Current topics in membranes最新文献

Toxoplasma gondii is one of the most successful protozoan parasites in the world, chronically infecting around 25-30 % of the human population. As a member of the phylum Apicomplexa, Toxoplasma has unique cellular structures, the best known being the apical complex and, no less notable, a trilaminar pellicle structure formed by the plasma membrane on top of a set of flattened membranous sacs (alveoli) called inner membrane complex. As an obligated intracellular pathogen, T. gondii pellicle contains an arsenal of proteins involved in host cell recognition and adhesion, which are crucial for cell invasion. Besides, the pellicle also houses molecular motor machinery that drives the parasite gliding motility. Thus, this chapter will dissect the structure of the pellicle and will also address its main molecular components.

Extracellular vesicles (EVs) are considered as cornerstones of cell-cell communication. EVs are bio-membrane naturally occurring vesicles generated by both eukaryotic and prokaryotic cells to transfer myriad cargo between close and distant cells to modulate them genetically or at functional levels. Recently, attention has been attracted towards the use of EVs derived from different sources like mammalian, bacterial and plant cells for drug delivery and diagnostic applications. Although all types of EVs vary in their compositions and biogenesis, they have similar features which made them desirable and novel theranostics. Today, breast cancer is a challenging disease to humans around the world, hence, accurate and timely diagnosis and selecting the most appropriate therapeutic plan are pivotal steps forward reducing mortality. In this chapter, we have focused on unique features of EVs to be employed in the diagnosis of breast cancer because of the presence of the data inside the EVs which are related to their origin cells. Also, imaging agents can be enclosed by EVs, providing a high sensitive and reproducible imaging technique. Moreover, EVs are recruited as novel strategies to reach chemotherapeutic molecules to breast cancer in targeted drug delivery. Lastly, by discussing the pros and cons of various types of EVs as theranostics, we shed a light on the role of EVs in breast cancer and underlined the challenges that have to be overcome.

The genome of the Trypanosoma cruzi parasite exhibits a significant expansion of genes that encode surface proteins in comparison to other trypanosomatids, specifically Trypanosoma brucei and Leishmania. Many of these proteins are encoded by large and diverse gene families, predominantly expressed on the surface of the trypomastigote stage, which infects a variety of mammalian host cells and circulates in the bloodstream, disseminating the infection throughout the organism. While some members of these families may be found at the telomeres, the majority are clustered in long arrays of genes within the chromosomes. These regions, referred to as disruptive compartments, undergo more rapid evolution than the core compartments, which are enriched in conserved and housekeeping protein coding-genes common to other trypanosomatids. In this chapter, we will discuss the features and process underlying the variability of the largest T. cruzi gene families and its implications for parasite survival.

Extracellular vesicles (EVs) play a central role in the host-parasite interplay during Trypanosoma cruzi infection and the progression of Chagas disease. Released by both parasite and host cells, EVs modulate immune responses, promote parasite persistence, and sustain inflammation through their diverse cargo, including proteins, lipids, and RNAs. Parasite-derived components such as MASP, trans-sialidases, and TESA, as well as small non-coding RNAs, have been identified within EVs and are increasingly explored as diagnostic and prognostic biomarkers. Their stability in biological fluids and parasite-specific content offer advantages over conventional serology, particularly for chronic disease stages. Experimental models further demonstrate that EVs influence cytokine profiles, enhance parasitemia, and affect complement resistance, highlighting their dual role in immune modulation and disease outcome. Beyond pathogenesis, EVs hold promise as antigen sources for serological assays, as non-invasive biomarkers for disease monitoring, and as innovative platforms for vaccine and therapeutic development. Together, these findings underscore the translational potential of EVs in advancing diagnosis, prognosis, and treatment strategies for Chagas disease.

The initial interaction between host cells and Leishmania infective rforms is dependent on surface proteins from both organisms. Membrane proteins are fundamental molecules that perform a variety of functions, including recognition, adhesion, and host cell penetration, as well as nutrient and enzyme transport and cell signaling. Several Leishmania plasma membrane proteins play critical roles in host interaction, parasite survival, and virulence during the early stages of infection. Among them, the most prominent is GP63, which confers resistance to complement-mediated lysis and induces macrophage phagocytosis. Another important surface protein, prohibitin, has a role in macrophage infection and has demonstrated the ability to generate a humoral response in human patients, making it a potential diagnostic marker. Furthermore, prohibitin is considered a promising target for vaccination against L. infantum. The kinetoplastid membrane protein 11 (KMP11) has also been identified as a potential B- and T-cell immunogen during infection. The analysis of the membrane proteome profile of Leishmania promastigotes could offer a more comprehensive understanding of host-parasite interactions and Leishmania biology. Despite membrane proteins constituting 20-30 % of the proteome in most organisms, there are relatively few proteomic studies on Leishmania parasites that focus on membrane-associated proteins, even though these proteins are potential drug targets. This review provides a survey of the current knowledge regarding the composition of plasma membrane focusing, in alphabetical order, on those proteins that are best characterized in terms of functionality in Leishmania.

