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101. CORR Insights®: Débridement and Reconstruction Improve Postoperative Sagittal Alignment in Kyphotic Cervical Spinal Tuberculosis

Author

Zeeshan Mohammad Sardar

Subjects
030222 orthopedics, medicine.medical_specialty, Tuberculosis, Sports medicine, business.industry, medicine.medical_treatment, General Medicine, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Debridement (dental), Orthopedic surgery, medicine, Sagittal alignment, Orthopedics and Sports Medicine, business, 030217 neurology & neurosurgery
Published
2017

102. Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation

Author

Zeeshan, Mohammad, primary, Pandey, Rajan, additional, Ferguson, David J.P., additional, Tromer, Eelco C., additional, Markus, Robert, additional, Abel, Steven, additional, Brady, Declan, additional, Daniel, Emilie, additional, Limenitakis, Rebecca, additional, Bottrill, Andrew R., additional, Le Roch, Karine G., additional, Holder, Anthony A., additional, Waller, Ross F., additional, Guttery, David S., additional, and Tewari, Rita, additional

Published
2019
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105. Is non-traditional therapy for multiple sclerosis overwhelming in Saudi Arabia

Author

Shariff, Erum M., primary, Al-Shammrani, Foziah J., additional, Nazish, Saima, additional, Zafar, Azra S., additional, Shahid, Rizwana M., additional, Khuda, Inam E., additional, Zeeshan, Mohammad A., additional, Alabdali, Majed A., additional, Al-Bakr, Aishah I., additional, Aljaafari, Danah T., additional, Balharith, Ibtesam O., additional, Alahmed, Ali A., additional, Alsalman, Sadiq A., additional, Almajed, Alaa M., additional, and Alkhamis, Fahd A., additional

Published
2019
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106. Kinesin-8B controls basal body function and flagellum formation and is key to malaria parasite transmission

Author

Zeeshan, Mohammad, primary, Ferguson, David J. P., additional, Abel, Steven, additional, Burrrell, Alana, additional, Rea, Edward, additional, Brady, Declan, additional, Daniel, Emilie, additional, Delves, Michael, additional, Vaughan, Sue, additional, Holder, Anthony A., additional, Le Roch, Karine G., additional, Moores, Carolyn A., additional, and Tewari, Rita, additional

Published
2019
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107. Plasmodium condensin core subunits (SMC2/SMC4) mediate atypical mitosis and are essential for parasite proliferation and transmission

Author

Pandey, Rajan, primary, Abel, Steven, additional, Boucher, Matthew, additional, Wall, Richard J., additional, Zeeshan, Mohammad, additional, Rea, Edward, additional, Freville, Aline, additional, Lu, Xueqing Maggie, additional, Brady, Declan, additional, Daniel, Emilie, additional, Stanway, Rebecca R., additional, Wheatley, Sally, additional, Batugedara, Gayani, additional, Hollin, Thomas, additional, Bottrill, Andrew R., additional, Gupta, Dinesh, additional, Holder, Anthony A., additional, Le Roch, Karine G., additional, and Tewari, Rita, additional

Published
2019
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108. Plasmodium Kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Author

Zeeshan, Mohammad, primary, Shilliday, Fiona, additional, Liu, Tianyang, additional, Abel, Steven, additional, Mourier, Tobias, additional, Ferguson, David J. P., additional, Rea, Edward, additional, Stanway, Rebecca R., additional, Roques, Magali, additional, Williams, Desiree, additional, Daniel, Emilie, additional, Brady, Declan, additional, Roberts, Anthony J., additional, Holder, Anthony A., additional, Pain, Arnab, additional, Le Roch, Karine G., additional, Moores, Carolyn A., additional, and Tewari, Rita, additional

Published
2019
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112. Evaluation of immune response to Hepatitis B vaccine in health care workers at a tertiary care hospital in Pakistan: an observational prospective study

Author

Farooqui Saadia Z, Ali Ailia, Ali Anita, Jabeen Kauser, Zeeshan Mohammad, Mehraj Vikram, and Zafar Afia

