Toxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycle

dc.contributor.authorSrivastava, Sandeep
dc.contributor.authorWhite, Michael W.
dc.contributor.authorSullivan, William J., Jr.
dc.contributor.departmentPharmacology and Toxicology, School of Medicineen_US
dc.date.accessioned2021-05-26T20:40:12Z
dc.date.available2021-05-26T20:40:12Z
dc.date.issued2020-10-01
dc.description.abstractToxoplasma gondii is a protozoan parasite that causes lifelong chronic infection that can reactivate in immunocompromised individuals. Upon infection, the replicative stage (tachyzoite) converts into a latent tissue cyst stage (bradyzoite). Like other apicomplexans, T. gondii possesses an extensive lineage of proteins called ApiAP2s that contain DNA-binding domains first characterized in plants. The function of most ApiAP2s is unknown. We previously found that AP2IX-4 is a cell cycle-regulated ApiAP2 expressed only in dividing parasites as a putative transcriptional repressor. In this study, we purified proteins interacting with AP2IX-4, finding it to be a component of the recently characterized microrchidia (MORC) transcriptional repressor complex. We further analyzed AP2XII-2, another cell cycle-regulated factor that associates with AP2IX-4. We monitored parallel expression of AP2IX-4 and AP2XII-2 proteins in tachyzoites, detecting peak expression during S/M phase. Unlike AP2IX-4, which is dispensable in tachyzoites, loss of AP2XII-2 resulted in a slowed tachyzoite growth due to a delay in S-phase progression. We also found that AP2XII-2 depletion increased the frequency of bradyzoite differentiation in vitro. These results suggest that multiple AP2 factors collaborate to ensure proper cell cycle progression and tissue cyst formation in T. gondii. IMPORTANCE Toxoplasma gondii is a single-celled parasite that persists in its host by converting into a latent cyst stage. This work describes a new transcriptional factor called AP2XII-2 that plays a role in properly maintaining the growth rate of replicating parasites, which contributes to signals required for development into its dormant stage. Without AP2XII-2, Toxoplasma parasites experience a delay in their cell cycle that increases the frequency of latent cyst formation. In addition, we found that AP2XII-2 operates in a multisubunit complex with other AP2 factors and chromatin remodeling machinery that represses gene expression. These findings add to our understanding of how Toxoplasma parasites balance replication and dormancy, revealing novel points of potential therapeutic intervention to disrupt this clinically relevant process.en_US
dc.identifier.citationSrivastava, S., White, M. W., & Sullivan, W. J. (2020). Toxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycle. MSphere, 5(5). https://doi.org/10.1128/mSphere.00542-20en_US
dc.identifier.issn2379-5042en_US
dc.identifier.urihttps://hdl.handle.net/1805/26027
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.isversionof10.1128/mSphere.00542-20en_US
dc.relation.journalmSphereen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0*
dc.sourcePMCen_US
dc.subjectApicomplexaen_US
dc.subjectToxoplasmaen_US
dc.subjectcell cycleen_US
dc.subjectchromatinen_US
dc.subjectdifferentiationen_US
dc.subjectparasitesen_US
dc.subjecttranscriptionen_US
dc.titleToxoplasma gondii AP2XII-2 Contributes to Proper Progression through S-Phase of the Cell Cycleen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
mSphere.00542-20.pdf
Size:
2.29 MB
Format:
Adobe Portable Document Format
Description:
Main article
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: