Infection by Microsporidia Disrupts the Host Cell Cycle

Abstract

ABSTRACT. Microsporidia of the genus Encephalitozoon infect mammalian cells and have become a source of morbidity and mortality in immunocompromised humans. Encephalitozoon microsporidia develop and mature within parasitophorous vacuoles, enlarging the vacuole over time until it eventually occupies most of the cytoplasm of the host cell. The ability of the host cell to accommodate such a large burden for several days suggests that the parasite subverts normal host cell processes to ensure optimal environmental conditions for its growth and development. Since this environment would be threatened if cell division of the host cell occurred, we have formulated the hypothesis that infection with Encephalitozoon microsporidia induces an arrest in the cell cycle of the host cell. In support of this hypothesis, we have found that mitotic index and DNA duplication are reduced in infected cells as compared to uninfected cells. The number of host cell nuclei in S phase is increased. The levels of cyclin D1 and the percentage of cells in G1 are reduced; however, the levels of cyclin B1 are elevated even though the percentage of cells in G2/M is decreased. These results suggest that host cells infected with Encephalitozoon microsporidia are blocked at multiple points in the cell cycle.

Multinucleate host cells induced by Vittaforma corneae (Microsporidia)

“…While there is only limited information available on the effects of microsporidial infection on the cell cycle, that which is available favours the inhibition of host cell mitosis (e.g. Scanlon et al 2000). On the other hand, if cell fusion was the cause of the multinucleate cells, one would expect to have seen examples of partial fusion, which we did not observe.…”

“…As obligate intracellular parasites the microsporidia appear to have been able to reduce their genome size, simplify their organelle structures and reduce their biochemical pathways by subverting the host cell's physiology to provide the missing biochemical support for parasite development (Slamovits et al 2004). As with other intracellular parasites, from viruses to protozoa (e.g., Halonen and Weidner 1994, Risco et al 2002, Grieshaber et al 2003, the microsporidia appear to modify host cell cytoskeleton, organelle arrangement, biochemistry and cell cycle to optimize the intracellular niche (Weidner et al 1999, Scanlon et al 2000. To date, compared with many other infectious agents, relatively little is known about how the microsporidia signal the host cells to affect these many changes that occur in host cell structure and function.…”

Neisseria gonorrhoeae infection causes DNA damage and affects the expression of p21, p27 and p53 in non-tumor epithelial cells

“…The regulation of CDK-cyclin complex activity occurs through cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, at checkpoints that halt the cell cycle in response to unreplicated or damaged DNA, which allows time for repair or apoptosis (Vermeulen et al, 2003). Cellular damage has been recognized to occur during bacterial infections (Kundu and Surh, 2008), and microbial pathogens have developed a variety of strategies to manipulate host cell functions, including the release of toxins that inhibit or promote cell cycle progression (Lara-Tejero and Galán, 2000;Nougayrède et al, 2005;Oswald et al, 2005), associate with host cell microtubules (Hu and Kopecko, 1999), or block multiple checkpoints in the cell cycle (Scanlon et al, 2000).…”

In Vitro Alterations Do Not Reflect a Requirement for Host Cell Cycle Progression during Plasmodium Liver Stage Infection

“…While important and well-studied examples arise from viral and bacterial infections (reviewed in references 1 and 2), protozoan parasites, such as Toxoplasma gondii (3)(4)(5), Trypanosoma cruzi (6), Eimeria bovis (7), Encephalitozoon spp. (8), and Leishmania major (9), have all been suggested to modulate host cell cycle progression. Perhaps the most striking example of dependence on host cell cycle progression in protozoan parasites comes from the apicomplexans Theileria annulata and Theileria parva, which ensure their own propagation by transforming the lymphocytes and monocytes they infect (reviewed in reference 10).…”