Biology subjects

Cabezas-Cruz, A.

Publications and source records attributed to Cabezas-Cruz, A..

3 recordsLinked to original sources

bioRxiv2023

Characterization of GEXP15 as a potential regulator of Protein Phosphatase 1 and partner of ribosomal complex in Plasmodium falciparum.

The Protein Phosphatase type 1 catalytic subunit (PP1c) (PF3D7_1414400) operates in combination with various regulatory proteins to specifically direct and control its phosphatase activity. However, little is known about this phosphatase and its regulators in the human malaria parasite, Plasmodium falciparum. To address this gap, we conducted a comprehensive investigation into structural and functional characteristics of a conserved Plasmodium-specific regulator called Gametocyte EXported Protein 15, GEXP15 (PF3D7_1031600). Through in silico analysis, we identified three significant regions of interest in GEXP15: an N-terminal region housing a PP1-interacting RVxF motif, a conserved domain whose function is unknown and a GYF-like motif that potentially facilitates specific protein-protein interactions. To further elucidate the role of GEXP15, we conducted in vitro interaction studies, which demonstrated a direct interaction between GEXP15 and PP1 via the RVxF binding motif. This interaction was found to enhance phosphatase activity of PP1. Additionally, utilizing a transgenic GEXP15-tagged line and live microscopy, we observed high expression of GEXP15 in late asexual stages of the parasite, with localization predominantly in the parasite nucleus. Immunoprecipitation assays followed by mass spectrometry analyses revealed GEXP15s interaction with ribosomal and RNA binding proteins. Furthermore, through pulldown analyses of recombinant functional domains of GEXP15 tagged with a His-tag, we confirmed its binding to the ribosomal complex via the GYF domain. Collectively, our study sheds light on the PfGEXP15-PP1-ribosome interaction, which plays a crucial role in protein translation. These findings suggest that PfGEXP15 could serve as a potential target for the development of malaria drugs.

microbiology↗

bioRxiv2021

Anti-microbiota vaccines modulate the tick microbiome in a taxon-specific manner

Anti-tick microbiota vaccines have been shown to impact tick feeding but its specificity has not been demonstrated. In this study we aimed to investigate the impact of immune targeting of keystone microbiota bacteria on tick performance, and tick microbiota structure and function. Vaccination against Escherichia coli, the selected keystone taxon, increased tick engorgement weight and reduced bacterial diversity in Ixodes ricinus ticks compared to those that fed on mice immunized against Leuconostoc mesenteroides, a non-keystone taxon or mock-immunized group. The abundance of Escherichia-Shigella, but not Leuconostoc was significantly reduced in ticks fed on E. coli-immunized mice and this reduction was correlated with a significant increase in host antibodies (Abs) of the isotype IgM and IgG specific to E. coli proteins. This negative correlation was not observed between the abundance of Leuconostoc in ticks and anti-L. mesenteroides Abs in mice. We also demonstrated by co-occurrence network analysis, that immunization against the keystone bacterium restructure the hierarchy of the microbial community in ticks and that anti-tick microbiota vaccines reduced the resistance of networks to directed removal of taxa. Functional pathways analysis showed that immunization with a live bacterial vaccine can also induce taxon-specific changes in the abundance of pathways. Our results demonstrated that anti-tick microbiota vaccines can modulate the tick microbiome and that the modification is specific to the taxon chosen for host immunization. These results guide interventions for the control of tick infestations and pathogen infection/transmission.

immunology↗

bioRxiv2020

The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms

The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. The characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to advance in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Gal1-3Gal{beta}1-(3)4GlcNAc-R (-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti--Gal IgM/IgG antibodies produced in response to bacterial microbiota. In addition to anti--Gal antibody-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to -Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody response to -Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody titers increased, reduction in anti--Gal IgE, IgM and IgG antibody titers and alteration of anti--Gal antibody isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the -Gal-induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with -Gal epitopes to modify the microbiota and increase the -Gal-induced protective immune response and reduce the severity of COVID-19.

immunology↗