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Understanding the pathogenicity of Naegleria fowleri in association with N. fowleri antigen-1 (Nfa1)
Jong-Hyun Kim, Hae-Jin Sohn, Ho-Joon Shin, Stacy E. Walz, Suk-Yul Jung
Parasites Hosts Dis 2024;62(4):385-398.
Published online November 22, 2024
DOI: https://doi.org/10.3347/PHD.24025
Naegleria fowleri, a brain-eating amoeba, thrives in lakes and rivers with aquatic vegetation and causes primary amoebic meningoencephalitis (PAM) in humans. Most recently, it has become such a serious problem that N. fowleri was detected in tap water in Houston, USA. Several pathogenic factors are considered very important to destroy target cells in the brain. In particular, the food-cup where N. fowleri antigen-1 (Nfa1) is located, is strongly expressed in pseudopodia involved in the movement of N. fowleri, and is involved in phagocytosis by attaching to target cells. In this article, we reviewed the role of the Nfa1 protein and its associated pathogenicity. The nfa1 gene was cloned by cDNA library immunoscreening using infection serum and immune serum. Nfa1 protein is mainly distributed in pseudopodia important to movement and vacuoles. Moreover, heat shock protein 70, cathepsin-like proteare and Nf-actin are also associated with pseudopodia in which Nfa1 is localized. Interestingly, the amount of the nfa1 gene changed as N. fowleri trophozoites transformed into cysts. Polyclonal antiserum against Nfa1 showed a protective effect against cytotoxicity of approximately 19.7%. Nfa1-specific IgA antibodies prevent N. fowleri trophozoites from adhering to the nasal mucosa, delaying invasion. The nfa1-vaccinated mice showed significantly higher levels of Nfa1-specific antibody. The duration of anti-Nfa1 IgG in the vaccinated mice lasted 12 weeks, strongly suggesting that nfa1 is a significant pathogenic gene and that Nfa1 is a pathogenic protein. Several factors related to pseudopodia and locomotion have been linked to Nfa1. A clearer function of N. fowleri targeting nfa1 with other genes might enable target-based inhibition of N. fowleri pathogenicity.

Citations

Citations to this article as recorded by  Crossref logo
  • Computational exploration of natural inhibitors against toxin-associated proteins in Naegleria fowleri Karachi strain
    Rabia Faizan, Muhammad Naveed, Inmaculada Bellido Estevez, Nimra Hanif, Arooj Arshad, Tariq Aziz, Abdulhakeem S. Alamri, Walaa F. Alsanie, Majid Alhomrani
    Pathology - Research and Practice.2025; 274: 156184.     CrossRef
  • A review of the mechanism, diagnosis, and treatment of Naegleria fowleri infection
    Ling Dai, Xin-Ru Guo, Xu-Rui Chen, Ming-Hao Ma, Zi-Han Liu, Juan Lai, Jun Lu, Ming Feng, Xi-Xia Liu, Sheng-Hui Yang
    Frontiers in Microbiology.2025;[Epub]     CrossRef
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Original Articles
Interaction of Escherichia coli K1 and K5 with Acanthamoeba castellanii Trophozoites and Cysts
Abdul Matin, Suk-Yul Jung
Korean J Parasitol 2011;49(4):349-356.
Published online December 16, 2011
DOI: https://doi.org/10.3347/kjp.2011.49.4.349

The existence of symbiotic relationships between Acanthamoeba and a variety of bacteria is well-documented. However, the ability of Acanthamoeba interacting with host bacterial pathogens has gained particular attention. Here, to understand the interactions of Escherichia coli K1 and E. coli K5 strains with Acanthamoeba castellanii trophozoites and cysts, association assay, invasion assay, survival assay, and the measurement of bacterial numbers from cysts were performed, and nonpathogenic E. coli K12 was also applied. The association ratio of E. coli K1 with A. castellanii was 4.3 cfu per amoeba for 1 hr but E. coli K5 with A. castellanii was 1 cfu per amoeba for 1 hr. By invasion and survival assays, E. coli K5 was recovered less than E. coli K1 but still alive inside A. castellanii. E. coli K1 and K5 survived and multiplied intracellularly in A. castellanii. The survival assay was performed under a favourable condition for 22 hr and 43 hr with the encystment of A. castellanii. Under the favourable condition for the transformation of trophozoites into cysts, E. coli K5 multiplied significantly. Moreover, the pathogenic potential of E. coli K1 from A. castellanii cysts exhibited no changes as compared with E. coli K1 from A. castellanii trophozoites. E. coli K5 was multiplied in A. castellanii trophozoites and survived in A. castellanii cysts. Therefore, this study suggests that E. coli K5 can use A. castellanii as a reservoir host or a vector for the bacterial transmission.