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Seroconversion rates reported after Hepatitis B virus (HBV) vaccination globally ranges from 85–90%. Health care workers (HCWs) are at high risk of acquiring HBV and non responders' rates after HBV vaccination were not reported previously in Pakistani HCWs. Therefore we evaluated immune response to HBV vaccine in HCWs at a tertiary care hospital in Karachi, Pakistan. Methods Descriptive observational study conducted at Aga Khan University from April 2003 to July 2004. Newly HBV vaccinated HCWs were evaluated for immune response by measuring serum Hepatitis B surface antibody (HBsAb) levels, 6 weeks post vaccination. Results Initially 666 employees were included in the study. 14 participants were excluded due to incomplete records. 271 (41%) participants were females and 381(59%) were males. Majority of the participants were young (50 years of age. Male non responders were more frequent (18%) than female (8%). Conclusion Seroconversion rate after HBV vaccination in Pakistani HCWs was similar to that reported in western and neighboring population. HCWs with reduced immune response to HBV vaccine in a high disease prevalent population are at great risk. Therefore, it is crucial to check post vaccination HBsAb in all HCWs. This strategy will ensure safety at work by reducing nosocomial transmission and will have a cost effective impact at an individual as well as at national level, which is very much desired in a resource limited country.

Published
2007
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113. An Efficient Recovery of Chromium From Tanning Liquor waste and its Reutilization for the Production of Quality Leather

Author

Zehra, Beena, Nawaz, Hafiz Rub, Solangi, Barkat Ali, Nadeem, Uzma, Ayaz, Tahira, Zeeshan, Mohammad, Zehra, Beena, Nawaz, Hafiz Rub, Solangi, Barkat Ali, Nadeem, Uzma, Ayaz, Tahira, and Zeeshan, Mohammad

Abstract

The conventional methods for the treatment of tannery effluents are highly expensive due to the presence of large amount of chemicals used in the processing and their environmental toxicity. In this study, chromium has been recovered from tanning waste liquor which is discarded usually in the open streams. This tanning liquor has been treated with different concentrations of alkalies such as sodium hydroxide (NaOH), ferric chloride (FeCl3) and magnesium oxide (MgO) to recover chromium using the precipitation method. The precipitation of chromium at controlled range of pH by MgO yielded the well concentrated sludge resulting the total dissolved solids in low quantity in the supernatant when compared with the other two treatments (NaOH and FeCl3). The prepared chromium sulphate liquors from recovered chrome cake has been employed at similar conditions parallel to fresh basic chromium sulphate to determine the effects on quality of leather. The resulted leathers showed almost very good properties e.g. shrinkage, tear strength, tensile strength, bursting strength, fullness, grain smoothness, etc.

Published
2018

114. Additional file 1: of Readiness for antimicrobial resistance (AMR) surveillance in Pakistan; a model for laboratory strengthening

Author

Saeed, Dania, Rumina Hasan, Mahwish Naim, Zafar, Afia, Erum Khan, Kausar Jabeen, Irfan, Seema, Ahmed, Imran, Zeeshan, Mohammad, Zabin Wajidali, Joveria Farooqi, Shakoor, Sadia, Chagla, Abdul, and Rao, Jason

Abstract

Self-administered questionnaire used to assess laboratory capacity for AMR testing. Presents the self-administered questionnaire used for evaluating laboratory capacity. (DOCX 44Â kb)

Published
2017
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115. Additional file 3: of Readiness for antimicrobial resistance (AMR) surveillance in Pakistan; a model for laboratory strengthening

Author

Saeed, Dania, Rumina Hasan, Mahwish Naim, Zafar, Afia, Erum Khan, Kausar Jabeen, Irfan, Seema, Ahmed, Imran, Zeeshan, Mohammad, Zabin Wajidali, Joveria Farooqi, Shakoor, Sadia, Chagla, Abdul, and Rao, Jason

Abstract

Questionnaire to evaluate impact of knowledge based intervention on laboratory performance during study period. Presents questionnaire used for evaluating impact of knowledge based intervention on laboratory performance during the study period. (DOCX 12Â kb)

Published
2017
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116. Additional file 2: of Readiness for antimicrobial resistance (AMR) surveillance in Pakistan; a model for laboratory strengthening

Author

Saeed, Dania, Rumina Hasan, Mahwish Naim, Zafar, Afia, Erum Khan, Kausar Jabeen, Irfan, Seema, Ahmed, Imran, Zeeshan, Mohammad, Zabin Wajidali, Joveria Farooqi, Shakoor, Sadia, Chagla, Abdul, and Rao, Jason

Abstract

Scoring method used including percentage scores for each question in a given category. Total scores and percentage scores for each category of laboratory capacity for both public and private sector are also presented. Presents the scores including total percentage of public and private sector in each category as well as the individual scores in the different components that constituted a particular category. (DOCX 25Â kb)

Published
2017
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120. Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum

