@article{cobian_garlet_hidalgo-cantabrana_barrangou_2021, title={Comparative Genomic Analyses and CRISPR-Cas Characterization of Cutibacterium acnes Provide Insights Into Genetic Diversity and Typing Applications}, volume={12}, ISSN={["1664-302X"]}, DOI={10.3389/fmicb.2021.758749}, abstractNote={Cutibacterium acnes is an important member of the human skin microbiome and plays a critical role in skin health and disease. C. acnes encompasses different phylotypes that have been found to be associated with different skin phenotypes, suggesting a genetic basis for their impact on skin health. Here, we present a comprehensive comparative analysis of 255 C. acnes genomes to provide insights into the species genetic diversity and identify unique features that define various phylotypes. Results revealed a relatively small and open pan genome (6,240 genes) with a large core genome (1,194 genes), and three distinct phylogenetic clades, with multiple robust sub-clades. Furthermore, we identified several unique gene families driving differences between distinct C. acnes clades. Carbohydrate transporters, stress response mechanisms and potential virulence factors, potentially involved in competitive growth and host colonization, were detected in type I strains, which are presumably responsible for acne. Diverse type I-E CRISPR-Cas systems and prophage sequences were detected in select clades, providing insights into strain divergence and adaptive differentiation. Collectively, these results enable to elucidate the fundamental differences among C. acnes phylotypes, characterize genetic elements that potentially contribute to type I-associated dominance and disease, and other key factors that drive the differentiation among clades and sub-clades. These results enable the use of comparative genomics analyses as a robust method to differentiate among the C. acnes genotypes present in the skin microbiome, opening new avenues for the development of biotherapeutics to manipulate the skin microbiota.}, journal={FRONTIERS IN MICROBIOLOGY}, author={Cobian, Natalia and Garlet, Allison and Hidalgo-Cantabrana, Claudio and Barrangou, Rodolphe}, year={2021}, month={Nov} }
 @article{pan_hidalgo-cantabrana_goh_sanozky-dawes_barrangou_2020, title={Comparative Analysis of Lactobacillus gasseri and Lactobacillus crispatus Isolated From Human Urogenital and Gastrointestinal Tracts}, volume={10}, ISSN={["1664-302X"]}, DOI={10.3389/fmicb.2019.03146}, abstractNote={Lactobacillus crispatus and Lactobacillus gasseri are two of the main Lactobacillus species found in the healthy vaginal microbiome and have also previously been identified and isolated from the human gastrointestinal (GI) tract. These two ecological niches are fundamentally different, notably with regards to the epithelial cell type, nutrient availability, environmental conditions, pH, and microbiome composition. Given the dramatic differences between these two environments, we characterized strains within the same Lactobacillus species isolated from either the vaginal or intestinal tract to assess whether they are phenotypically and genetically different. We compared the genomes of the Lactobacillus strains selected in this study for genetic features of interest, and performed a series of comparative phenotypic assays including small intestinal juice and acid resistance, carbohydrate fermentation profiles, lactic acid production, and host interaction with intestinal Caco-2 and vaginal VK2 cell lines. We also developed a simulated vaginal fluid (SVF) to study bacterial growth in a proxy vaginal environment and conducted differential transcriptomic analysis between SVF and standard laboratory MRS medium. Overall, our results show that although strain-specific variation is observed, some phenotypic differences seem associated with the isolation source. We encourage future probiotic formulation to include isolation source and take into consideration genetic and phenotypic features for use at various body sites.}, journal={FRONTIERS IN MICROBIOLOGY}, author={Pan, Meichen and Hidalgo-Cantabrana, Claudio and Goh, Yong Jun and Sanozky-Dawes, Rosemary and Barrangou, Rodolphe}, year={2020}, month={Jan} }