Citations

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  • The impact of environmental factors on the transport and survival of pathogens in agricultural soils from karst areas of Yunnan province, China: Laboratory column simulated leaching experiments
    Zhuo Ning, Shuaiwei Wang, Caijuan Guo, Min Zhang
    Frontiers in Microbiology.2023;[Epub]     CrossRef
  • Interaction between Naegleria fowleri and pathogenic Escherichia coli by mannose and changes in N. fowleri protease
    Dae-Hyun Son, Eun-Jung Kim, Abdul Matin, Suk-Yul Jung
    Parasitology Research.2022; 121(6): 1805.     CrossRef
  • First report of successful Naegleria detection from environmental resources of some selected areas of Rawlakot, Azad Jammu and Kashmir, Pakistan
    Abida Akbar, Abdul Hameed, Abdulaziz S. Alouffi, Mashal M. Almutairi, Tania Tanveer, Abdul Matin
    Acta Protozoologica.2022; 60: 37.     CrossRef
  • A one health approach versus Acanthamoeba castellanii, a potential host for Morganella morganii
    Ruqaiyyah Siddiqui, Anania Boghossian, Noor Akbar, Naveed Ahmed Khan
    International Microbiology.2022; 25(4): 781.     CrossRef
  • Environmental Free-Living Amoebae Can Predate on Diverse Antibiotic-Resistant Human Pathogens
    Félix Bornier, Eline Zas, Damien Potheret, Maria-Halima Laaberki, Bénédicte Coupat-Goutaland, Xavier Charpentier, Christopher A. Elkins
    Applied and Environmental Microbiology.2021;[Epub]     CrossRef
  • Heat and chlorine resistance of a soil Acanthamoeba sp. cysts in water
    A.A. Gabriel, D.C. Panaligan
    Journal of Applied Microbiology.2020; 129(2): 453.     CrossRef
  • АКАНТАМЕБИ ЯК РЕЗЕРВУАР ПАТОГЕННИХ БАКТЕРІЙ ТА ВІРУСІВ
    A. P. Chobotar
    Інфекційні хвороби.2019; (2): 66.     CrossRef
  • АКАНТАМЕБИ ЯК РЕЗЕРВУАР ПАТОГЕННИХ БАКТЕРІЙ ТА ВІРУСІВ (огляд літератури)
    A. P. Chobotar
    Здобутки клінічної і експериментальної медицини.2019; (2): 12.     CrossRef
  • Environmental Free-Living Amoebae Isolated from Soil in Khon Kaen, Thailand, Antagonize Burkholderia pseudomallei
    Parumon Noinarin, Pisit Chareonsudjai, Pinich Wangsomnuk, Surasak Wongratanacheewin, Sorujsiri Chareonsudjai, William C. Nierman
    PLOS ONE.2016; 11(11): e0167355.     CrossRef
  • Current and Past Strategies for Bacterial Culture in Clinical Microbiology
    Jean-Christophe Lagier, Sophie Edouard, Isabelle Pagnier, Oleg Mediannikov, Michel Drancourt, Didier Raoult
    Clinical Microbiology Reviews.2015; 28(1): 208.     CrossRef
  • Protozoan Cysts Act as a Survival Niche and Protective Shelter for Foodborne Pathogenic Bacteria
    Ellen Lambrecht, Julie Baré, Natascha Chavatte, Wim Bert, Koen Sabbe, Kurt Houf, H. Goodrich-Blair
    Applied and Environmental Microbiology.2015; 81(16): 5604.     CrossRef
  • Encystment in Acanthamoeba castellanii: A review
    David Lloyd
    Experimental Parasitology.2014; 145: S20.     CrossRef
  • Isolation and molecular characterization of potentially pathogenic Acanthamoeba genotypes from diverse water resources including household drinking water from Khyber Pakhtunkhwa, Pakistan
    Tania Tanveer, Abdul Hameed, Ambreen Gul Muazzam, Suk-Yul Jung, Asma Gul, Abdul Matin
    Parasitology Research.2013; 112(8): 2925.     CrossRef
  • The Fate of Helicobacter pylori Phagocytized by Acanthamoeba polyphaga Demonstrated by Fluorescent In Situ Hybridization and Quantitative Polymerization Chain Reaction Tests
    Charlotte D. Smith, Nicholas J. Ashbolt
    Current Microbiology.2012; 65(6): 805.     CrossRef
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Influence of calcium ion on host cell invasion and intracellular replication by Toxoplasma gondii
Hyun-Ouk Song, Myoung-Hee Ahn, Jae-Sook Ryu, Duk-Young Min, Kyoung-Hwan Joo, Young-Ha Lee
Korean J Parasitol 2004;42(4):185-193.
Published online December 20, 2004
DOI: https://doi.org/10.3347/kjp.2004.42.4.185

