Group photo. Some members of the group.
Our group investigates the prokaryotic-eukaryotic mutualistic symbiosis, widely distributed in nature and with significant impact on animal evolution (Moya et al., 2008). In endosymbiosis, bacteria live within specialized cells (bacteriocytes) of the host, are vertically transmitted, and have evolved genomically and functionally to complement the needs of the host without being perceived as infectious agents. In addition, there are ectosymbioses, associations in which a large number of bacterial species are housed in different organs of the host, constituting its microbiota. Massive sequencing has revealed a complex intestinal microbiota in animals, which performs essential functions, contributing to correct nutrition, physiology and host immunity (Moya and Ferrer, 2016).
During the last 15 years, our characterization of the genome of multiple endosymbionts of insects that feed on phloem (see previous review in SEM @ forum nº 58, 2014), has contributed significantly to understanding their role in contributing nutrients deficient in the host's diet ( Latorre and Manzano-Marín, 2017; López-Madrigal and Gil, 2017). But we have also characterized several strains of Blattabacterium, cockroach endosymbiont, despite being omnivorous (López-Sánchez et al., 2009). Currently, our model symbiote system is Germanic blattella.
Why Blattella?
Cockroaches are paradigmatic to study symbiosis, since in each individual they coexist Blattabacterium (in bacteriocytes of the fat body) and a complex ectosymbiont community (in the hindgut; Pérez-Cobas et al., 2015). This makes it possible to study, throughout the development of the insect, the dialogue between two spatially separated symbiotic systems. We analyze the changes that occur when the microbiota is subjected to disturbances (changes in diet, use of antibiotics with different spectrum of activity ...).
Blattabacterium is transmitted from mothers to oocytes, being the only bacteria present in the ootheca, while the intestinal microbiota is acquired horizontally from the environment, mainly through feces (Carrasco et al., 2014; Roses et al., 2018). Meta-omic studies have allowed us to model collaboration Blattabacterium-Insect to synthesize glutamine from uric acid stored in uricocytes (other specialized cells of the fatty body; Patiño-Navarrete et al., 2014). We continue to try to find out the role of the gut microbiota in the physiology of the insect and if there is a dialogue between both symbiotic systems.
Understanding the ensemble also involves evaluating how the host controls both symbiotic systems. We are currently studying the innate immunity of B. Germanic, looking for antimicrobial peptides (AMP) in bacteriocytes and hindgut. These AMPs could also increase membrane permeability, affecting metabolic flux at the host-symbiont interface, allowing metabolic integration with the host.
And now, Bartonella
One of the most explored approaches in the new synthetic biology is the simplification of natural cells, eliminating non-essential genes or genes with negative effects, to generate an adequate chassis to which to add genetic modules to perform a function of interest (Moya et al., 2009 ). The genomic study of endosymbionts contributed to the definition of minimal genomes (Gil, 2014), but these bacteria are not culturable and cannot be manipulated experimentally. Therefore, in our current project, we take advantage of the possibility of cultivating Bartonella, a facultative endosymbiont of mammalian cells, as a model to develop, in the long term, an endosymbiont chassis that could be used for therapeutic purposes (eg, directed against hematophagous pathogens or to transiently introduce a gene of interest). What Bartonella it is a fastidious organism (it takes up to a week to see colonies on a plate), we have started with its metabolic modeling to design an improved culture medium. The next step will be its experimental modification to better understand the model for future interventions.
The human microbiome is our other big research program. It is often claimed that it is all beneficial, but it is far from being proven. We have evidence that the microbiota is coupling to the host, probably until it is optimal in the reproductive phase, uncoupling at advanced ages. We have shown, for example, that the production by the intestinal microbiota of tryptophan and indole, essential in our metabolism, is adequate during childhood, but progressively declines to almost zero in the elderly (Ruiz-Ruiz et al, 2019). But we have well-founded suspicions that in the intestinal microbiota there is a nucleus of microorganisms that have co-evolved with the human host, authentic mutualistic symbionts. Our goal is to determine who they are and how they contribute to normal host physiology throughout life.
Defining a normal microbiota is key from a clinical point of view. Analyzing the changes in the intestinal microbiota in time series, we have formulated a mathematical criterion, based on two coefficients of Taylor's power law (variability of taxa with time and coefficient of the power law), which define when a microbiota is healthy or dysbiotic (Martí et al., 2017).
Some relevant publications of the group cited in the text
Carrasco P, Pérez-Cobas AE, van de Pol C, et al. (2014). Succession of the gut microbiota in the cockroack Blattella germanica. Int Microbiol 17: 99-109.
Gil R. (2014). The minimal gene-set machinery. In Encyclopedia of Molecular Cell Biology and Molecular Medicine: Synthetic Biology, 2nd edition. Meyers RA (ed.). Wiley-VCH Verlag GmbH & What. pp. 1-36.
Latorre A and Manzano-Marin A. (2017). Dissecting genome reduction and trait loss in insect endosymbionts. Ann NY Acad Sci 1389: 52-75.
López-Madrigal S and Gil R. (2017). Et tu, Brute? Not even intracellular mutualistic symbionts escape horizontal gene transfer. Genes 8: 247.
López-Sánchez MJ, Neef A, Peretó J, et al. (2009). Evolutionary convergence and nitrogen metabolism in Blattabacterium strain Bge, primary endosymbiont of the cockroach Blattella germanica. PLoS Genet 5: e1000721.
Martí JM, Martínez-Martínez D, Rubio T, et al. (2017). Health and disease imprinted in the time variability of the human microbiome. mSystems 2: e00144-16.
Moya A, Peretó J, Gil R, Latorre A. (2008). Learning how to live together: Genomic insights into prokaryote-animal symbioses. Nat Rev Genet 9: 218-29.
Moya A, Gil R, Latorre A, et al. (2019). Towards minimal bacterial cells: evolution vs. design. FEMS Microbiol Reve 33: 225-35.
Moya A and Ferrer M. (2016). Functional redundancy-induced stability of gut microbiota subjected to disturbance. Trends Microbiol 24: 402-13.
Patiño-Navarrete R, Piulachs MD, Belles X, et al. (2014). The cockroach Blattella germanica obtains nitrogen from uric acid through a metabolic pathway shared with its bacterial endosymbiont. Biol Lett 10: 20140407.
Pérez-Cobas A, Maiques E, Angelova A, et al. (2015). Diet shapes the gut microbiota of the omnivorous cockroach Blatella germanica. FEMS Microbiol Ecol 91 pii: fiv022.
Rosas T, García-Ferris C, Domínguez-Santos R, et al. (2018). Rifampicin treatment of Blattella germanica evidences a fecal transmission route of their gut microbiota. FEMS Microbiol Ecol 94: fiy002.
Ruiz-Ruiz S, Sanchez-Carrillo S, Ciordia S, et al. (2019). Functional microbiome deficits associated with ageing: chronological age-threshold. Aging Cell, aceptado.