Author

Prakash, Prem, primary, Zeeshan, Mohammad, additional, Saini, Ekta, additional, Muneer, Azhar, additional, Khurana, Sachin, additional, Kumar Chourasia, Bishwanath, additional, Deshmukh, Arunaditya, additional, Kaur, Inderjeet, additional, Dabral, Surabhi, additional, Singh, Niharika, additional, Anam, Zille, additional, Chaurasiya, Ayushi, additional, Kaushik, Shikha, additional, Dahiya, Pradeep, additional, Kalamuddin, Md., additional, Kumar Thakur, Jitendra, additional, Mohmmed, Asif, additional, Ranganathan, Anand, additional, and Malhotra, Pawan, additional

Published
2017
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121. Photosensitized INA-Labelled protein 1 (PhIL1) is novel component of the inner membrane complex and is required for Plasmodium parasite development

Author

Saini, Ekta, primary, Zeeshan, Mohammad, additional, Brady, Declan, additional, Pandey, Rajan, additional, Kaiser, Gesine, additional, Koreny, Ludek, additional, Kumar, Pradeep, additional, Thakur, Vandana, additional, Tatiya, Shreyansh, additional, Katris, Nicholas J., additional, Limenitakis, Rebecca Stanway, additional, Kaur, Inderjeet, additional, Green, Judith L., additional, Bottrill, Andrew R., additional, Guttery, David S., additional, Waller, Ross F., additional, Heussler, Volker, additional, Holder, Anthony A., additional, Mohmmed, Asif, additional, Malhotra, Pawan, additional, and Tewari, Rita, additional

Published
2017
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122. Readiness for antimicrobial resistance (AMR) surveillance in Pakistan; a model for laboratory strengthening

Author

Saeed, Dania Khalid, primary, Hasan, Rumina, additional, Naim, Mahwish, additional, Zafar, Afia, additional, Khan, Erum, additional, Jabeen, Kausar, additional, Irfan, Seema, additional, Ahmed, Imran, additional, Zeeshan, Mohammad, additional, Wajidali, Zabin, additional, Farooqi, Joveria, additional, Shakoor, Sadia, additional, Chagla, Abdul, additional, and Rao, Jason, additional

Published
2017
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123. Primary hyperoxaluria in populations of Pakistan origin: results from a literature review and two major registries

Author

Talati, Jamsheer Jehangir, primary, Hulton, Sally-Anne, additional, Garrelfs, Sander F., additional, Aziz, Wajahat, additional, Rao, Shoaib, additional, Memon, Amanullah, additional, Nazir, Zafar, additional, Biyabani, Raziuddin, additional, Qazi, Saqib, additional, Azam, Iqbal, additional, Khan, Aysha Habib, additional, Ahmed, Jamil, additional, Jafri, Lena, additional, and Zeeshan, Mohammad, additional

Published
2017
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129. Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum.

Author

Zeeshan, Mohammad, Saini, Ekta, Muneer, Azhar, Khurana, Sachin, Chourasia, Bishwanath Kumar, Deshmukh, Arunaditya, Kaur, Inderjeet, Dabral, Surabhi, Kalamuddin, Md., Mohmmed, Asif, Malhotra, Pawan, Prakash, Prem, Singh, Niharika, Ranganathan, Anand, Anam, Zille, Chaurasiya, Ayushi, Kaushik, Shikha, Dahiya, Pradeep, and Thakur, Jitendra Kumar

Subjects
PLASMODIUM falciparum, CYCLOPHILINS, ERYTHROCYTES, MEROZOITES, PROTEIN-protein interactions
Abstract

Invasion of human erythrocytes by Plasmodium falciparum merozoites involves multiple interactions between host receptors and their merozoite ligands. Here we report human Cyclophilin B as a receptor for PfRhopH3 during merozoite invasion. Localization and binding studies show that Cyclophilin B is present on the erythrocytes and binds strongly to merozoites. We demonstrate that PfRhopH3 binds to the RBCs and their treatment with Cyclosporin A prevents merozoite invasion. We also show a multi-protein complex involving Cyclophilin B and Basigin, as well as PfRhopH3 and PfRh5 that aids the invasion. Furthermore, we report identification of a de novo peptide CDP3 that binds Cyclophilin B and blocks invasion by up to 80%. Collectively, our data provide evidence of compounded interactions between host receptors and merozoite surface proteins and paves the way for developing peptide and small-molecules that inhibit the protein−protein interactions, individually or in toto, leading to abrogation of the invasion process. [ABSTRACT FROM AUTHOR]