Toxoplasma gondii is an obligate intracellular protozoan parasite, which invades a wide range of hosts including humans. The exact mechanisms involved in its invasion are not fully understood. This study focused on the roles of Ca2+ in host cell invasion and in T. gondii replication. We examined the invasion and replication of T. gondii pretreated with several calcium modulators, the conoid extrusion of tachyzoites. Calmodulin localization in T. gondii were observed using the immunogold method, and Ca2+ levels in tachyzoites by confocal microscopy. In light microscopic observation, tachyzoites co-treated with A23187 and EGTA showed that host cell invasion and intracellular replication were decreased. The invasion of tachyzoites was slightly inhibited by the Ca2+ channel blockers, bepridiland verapamil, and by the calmodulin antagonist, calmidazolium. We observed that calcium saline containing A23187 induced the extrusion of tachyzoite conoid. By immunoelectron microscopy, gold particles bound to anti-calmodulin or anti-actin mAb, were found to be localized on the anterior portion of tachyzoites. Remarkably reduced intracellular Ca2+ was observed in tachyzoites treated with BAPTA/AM by confocal microscopy. These results suggest that host cell invasion and the intracellular replication of T. gondii tachyzoites are inhibited by the calcium ionophore, A23187, and by the extracellular calcium chelator, EGTA.

