Bachelor of Science, Universidad Nacional Autonoma de Mexico (2009)
Doctor of Philosophy, University of North Carolina, Chapel Hill (2017)
GRINS: Genetic elements that recode assembly-line polyketide synthases and accelerate their diversification.
Proceedings of the National Academy of Sciences of the United States of America
2021; 118 (26)
Assembly-line polyketide synthases (PKSs) are large and complex enzymatic machineries with a multimodular architecture, typically encoded in bacterial genomes by biosynthetic gene clusters. Their modularity has led to an astounding diversity of biosynthesized molecules, many with medical relevance. Thus, understanding the mechanisms that drive PKS evolution is fundamental for both functional prediction of natural PKSs as well as for the engineering of novel PKSs. Here, we describe a repetitive genetic element in assembly-line PKS genes which appears to play a role in accelerating the diversification of closely related biosynthetic clusters. We named this element GRINS: genetic repeats of intense nucleotide skews. GRINS appear to recode PKS protein regions with a biased nucleotide composition and to promote gene conversion. GRINS are present in a large number of assembly-line PKS gene clusters and are particularly widespread in the actinobacterial genus Streptomyces While the molecular mechanisms associated with GRINS appearance, dissemination, and maintenance are unknown, the presence of GRINS in a broad range of bacterial phyla and gene families indicates that these genetic elements could play a fundamental role in protein evolution.
View details for DOI 10.1073/pnas.2100751118
View details for PubMedID 34162709
Genomic features of bacterial adaptation to plants.
2018; 50 (1): 138–50
Plants intimately associate with diverse bacteria. Plant-associated bacteria have ostensibly evolved genes that enable them to adapt to plant environments. However, the identities of such genes are mostly unknown, and their functions are poorly characterized. We sequenced 484 genomes of bacterial isolates from roots of Brassicaceae, poplar, and maize. We then compared 3,837 bacterial genomes to identify thousands of plant-associated gene clusters. Genomes of plant-associated bacteria encode more carbohydrate metabolism functions and fewer mobile elements than related non-plant-associated genomes do. We experimentally validated candidates from two sets of plant-associated genes: one involved in plant colonization, and the other serving in microbe-microbe competition between plant-associated bacteria. We also identified 64 plant-associated protein domains that potentially mimic plant domains; some are shared with plant-associated fungi and oomycetes. This work expands the genome-based understanding of plant-microbe interactions and provides potential leads for efficient and sustainable agriculture through microbiome engineering.
View details for PubMedID 29255260
Design of synthetic bacterial communities for predictable plant phenotypes.
2018; 16 (2): e2003962
Specific members of complex microbiota can influence host phenotypes, depending on both the abiotic environment and the presence of other microorganisms. Therefore, it is challenging to define bacterial combinations that have predictable host phenotypic outputs. We demonstrate that plant-bacterium binary-association assays inform the design of small synthetic communities with predictable phenotypes in the host. Specifically, we constructed synthetic communities that modified phosphate accumulation in the shoot and induced phosphate starvation-responsive genes in a predictable fashion. We found that bacterial colonization of the plant is not a predictor of the plant phenotypes we analyzed. Finally, we demonstrated that characterizing a subset of all possible bacterial synthetic communities is sufficient to predict the outcome of untested bacterial consortia. Our results demonstrate that it is possible to infer causal relationships between microbiota membership and host phenotypes and to use these inferences to rationally design novel communities.
View details for DOI 10.1371/journal.pbio.2003962
View details for PubMedID 29462153
View details for PubMedCentralID PMC5819758
Root microbiota drive direct integration of phosphate stress and immunity
2017; 543 (7646): 513-?
Plants live in biogeochemically diverse soils with diverse microbiota. Plant organs associate intimately with a subset of these microbes, and the structure of the microbial community can be altered by soil nutrient content. Plant-associated microbes can compete with the plant and with each other for nutrients, but may also carry traits that increase the productivity of the plant. It is unknown how the plant immune system coordinates microbial recognition with nutritional cues during microbiome assembly. Here we establish that a genetic network controlling the phosphate stress response influences the structure of the root microbiome community, even under non-stress phosphate conditions. We define a molecular mechanism regulating coordination between nutrition and defence in the presence of a synthetic bacterial community. We further demonstrate that the master transcriptional regulators of phosphate stress response in Arabidopsis thaliana also directly repress defence, consistent with plant prioritization of nutritional stress over defence. Our work will further efforts to define and deploy useful microbes to enhance plant performance.
