Vladimir López

Instituto de Investigación en Recursos Cinegéticos

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José de la Fuente

Consejo Superior de Investigaciones Científicas

Christian Gortázar

University of Castilla-La Mancha

Pilar Alberdi

Instituto de Investigación en Recursos Cinegéticos

Margarita Villar

Instituto de Investigación en Recursos Cinegéticos

Alejandro Cabezas‐Cruz

Bipar

Joaquín Vicente

Instituto de Investigación en Recursos Cinegéticos

Marinela Contreras

Instituto de Investigación en Recursos Cinegéticos

Joseba M. Garrido

NEIKER, the Basque Institute for Agricultural Research and Development

Iratxe Díez‐Delgado

Consejo Superior de Investigaciones Científicas

Ramón A. Juste

Euskadiko Parke Teknologikoa

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Instituto de Investigación en Recursos Cinegéticos

Consejo Superior de Investigaciones Científicas

University of Castilla-La Mancha

Regional Government of Castile-La Mancha

Universidad Complutense de Madrid

Instituto de Salud Carlos III

Centro de Investigación Biomédica en Red

AgroBio

Centro de Investigação em Biodiversidade e Recursos Genéticos

Campo Arqueologico de Mertola

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The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

Parasites & Vectors (2016)

Margarita Villar Vladimir López Nieves Ayllón Alejandro Cabezas‐Cruz Juan Antonio López

The intracellular bacteria Anaplasma phagocytophilum are emerging zoonotic pathogens affecting human and animal health, and a good model for the study of tick-host-pathogen interactions. This tick-borne pathogen is transmitted by Ixodes scapularis in the United States where it causes human granulocytic anaplasmosis. Tick midguts and salivary glands play a major role during tick feeding and development, and in pathogen acquisition, multiplication and transmission. Vertebrate host proteins are found in tick midguts after feeding and have been described in the salivary glands of fed and unfed ticks, suggesting a role for these proteins during tick feeding and development. Furthermore, recent results suggested the hypothesis that pathogen infection affects tick metabolic processes to modify host protein digestion and persistence in the tick with possible implications for tick physiology and pathogen life-cycle. To address this hypothesis, herein we used I. scapularis female ticks fed on uninfected and A. phagocytophilum-infected sheep to characterize host protein content in midguts and salivary glands by proteomic analysis of tick tissues. The results evidenced a clear difference in the host protein content between tick midguts and salivary glands in response to infection suggesting that A. phagocytophilum selectively manipulates the levels of vertebrate host proteins in ticks in a tissue-specific manner to facilitate pathogen infection, multiplication and transmission while preserving tick feeding and development. The mechanisms by which A. phagocytophilum manipulates the levels of vertebrate host proteins are not known, but the results obtained here suggested that it might include the modification of proteolytic pathways. The results of this study provided evidence to support that A. phagocytophilum affect tick proteolytic pathways to selectively manipulate the levels of vertebrate host proteins in a tissue-specific manner to increase tick vector capacity. Investigating the biological relevance of host proteins in tick biology and pathogen infection and the mechanisms used by A. phagocytophilum to manipulate host protein content is essential to advance our knowledge of tick-host-pathogen molecular interactions. These results have implications for the identification of new targets for the development of vaccines for the control of tick-borne diseases.

Anaplasma phagocytophilum

Ixodes scapularis

Parasitology

Anaplasmosis

Tick-borne disease

Entomology

Intracellular parasite

Amblyomma americanum

10.1186/s13071-016-1747-3

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Citations (32)

Heat‐inactivated Mycobacterium bovis protects zebrafish against mycobacteriosis

Journal of Fish Diseases (2018)

Vladimir López María Á. Risalde Marinela Contreras Lourdes Mateos‐Hernández Joaquín Vicente

Control of mycobacterial infection constitutes a priority for human and animal health worldwide. However, effective vaccines are needed for the control of human and animal tuberculosis (TB). Adult zebrafish have become a useful model for studying the pathophysiology of mycobacterial infection and for the development of novel interventions for TB control and prevention. Recently, parenteral and oral immunization with the heat-inactivated Mycobacterium bovis vaccine (M. bovis IV) protected wild boar against TB. The objectives of this study were to provide additional support for the role of M. bovis IV in TB control using the zebrafish model and to conduct the first trial with this vaccine for the control of fish mycobacteriosis. The results showed that M. bovis IV protected zebrafish against mycobacteriosis caused by low and high infection doses of Mycobacterium marinum and provided evidence suggesting that the protective mechanism elicited by M. bovis IV in zebrafish as in other species is based on the activation of the innate immune response through the C3 pathway, with a role for the regulatory protein Akr2 in this process. These results encourage the use of M. bovis IV for TB control in different species.