Published
2017
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136. Genetic Variation in the Plasmodium falciparum Circumsporozoite Protein in India and Its Relevance to RTS,S Malaria Vaccine

Author

Zeeshan, Mohammad, primary, Alam, Mohammad Tauqeer, additional, Vinayak, Sumiti, additional, Bora, Hema, additional, Tyagi, Rupesh Kumar, additional, Alam, Mohd Shoeb, additional, Choudhary, Vandana, additional, Mittra, Pooja, additional, Lumb, Vanshika, additional, Bharti, Praveen Kumar, additional, Udhayakumar, Venkatachalam, additional, Singh, Neeru, additional, Jain, Vidhan, additional, Singh, Pushpendra Pal, additional, and Sharma, Yagya Dutta, additional

Published
2012
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137. Proteomic Identification and Analysis of Arginine-Methylated Proteins of Plasmodium falciparumat Asexual Blood Stages

Author

Zeeshan, Mohammad, Kaur, Inderjeet, Joy, Joseph, Saini, Ekta, Paul, Gourab, Kaushik, Abhinav, Dabral, Surbhi, Mohmmed, Asif, Gupta, Dinesh, and Malhotra, Pawan

Abstract

Plasmodium falciparumundergoes a tightly regulated developmental process in human erythrocytes, and recent studies suggest an important regulatory role of post-translational modifications (PTMs). As compared with Plasmodiumphosphoproteome, little is known about other PTMs in the parasite. In the present study, we performed a global analysis of asexual blood stages of Plasmodium falciparumto identify arginine-methylated proteins. Using two different methyl arginine-specific antibodies, we immunoprecipitated the arginine-methylated proteins from the stage-specific parasite lysates and identified 843 putative arginine-methylated proteins by LC–MS/MS. Motif analysis of the protein sequences unveiled that the methylation sites are associated with the previously known methylation motifs such as GRx/RGx, RxG, GxxR, or WxxxR. We identified Plasmodiumhomologues of known arginine-methylated proteins in trypanosomes, yeast, and human. Hydrophilic interaction liquid chromatography (HILIC) was performed on the immunoprecipitates from the trophozoite stage to enrich arginine-methylated peptides. Mass spectrometry analysis of immunoprecipitated and HILIC fractions identified 55 arginine-methylated peptides having 62 methylated arginine sites. Functional classification revealed that the arginine-methylated proteins are involved in RNA metabolism, protein synthesis, intracellular protein trafficking, proteolysis, protein folding, chromatin organization, hemoglobin metabolic process, and several other functions. Summarily, the findings suggest that protein methylation of arginine residues is a widespread phenomenon in Plasmodium, and the PTM may play an important regulatory role in a diverse set of biological pathways, including host–pathogen interactions.

Published
2017
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141. CORR Insights®: Débridement and Reconstruction Improve Postoperative Sagittal Alignment in Kyphotic Cervical Spinal Tuberculosis.

Author

Sardar, Zeeshan and Sardar, Zeeshan Mohammad

Subjects
*SPINAL tuberculosis, *TUBERCULOSIS treatment, *DEBRIDEMENT, *CERVICAL vertebrae, *KYPHOSIS, *POSTOPERATIVE period, *SPINAL fusion, *TREATMENT effectiveness, *SPONDYLOSIS, *SURGERY
Abstract

The article discusses the diagnosis and treatment of patients affected with cervical spinal tuberculosis, with emphasis on the surgical approach for debridement and stabilization.

Published
2017
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142. CD4+T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivaxTryptophan-Rich Antigens

Author

Zeeshan, Mohammad, Tyagi, Kriti, and Sharma, Yagya D.

Abstract

ABSTRACTTryptophan-rich proteins play important biological functions for the Plasmodiumparasite. Plasmodium vivaxcontains remarkably large numbers of such proteins belonging to the “Pv-fam-a” family that need to be characterized. Earlier, we reported the presence of memory T cells and naturally acquired antibodies against 15 of these proteins in P. vivaxmalaria-exposed individuals (M. Zeeshan, H. Bora, and Y. D. Sharma, J Infect Dis 207:175–185, 2013, http://dx.doi.org/10.1093/infdis/jis650). Here, we sought to characterize and ascertain the cross talk between effector responses of T and B cells in malarial patients against all Pv-fam-a family proteins. Therefore, we expressed the remaining 21 of these proteins in Escherichia coliand studied the humoral and cellular immune responses based on the same parameters used in our previous study. Naturally acquired IgG antibodies were detected against all 21 antigens in P. vivaxpatient sera (37.7 to 94.4% seropositivity). These antigens were able to activate the lymphocytes of P. vivax-exposed individuals, and the activated CD4+T lymphocytes produced higher levels of Th1 (interleukin-2 [IL-2] and gamma interferon [IFN-γ]) and Th2 (IL-4 and IL-10) cytokines than the healthy controls, but the response was Th2 biased. The combined results of present and previous studies seem to suggest a striking link between induction of the CD4+T cell response and naturally acquired antibodies against all 36 proteins of the Pv-fam-a family, the majority of them having conserved sequences in the parasite population. Further work is required to utilize this information to develop immunotherapeutic treatments for this disease.