View details for DOI 10.1038/nature21417
View details for Web of Science ID 000397018000043
View details for PubMedID 28297714
View details for PubMedCentralID PMC5364063
Understanding and exploiting plant beneficial microbes.
Current opinion in plant biology
2017; 38: 155–63
After a century of incremental research, technological advances, coupled with a need for sustainable crop yield increases, have reinvigorated the study of beneficial plant-microbe interactions with attention focused on how microbiomes alter plant phenotypes. We review recent advances in plant microbiome research, and describe potential applications for increasing crop productivity. The phylogenetic diversity of plant microbiomes is increasingly well characterized, and their functional diversity is becoming more accessible. Large culture collections are available for controlled experimentation, with more to come. Genetic resources are being brought to bear on questions of microbiome function. We expect that microbial amendments of varying complexities will expose rules governing beneficial plant-microbe interactions contributing to plant growth promotion and disease resistance, enabling more sustainable agriculture.
View details for DOI 10.1016/j.pbi.2017.04.018
View details for PubMedID 28622659
View details for PubMedCentralID PMC5561662
- Giving back to the community: microbial mechanisms of plant-soil interactions FUNCTIONAL ECOLOGY 2016; 30 (7): 1043-1052
- Salicylic acid modulates colonization of the root microbiome by specific bacterial taxa SCIENCE 2015; 349 (6250): 860-864
The Antipsychotic Olanzapine Interacts with the Gut Microbiome to Cause Weight Gain in Mouse
2014; 9 (12)
The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.
View details for DOI 10.1371/journal.pone.0115225
View details for Web of Science ID 000346607100063
View details for PubMedID 25506936
View details for PubMedCentralID PMC4266663
Promoter-proximal CCCTC-factor binding is associated with an increase in the transcriptional pausing index
2013; 29 (12): 1485-1487
It has been known for more than 2 decades that after RNA polymerase II (RNAPII) initiates transcription, it can enter into a paused or stalled state immediately downstream of the transcription start site before productive elongation. Recent advances in high-throughput genomic technologies facilitated the discovery that RNAPII pausing at promoters is a widespread physiologically regulated phenomenon. The molecular underpinnings of pausing are incompletely understood. The CCCTC-factor (CTCF) is a ubiquitous nuclear factor that has diverse regulatory functions, including a recently discovered role in promoting RNAPII pausing at splice sites.In this study, we analyzed CTCF binding sites and nascent transcriptomic data from three different cell types, and found that promoter-proximal CTCF binding is significantly associated with RNAPII pausing.
View details for DOI 10.1093/bioinformatics/bts596
View details for Web of Science ID 000320065400001
View details for PubMedID 23047559
View details for PubMedCentralID PMC3673211
Defining the core Arabidopsis thaliana root microbiome
2012; 488 (7409): 86-?
Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation. Colonization of the root occurs despite a sophisticated plant immune system, suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plant-microbe interactions derived from complex soil communities.
View details for DOI 10.1038/nature11237
View details for Web of Science ID 000307010700038
View details for PubMedID 22859206
View details for PubMedCentralID PMC4074413
Moonlighting Peptides with Emerging Function
2012; 7 (7)
Hunter-killer peptides combine two activities in a single polypeptide that work in an independent fashion like many other multi-functional, multi-domain proteins. We hypothesize that emergent functions may result from the combination of two or more activities in a single protein domain and that could be a mechanism selected in nature to form moonlighting proteins. We designed moonlighting peptides using the two mechanisms proposed to be involved in the evolution of such molecules (i.e., to mutate non-functional residues and the use of natively unfolded peptides). We observed that our moonlighting peptides exhibited two activities that together rendered a new function that induces cell death in yeast. Thus, we propose that moonlighting in proteins promotes emergent properties providing a further level of complexity in living organisms so far unappreciated.
View details for DOI 10.1371/journal.pone.0040125
View details for Web of Science ID 000306406700022
View details for PubMedID 22808104
View details for PubMedCentralID PMC3396687