Mycobacterium marinum

Tuberculosis vaccines

10.1111/jfd.12847

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Citations (28)

A metaproteomics approach reveals changes in mandibular lymph node microbiota of wild boar naturally exposed to an increasing trend of Mycobacterium tuberculosis complex infection

Tuberculosis (2018)

João Queirós Margarita Villar Angélica Hernández-Jarguín Vladimir López Isabel G. Fernández de Mera

Metaproteomics

Mycobacterium tuberculosis complex

Pestivirus

10.1016/j.tube.2018.12.003

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Citations (3)

Control of mycobacteriosis in zebrafish ( Danio rerio ) mucosally vaccinated with heat-inactivated Mycobacterium bovis

Vaccine (2018)

María Á. Risalde Vladimir López Marinela Contreras Lourdes Mateos‐Hernández Christian Gortázar

Mycobacterium marinum

Tuberculosis vaccines

10.1016/j.vaccine.2018.06.042

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Citations (29)

Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

PLoS neglected tropical diseases (2016)

Vladimir López Margarita Villar João Queirós Joaquín Vicente Lourdes Mateos‐Hernández

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen multiplication and promote survival, facilitating pathogen transmission.

Wild boar

10.1371/journal.pntd.0004541

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Citations (13)

Common Strategies, Different Mechanisms to Infect the Host: Anaplasma and Mycobacterium

InTech eBooks (2018)

Vladimir López Pilar Alberdi José de la Fuente

Intracellular bacteria such as Anaplasma spp. and Mycobacterium spp. pose a risk to human and animal populations worldwide. The main function of immune response cells is to eliminate invading pathogens. However, pathogens can deregulate host cell function and turn defense cells into suitable hosts. Intracellular bacterial have a smaller genome, compared to the host cell, thus requiring efficient mechanisms for survival and persistence within the host by inducing sustained changes in cell function and immune response. Bacterial epigenetic regulation of host cell gene transcription appears to be a general mechanism that enhances pathogen survival while altering host cell function and facilitating infection. Anaplasma phagocytophilum leads to modified host cell gene transcription and phenotype by epigenetically altering host chromatin. Mycobacterial infection of human cells also results in host gene silencing using a mechanism that involves HDAC complex formation and histone deacetylation. Membrane proteins are essential for cell invasion in both pathogens, and can regulate and protect the pathogen against the host response. Understanding the mechanisms employed by these bacteria to infect the host could contribute to develop effective interventions for the control of tuberculosis and anaplasmosis. This review focuses on the common strategies employed by two zoonotic pathogens, Anaplasma and Mycobacterium spp., highlighting also the different mechanisms used to infect host cells.

Intracellular parasite

Host–pathogen interaction

Anaplasma phagocytophilum

10.5772/intechopen.71535

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Citations (0)

Complete Genome Sequences of Field Isolates of Mycobacterium bovis and Mycobacterium caprae

Genome Announcements (2015)

José de la Fuente Iratxe Díez‐Delgado Marinela Contreras Joaquín Vicente Alejandro Cabezas‐Cruz

Here we report the complete genome sequences of field isolates of Mycobacterium bovis and the related mycobacterial species, Mycobacterium caprae. The genomes of three M. bovis (MB1, MB3, MB4) and one M. caprae (MB2) field isolates with different virulence, prevalence, and host distribution phenotypes were sequenced.

10.1128/genomea.00247-15

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Citations (6)

Use of Graph Theory to Characterize Human and Arthropod Vector Cell Protein Response to Infection With Anaplasma phagocytophilum

Frontiers in Cellular and Infection Microbiology (2018)

Agustı́n Estrada-Peña Margarita Villar Sara Artigas-Jerónimo Vladimir López Pilar Alberdi

One of the major challenges in modern biology is the use of large omics datasets for the characterization of complex processes such as cell response to infection. These challenges are even bigger when analyses need to be performed for comparison of different species including model and non-model organisms. To address these challenges, the graph theory was applied to characterize the tick vector and human cell protein response to infection with Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis. A network of interacting proteins and cell processes clustered in biological pathways, and ranked with indexes representing the topology of the proteome was prepared. The results demonstrated that networks of functionally interacting proteins represented in both infected and uninfected cells can describe the complete set of host cell processes and metabolic pathways, providing a deeper view of the comparative host cell response to pathogen infection. The results demonstrated that changes in the tick proteome were driven by modifications in protein representation in response to A. phagocytophilum infection. Pathogen infection had a higher impact on tick than human proteome. Since most proteins were linked to several cell processes, the changes in protein representation affected simultaneously different biological pathways. The method allowed discerning cell processes that were affected by pathogen infection from those that remained unaffected. The results supported that human neutrophils but not tick cells limit pathogen infection through differential representation of ras-related proteins. This methodological approach could be applied to other host-pathogen models to identify host derived key proteins in response to infection that may be used to develop novel control strategies for arthropod-borne pathogens.

Anaplasma phagocytophilum

Proteome

10.3389/fcimb.2018.00265

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Citations (24)

Additional file 3: Dataset S2. of The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis

Figshare (2016)

Margarita Villar Vladimir López Nieves Ayllón Alejandro Cabezas‐Cruz Juan Antonio López

Proteomics results for sheep host proteins in tick tissues. (XLSX 208 kb)

Ixodes scapularis

Anaplasma phagocytophilum

10.6084/m9.figshare.c.3629255_d3