Published
2015
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143. Evaluation of immune response to Hepatitis B vaccine in healthcare workers at a tertiary care hospital in Pakistan: an observationalprospective study.

Author

Zeeshan, Mohammad, Jabeen, Kauser, Ali, Anita Nausheen Akbar, Ali, Ailia Wilayat, Farooqui, Saadia Z., Mehraj, Vikram, and Zafar, Afia

Subjects
*IMMUNE response, *HEPATITIS B vaccines, *MEDICAL personnel, *PREVENTION of communicable diseases
Abstract

Background: Seroconversion rates reported after Hepatitis B virus (HBV) vaccination globally ranges from 85-90%. Health care workers (HCWs) are at high risk of acquiring HBV and non responders' rates after HBV vaccination were not reported previously in Pakistani HCWs. Therefore we evaluated immune response to HBV vaccine in HCWs at a tertiary care hospital in Karachi, Pakistan. Methods: Descriptive observational study conducted at Aga Khan University from April 2003 to July 2004. Newly HBV vaccinated HCWs were evaluated for immune response by measuring serum Hepatitis B surface antibody (HBsAb) levels, 6 weeks post vaccination. Results: Initially 666 employees were included in the study. 14 participants were excluded due to incomplete records. 271 (41%) participants were females and 381(59%) were males. Majority of the participants were young (<25-39 years old), regardless of gender. Out of 652 HCWs, 90 (14%) remained seronegative after six weeks of post vaccination. The percentage of non responders increased gradually from 9% in participants of <25, 13% in 25-34, 26% in 35-49, and 63% in >50 years of age. Male non responders were more frequent (18%) than female (8%). Conclusion: Seroconversion rate after HBV vaccination in Pakistani HCWs was similar to that reported in western and neighboring population. HCWs with reduced immune response to HBV vaccine in a high disease prevalent population are at great risk. Therefore, it is crucial to check post vaccination HBsAb in all HCWs. This strategy will ensure safety at work by reducing nosocomial transmission and will have a cost effective impact at an individual as well as at national level, which is very much desired in a resource limited country. [ABSTRACT FROM AUTHOR]

Published
2007
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144. Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation.

Author

Zeeshan, Mohammad, Pandey, Rajan, Ferguson, David J. P., Tromer, Eelco C., Markus, Robert, Abel, Steven, Brady, Declan, Daniel, Emilie, Limenitakis, Rebecca, Bottrill, Andrew R., Le Roch, Karine G., Holder, Anthony A., Waller, Ross F., Guttery, David S., and Tewari, Rita

Subjects
*CHROMOSOME segregation, *MITOSIS, *MICROTUBULES, *NUCLEAR membranes, *PLASMODIUM, *SPINDLE apparatus, *PLASMODIUM berghei
Abstract

Eukaryotic cell proliferation requires chromosome replication and precise segregation to ensure daughter cells have identical genomic copies. Species of the genus Plasmodium, the causative agents of malaria, display remarkable aspects of nuclear division throughout their life cycle to meet some peculiar and unique challenges to DNA replication and chromosome segregation. The parasite undergoes atypical endomitosis and endoreduplication with an intact nuclear membrane and intranuclear mitotic spindle. To understand these diverse modes of Plasmodium cell division, we have studied the behaviour and composition of the outer kinetochore NDC80 complex, a key part of the mitotic apparatus that attaches the centromere of chromosomes to microtubules of the mitotic spindle. Using NDC80-GFP live-cell imaging in Plasmodium berghei, we observe dynamic spatiotemporal changes during proliferation, including highly unusual kinetochore arrangements during sexual stages. We identify a very divergent candidate for the SPC24 subunit of the NDC80 complex, previously thought to be missing in Plasmodium, which completes a canonical, albeit unusual, NDC80 complex structure. Altogether, our studies reveal the kinetochore to be an ideal tool to investigate the non-canonical modes of chromosome segregation and cell division in Plasmodium. [ABSTRACT FROM AUTHOR]