Citations

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  • Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis
    Xianmei Wang, Kun Guo, Zhili Shan, Zhu Ying, Zifu Zhu, Shiman Yang, Na Yang, Qun Liu, Lifang Wang, Jing Liu
    Communications Biology.2025;[Epub]     CrossRef
  • Calreticulin (CALR) promotes ionophore-induced microneme secretion in Toxoplasma gondii
    Zhili Shan, Xingju Song, Xu Yang, Yangfei Xue, Yayun Wu, Xianmei Wang, Jing Liu, Qun Liu
    Parasitology Research.2024;[Epub]     CrossRef
  • Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration
    Hyunho Kim, Sung-Hee Hong, Hyo Eun Jeong, Sewoon Han, Jinchul Ahn, Jin-A. Kim, Ji-Hun Yang, Hyun Jeong Oh, Seok Chung, Sang-Eun Lee
    Scientific Reports.2022;[Epub]     CrossRef
  • Toxoplasma gondiiinfection and risk of attention-deficit hyperactivity disorder: a systematic review and meta-analysis
    Tooran Nayeri, Shahabeddin Sarvi, Mahmood Moosazadeh, Zahra Hosseininejad, Afsaneh Amouei, Ahmad Daryani
    Pathogens and Global Health.2020; 114(3): 126.     CrossRef
  • Effects of Toxoplasma gondii infection on the function and integrity of human cerebrovascular endothelial cells and the influence of verapamil treatment in vitro
    M.S.R. Harun, Victoria Marsh, Nashwa A. Elsaied, Kevin F. Webb, Hany M. Elsheikha
    Brain Research.2020; 1746: 147002.     CrossRef
  • Resistance towards monensin is proposed to be acquired in aToxoplasma gondiimodel by reduced invasion and egress activities, in addition to increased intracellular replication
    AHMED THABET, JOHANNES SCHMIDT, SVEN BAUMANN, WALTHER HONSCHA, MARTIN VON BERGEN, ARWID DAUGSCHIES, BERIT BANGOURA
    Parasitology.2018; 145(3): 313.     CrossRef
  • Anti-Toxoplasmosis Effect of the Herbal Extracts Plantago asiatica L.
    Sunhwa Hong, Okjin Kim
    Korean Journal of Plant Resources.2016; 29(1): 26.     CrossRef
  • Anti-Toxoplasmosis effects of herbal extracts against Toxoplasma Gondii
    Sunhwa Hong, Hyun-A Lee, Yung-Ho Chung, Tae-Wan Kim, Okjin Kim
    Korean Journal of Veterinary Service.2014; 37(2): 101.     CrossRef
  • Anti-Toxoplasmosis Effect of Meliae fructus Ethanol Extract
    Hak-Yong Lee, Okjin Kim
    Journal of Biomedical Research.2014; 15(4): 189.     CrossRef
  • Anti-Toxoplasmosis Effect of the Halophyte Suaeda maritime
    Sunhwa Hong, Hyun-A Lee, Yun-Seong Lee, Dong-Woo Kim, Jae-Hyeok Jeong, Tae-Wan Kim, Okjin Kim
    Korean Journal of Plant Resources.2014; 27(5): 415.     CrossRef
  • Anti-toxoplasmosis effect of Dictamnus dasycarpus extract against Toxoplasma Gondii
    Sunhwa Hong, Hyun-A Lee, Yun-seong Lee, Yung-Ho Chung, Okjin Kim
    Journal of Biomedical Research.2014; 15(1): 7.     CrossRef
  • Interplay of host–pathogen microvesicles and their role in infectious disease
    Jameel M. Inal, Ephraim A. Ansa-Addo, Sigrun Lange
    Biochemical Society Transactions.2013; 41(1): 258.     CrossRef
  • The effect of kinase, actin, myosin and dynamin inhibitors on host cell egress by Toxoplasma gondii
    Lucio Ayres Caldas, Sergio Henrique Seabra, Márcia Attias, Wanderley de Souza
    Parasitology International.2013; 62(5): 475.     CrossRef
  • Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders
    C. J. Carter
    Journal of Pathogens.2013; 2013: 1.     CrossRef
  • In vitro effects of aqueous extracts of Astragalus membranaceus and Scutellaria baicalensis GEORGI on Toxoplasma gondii
    Xiaoyan Yang, Bo Huang, Jianping Chen, Shiguang Huang, Huanqin Zheng, Zhao-Rong Lun, Jilong Shen, Yong Wang, Fangli Lu
    Parasitology Research.2012; 110(6): 2221.     CrossRef
  • Simple and efficient model systems of screening anti-Toxoplasmadrugsin vitro
    Chunmei Jin, Suk-Yul Jung, Sung Yeon Kim, Hyun-Ok Song, Hyun Park
    Expert Opinion on Drug Discovery.2012; 7(3): 195.     CrossRef
  • Identification of Putative Potassium Channel Homologues in Pathogenic Protozoa
    David L. Prole, Neil V. Marrion, Gordon Langsley
    PLoS ONE.2012; 7(2): e32264.     CrossRef
  • In vitro and experimental therapeutic studies of the calcium channel blocker bepridil: Detection of viable Leishmania (L.) chagasi by real-time PCR
    Juliana Q. Reimão, Fábio A. Colombo, Vera L. Pereira-Chioccola, André G. Tempone
    Experimental Parasitology.2011; 128(2): 111.     CrossRef
  • Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs
    Juliana Quero Reimão, André Gustavo Tempone
    Memórias do Instituto Oswaldo Cruz.2011; 106(8): 1032.     CrossRef
  • Microscopic analysis of calcium ionophore activated egress of Toxoplasma gondii from the host cell
    Lucio Ayres Caldas, Wanderley de Souza, Márcia Attias
    Veterinary Parasitology.2010; 167(1): 8.     CrossRef
  • Induction and regulation of conoid extrusion inToxoplasma gondii
    M. González Del Carmen, M. Mondragón, S. González, R. Mondragón
    Cellular Microbiology.2009; 11(6): 967.     CrossRef
  • THE IMPORTANCE OF TOXOPLASMA GONDII INFECTION IN DISEASES PRESENTING WITH HEADACHES. HEADACHES AND ASEPTIC MENINGITIS MAY BE MANIFESTATIONS OF THE JARISCH-HERXHEIMER REACTION
    JOSEPH PRANDOTA
    International Journal of Neuroscience.2009; 119(12): 2144.     CrossRef
  • Idiopatyczne nadciśnienie śródczaszkowe, guz rzekomy czaszki oraz aseptyczne zapalenie opon mogą być spowodowane reaktywacją latentnej toksoplazmozy mózgowej
    Józef Prandota
    Pediatria Polska.2009; 84(5): 453.     CrossRef
  • Characterization of a New Gene <italic>wx2</italic> in <italic>Toxoplasma gondii</italic>
    Xiang Wu, Qiong Zhang, Kui Tan, Ronghua Xie, Jiubo Fan, Hengping Shu, Shiping Wang
    Acta Biochimica et Biophysica Sinica.2007; 39(7): 475.     CrossRef
  • Laser scanning cytometer‐based assays for measuring host cell attachment and invasion by the human pathogen Toxoplasma gondii
    Jeffrey Mital, Janet Schwarz, Douglas J. Taatjes, Gary E. Ward
    Cytometry Part A.2006; 69A(1): 13.     CrossRef
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Effects of specific monoclonal antibodies to dense granular proteins on the invasion of Toxoplasma gondii in vitro and in vivo
Dong Yeob Cha, In Kwan Song, Gye Sung Lee, Ok-Sun Hwang, Hyung-Jun Noh, Seung-Dong Yeo, Dae-Whan Shin, Young-Ha Lee
Korean J Parasitol 2001;39(3):233-240.
Published online September 30, 2001
DOI: https://doi.org/10.3347/kjp.2001.39.3.233

