of fundamental importance because of its intimate association with dissemination, transmission, and inflammation. Hence, to fully understand virulence mechanisms of intracellular pathogens at cellular and systemic levels, it is essential to consider exit mechanisms to be a key step in infection. Exit from the host cell was initially viewed as a passive process, driven mainly by physical stress as a consequence of the explosive replication of the pathogen. It is now recognized as a complex, strategic process termed “egress,” which is just as well orchestrated and temporally defined as entry into the host and relies on a dynamic interplay between host and pathogen factors. This review compares egress strategies of bacteria, pathogenic yeast, and kinetoplastid and apicomplexan parasites. Emphasis is given to recent advances in the biology of egress in mycobacteria and apicomplexans.

show abstract

“…Although pathogen exit is not as well understood as pathogen entry, there are a variety of exit strategies that have been described recently, including both lytic and nonlytic egress from host cells (1,2). These studies in tissue culture cells have identified a diversity of host pathways and processes in pathogen exit.…”

mentioning

confidence: 99%

The small GTPase RAB-11 directs polarized exocytosis of the intracellular pathogen N. parisii for fecal-oral transmission from C. elegans

Szumowski

Botts

Popovich

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Pathogen exit is a key stage in the spread and propagation of infectious disease, with the fecal-oral route being a common mode of disease transmission. However, it is poorly understood which molecular pathways provide the major modes for intracellular pathogen exit and fecal-oral transmission in vivo. Here, we use the transparent nematode Caenorhabditis elegans to investigate intestinal cell exit and fecal-oral transmission by the natural intracellular pathogen Nematocida parisii, which is a recently identified species of microsporidia. We show that N. parisii exits from polarized host intestinal cells by co-opting the host vesicle trafficking system and escaping into the lumen. Using a genetic screen, we identified components of the host endocytic recycling pathway that are required for N. parisii spore exit via exocytosis. In particular, we show that the small GTPase RAB-11 localizes to apical spores, is required for spore-containing compartments to fuse with the apical plasma membrane, and is required for spore exit. In addition, we find that RAB-11-deficient animals exhibit impaired contagiousness, supporting an in vivo role for this host trafficking factor in microsporidia disease transmission. Altogether, these findings provide an in vivo example of the major mode of exit used by a natural pathogen for disease spread via fecal-oral transmission.

show abstract

Exit strategies of intracellular pathogens

Cited by 130 publications

References 104 publications

Proteomic Analysis of Rickettsia parkeri Strain Portsmouth

Proteomic Analysis of Rickettsia parkeri Strain Portsmouth

Prison Break: Pathogens' Strategies To Egress from Host Cells

The small GTPase RAB-11 directs polarized exocytosis of the intracellular pathogen N. parisii for fecal-oral transmission from C. elegans

Contact Info

Product

Resources

About