Published
2021
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147. PlasmodiumCondensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission

Author

Pandey, Rajan, Abel, Steven, Boucher, Matthew, Wall, Richard J., Zeeshan, Mohammad, Rea, Edward, Freville, Aline, Lu, Xueqing Maggie, Brady, Declan, Daniel, Emilie, Stanway, Rebecca R., Wheatley, Sally, Batugedara, Gayani, Hollin, Thomas, Bottrill, Andrew R., Gupta, Dinesh, Holder, Anthony A., Le Roch, Karine G., and Tewari, Rita

Abstract

Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodiumspp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2and smc4gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle.

Published
2020
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149. Molecular characterization of the conoid complex in Toxoplasma reveals its conservation in all apicomplexans, including Plasmodium species

Author

Koreny, Ludek, Zeeshan, Mohammad, Barylyuk, Konstantin, Tromer, Eelco C., Van Hooff, Jolien J. E., Brady, Declan, Ke, Huiling, Chelaghma, Sara, Ferguson, David J. P., Eme, Laura, Tewari, Rita, and Waller, Ross F.

Subjects
Biology and life sciences, parasitic diseases, 3. Good health, Research Article
Abstract

The apical complex is the instrument of invasion used by apicomplexan parasites, and the conoid is a conspicuous feature of this apparatus found throughout this phylum. The conoid, however, is believed to be heavily reduced or missing from Plasmodium species and other members of the class Aconoidasida. Relatively few conoid proteins have previously been identified, making it difficult to address how conserved this feature is throughout the phylum, and whether it is genuinely missing from some major groups. Moreover, parasites such as Plasmodium species cycle through 3 invasive forms, and there is the possibility of differential presence of the conoid between these stages. We have applied spatial proteomics and high-resolution microscopy to develop a more complete molecular inventory and understanding of the organisation of conoid-associated proteins in the model apicomplexan Toxoplasma gondii. These data revealed molecular conservation of all conoid substructures throughout Apicomplexa, including Plasmodium, and even in allied Myzozoa such as Chromera and dinoflagellates. We reporter-tagged and observed the expression and location of several conoid complex proteins in the malaria model P. berghei and revealed equivalent structures in all of its zoite forms, as well as evidence of molecular differentiation between blood-stage merozoites and the ookinetes and sporozoites of the mosquito vector. Collectively, we show that the conoid is a conserved apicomplexan element at the heart of the invasion mechanisms of these highly successful and often devastating parasites.

150. Plasmodium kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Author

Zeeshan, Mohammad, Shilliday, Fiona, Tianyang Liu, Abel, Steven, Mourier, Tobias, Ferguson, David JP, Rea, Edward, Stanway, Rebecca R, Roques, Magali, Williams, Desiree, Daniel, Emilie, Brady, Declan, Roberts, Anthony J, Holder, Anthony A, Arnab Pain, Roch, Karine G Le, Moores, Carolyn A, and Tewari, Rita

Subjects
Model organisms, parasitic diseases, Infectious Disease, macromolecular substances, Cell Biology, Biochemistry & Proteomics, 3. Good health
Abstract

Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the plus ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics in the different proliferative stages are not well understood. Genome-wide shared orthology analysis of Plasmodium spp. revealed the presence of two kinesin-8 motor proteins, kinesin-8X and kinesin-8B. Here we studied the biochemical properties of kinesin-8X and its role in parasite proliferation. In vitro, kinesin-8X has motility and depolymerization activities like other kinesin-8 motors. To understand the role of Plasmodium kinesin-8X in cell division, we used fluorescence-tagging and live cell imaging to define its location, and gene targeting to analyse its function, during all proliferative stages of the rodent malaria parasite P. berghei life cycle. The results revealed a spatio-temporal involvement of kinesin-8X in spindle dynamics and an association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the kinesin-8X gene revealed a defect in oocyst development, confirmed by ultrastructural studies, suggesting that this protein is required for oocyst development and sporogony. Transcriptome analysis of Δkinesin-8X gametocytes revealed modulated expression of genes involved mainly in microtubule-based processes, chromosome organisation and the regulation of gene expression, supporting a role for kinesin-8X in cell division. Kinesin-8X is thus required for parasite proliferation within the mosquito and for transmission to the vertebrate host.

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