Although some reports have been published on the protective effect of antibodies to Toxoplasma gondii surface membrane proteins, few address the inhibitory activity of antibodies to dense granular proteins (GRA proteins). Therefore, we performed a series of experiments to evaluate the inhibitory effects of monoclonal antibodies (mAbs) to GRA proteins (GRA2, 28 kDa; GRA6, 32 kDa) and surface membrane protein (SAG1, 30 kDa) on the invasion of T. gondii tachyzoites. Passive immunization of mice with one of three mAbs following challenge with a lethal dose of tachyzoites significantly increased survival compared with results for mice treated with control ascites. The survival times of mice challenged with tachyzoites pretreated with anti-GRA6 or anti-SAG1 mAb were significantly increased. Mice that received tachyzoites pretreated with both mAb and complement had longer survival times than those that received tachyzoites pretreated with mAb alone. Invasion of tachyzoites into fibroblasts and macrophages was significantly inhibited in the anti-GRA2, anti-GRA6 or anti-SAG1 mAb pretreated group. Pretreatment with mAb and complement inhibited invasion of tachyzoites in both fibroblasts and macrophages. These results suggest that specific antibodies to dense-granule molecules may be useful for controlling infection with T. gondii.

Citations

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  • Different kinetics of humoral response against individual antigens in the ovine model of Toxoplasma gondii infection and its pathological association
    Paula Formigo, Ignacio Gual, Germán J. Cantón, Luisa F. Mendoza Morales, Emiliano Sosa, Agustina Soto Cabrera, Valeria Scioli, Claudia Morsella, Valeria A. Sander, Dadin P. Moore, Sergio O. Angel, Lucía M. Campero, Marina Clemente
    Frontiers in Immunology.2025;[Epub]     CrossRef
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    Mohammad Mahdi Jafari, Zahra Azimzadeh Tabrizi, Mohammad Saaid Dayer, Nazanin Atieh Kazemi-Sefat, Mahshid Mohtashamifard, Rahimeh Mohseni, Atefeh Bagheri, Saeed Bahadory, Amir Karimipour-Saryazdi, Fatemeh Ghaffarifar
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    Xiaowei Tian, Hanqi Sun, Meng Wang, Guangmin Wan, Tong Xie, Xuefang Mei, Zhenchao Zhang, Xiangrui Li, Shuai Wang
    Frontiers in Veterinary Science.2022;[Epub]     CrossRef
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    International Journal for Parasitology.2021; 51(2-3): 95.     CrossRef
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  • Evaluation of protective effect of recombinant dense granule antigens GRA2 and GRA6 formulated in monophosphoryl lipid A (MPL) adjuvant against Toxoplasma chronic infection in mice
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    Vaccine.2007; 25(21): 4301.     CrossRef
  • 9,184 View
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  • Crossref