Extracellular vesicles (EVs) are emerging as key players in the pathogenesis of malaria and toxoplasmosis, two significant infectious diseases caused by Apicomplexa parasites. This chapter investigates the multifaceted roles of EVs in the progression of these diseases, emphasizing their involvement in immune modulation, hostparasite interactions, and the regulation of disease severity. In malaria, EVs derived from infected red blood cells, platelets, and endothelial cells contribute to disease symptoms, immune response modulation, and parasite survival and have potential as biomarkers and tools for vaccine development. Similarly, in toxoplasmosis, EVs influence the modulation of immune responses and disease progression, presenting distinct profiles depending on the Toxoplasma gondii strain. Notably, EVs from both parasites contain immunogenic proteins that can be used in vaccine development, with promising results in preclinical studies. The role of EVs in these parasitic infections highlights their potential as therapeutic targets and diagnostic tools, providing new opportunities for the prevention and treatment of malaria and toxoplasmosis.

The development of vaccines to prevent diseases caused by parasites is urgent. Current treatments are highly toxic and ineffective. In addition, these diseases are more prevalent in vulnerable populations and can be fatal in children and immunocompromised individuals. Vaccines for parasites are a challenge in several aspects, including their complex life cycle and mechanisms of evading the immune response. Extracellular vesicles (EVs) are particles released by cells that carry different biomolecules, thus participating in cell-cell communication. EVs released by parasites play a role in the parasite-host interaction. Parasite molecules carried by EVs interact with host immune cells, activating or modulating their function. Thus, unraveling the role of these EVs in immunity could contribute to the identification of molecules with vaccine potential, leading to the development of EV-based vaccines to prevent parasitic diseases. In this chapter, we will discuss the main studies and findings on the protective role of parasite-derived EVs in vaccine preparations.

Trypanosoma cruzi can invade a wide range of non-professional phagocytic cells and does so by subverting the host cell membrane repair mechanism. For this, T. cruzi interacts with and signals to the host cell, leading to the recruitment and fusion of lysosomes to the plasma membrane, which ultimately culminates with the endocytosis of the parasite. To do so, parasite follows a series of steps that include attachment, signaling and formation of the parasitophorous vacuole. For each of these steps a set of proteins have been described to participate, which most likely contribute to its ability to invade different cell types. Besides, intracellular environment also modifies parasite protein expression profile, contributing to its adaptability to the host environment. This chapter will present the different aspects and proteins involved in each of the host cell infection steps.

Extracellular vesicles (EVs) are particles formed by a lipid bilayer, released by various types of cells, plants and pathogens, with their main function being intercellular communication. EVs transport proteins, nucleic acids, and lipids and are potential candidates for clinical applications, therapies, and vaccines. EVs have been extensively studied as biomarkers for disease diagnosis and prognosis because they are found in most biological fluids and contain markers from the cell that released the particle. In the therapeutic field, modified EVs are used as drug delivery systems, offering advantages such as biocompatibility, immunogenicity, and the ability to cross biological barriers. Additionally, vaccines using EVs are being developed due to their immunomodulatory properties, which can induce protective immune responses against infectious diseases and cancer. Despite these advances, there are significant challenges, such as large-scale production, standardization, and approval by regulatory agencies. In this chapter, we describe the use of EVs as biomarkers, therapies, and vaccines against pathogens and cancer, as well as the challenges that scientists encounter in their application. Research on EVs is constantly advancing, and their use represents a revolution in precision medicine. Innovation in this field has the potential to transform diagnostic and therapeutic approaches to various diseases.

Trichomonas vaginalis is a unicellular, flagellated, microaerophilic protozoan that extracellularly colonizes the human urogenital tract, causing trichomoniasis, a highly prevalent sexually transmitted infection (STI). This chapter explores the parasite's complex membrane structures and compositions, including the undulating membrane and its association with paracostal filaments and the costa. Key organelles such as the Golgi apparatus, lysosomes and hydrogenosomes are presented, detailing their structure, composition and biochemical activities. Unlike most eukaryotes, T. vaginalis lacks mitochondria, and instead, its hydrogenosomes are responsible for ATP synthesis, playing a critical role in the parasite's energy metabolism. The role of the plasma membrane in the endocytosis is addressed, alongside the involvement of the cytoskeleton and associated biochemical changes. Additionally, the chapter cover the parasite's interactions with host cells, focusing on the ameboid form of T. vaginalis. It emphasizes the morphological and structural transformations of the plasma membrane that occur during the transition from the piriform shape. Different types of vesicles associated with the plasma membrane, involved in host-parasite interactions, particularly their roles as adhesion molecules and in vesicular transport, are also discussed. The pseudocyst form of T. vaginalis, found under specific microenvironmental conditions, is also highlighted. In this form, the parasite internalizes its flagella, becoming rounded. The plasma membrane structure, composition and organelle modifications, as well as its relationship with host cells are highlighted. Furthermore, the implications of these transformations for the parasite's survival, immune evasion and pathogenic mechanisms are thoroughly reviewed, providing insights into how these membrane-associated adaptations enhance the parasite's pathogenicity.