 @misc{hidalgo-cantabrana_goh_barrangou_2019, title={Characterization and Repurposing of Type I and Type II CRISPR-Cas Systems in Bacteria}, volume={431}, ISSN={["1089-8638"]}, DOI={10.1016/j.jmb.2018.09.013}, abstractNote={CRISPR–Cas systems constitute the adaptive immune system of bacteria and archaea, as a sequence-specific nucleic acid targeting defense mechanism. The sequence-specific recognition and cleavage of Cas effector complexes has been harnessed to developed CRISPR-based technologies and drive the genome editing revolution underway, due to their efficacy, efficiency, and ease of implementation in a broad range of organisms. CRISPR-based technologies offer a wide variety of opportunities in genome remodeling and transcriptional regulation, opening new avenues for therapeutic and biotechnological applications. To repurpose CRISPR–Cas systems for these applications, the various elements of the system need to be first identified and functionally characterized in their native host. Bioinformatic tools are first used to identify putative CRISPR arrays and their associated genes, followed by a comprehensive characterization of the CRISPR–Cas system, encompassing predictions for guide and target sequences. Subsequently, interference assays and transcriptomic analyses should be performed to probe the functionality of the CRISPR–Cas system. Once an endogenous CRISPR–Cas system is characterized as functional, they can be readily repurposed by delivering an engineered synthetic CRISPR array or a small RNA guide for targeted gene manipulation. Alternatively, developing a plasmid-based system for heterologous expression of the necessary CRISPR components can enable exploitation in other organisms. Altogether, there is a wide diversity of native CRISPR–Cas systems in many bacteria and most archaea that await functional characterization and repurposing for genome editing applications in prokaryotes.}, number={1}, journal={JOURNAL OF MOLECULAR BIOLOGY}, publisher={Elsevier BV}, author={Hidalgo-Cantabrana, Claudio and Goh, Yong Jun and Barrangou, Rodolphe}, year={2019}, month={Jan}, pages={21–33} }
 @article{martinez_hidalgo-cantabrana_delgado_margolles_sanchez_2019, title={Filling the gap between collection, transport and storage of the human gut microbiota}, volume={9}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-019-44888-8}, abstractNote={Abstract}, journal={SCIENTIFIC REPORTS}, author={Martinez, Noelia and Hidalgo-Cantabrana, Claudio and Delgado, Susana and Margolles, Abelardo and Sanchez, Borja}, year={2019}, month={Jun} }
 @article{hidalgo-cantabrana_gomez_delgado_requena-lopez_queiro-silva_margolles_coto_sanchez_coto-segura_2019, title={Gut microbiota dysbiosis in a cohort of patients with psoriasis}, volume={181}, ISSN={["1365-2133"]}, DOI={10.1111/bjd.17931}, abstractNote={There is increasing evidence of the key role that the gut microbiota plays in inflammatory diseases.}, number={6}, journal={BRITISH JOURNAL OF DERMATOLOGY}, author={Hidalgo-Cantabrana, C. and Gomez, J. and Delgado, S. and Requena-Lopez, S. and Queiro-Silva, R. and Margolles, A. and Coto, E. and Sanchez, B. and Coto-Segura, P.}, year={2019}, month={Dec}, pages={1287–1295} }
 @misc{hidalgo-cantabrana_sanozky-dawes_barrangou_2018, title={Insights into the Human Virome Using CRISPR Spacers from Microbiomes}, volume={10}, ISSN={["1999-4915"]}, url={https://doi.org/10.3390/v10090479}, DOI={10.3390/v10090479}, abstractNote={Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing.}, number={9}, journal={VIRUSES-BASEL}, author={Hidalgo-Cantabrana, Claudio and Sanozky-Dawes, Rosemary and Barrangou, Rodolphe}, year={2018}, month={Sep} }
 @article{morovic_roos_zabel_hidalgo-cantabrana_kiefer_barrangou_2018, title={Transcriptional and Functional Analysis of Bifidobacterium animalis subsp. lactis Exposure to Tetracycline}, volume={84}, ISSN={["1098-5336"]}, url={https://doi.org/10.1128/AEM.01999-18}, DOI={10.1128/AEM.01999-18}, abstractNote={
            Bifidobacterium animalis
            subsp.
            lactis
            is widely used in human food and dietary supplements. Although well documented to be safe,
            B. animalis
            subsp.
            lactis
            strains must not contain transferable antibiotic resistance elements. Many
            B. animalis
            subsp.
            lactis
            strains have different resistance measurements despite being genetically similar, and the reasons for this are not well understood. In the current study, we sought to examine how genomic differences between two closely related industrial
            B. animalis
            subsp.
            lactis
            strains contribute to different resistance levels. This will lead to a better understanding of resistance, identify future targets for analysis of transferability, and expand our understanding of tetracycline resistance in bacteria.
          }, number={23}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, publisher={American Society for Microbiology}, author={Morovic, Wesley and Roos, Paige and Zabel, Bryan and Hidalgo-Cantabrana, Claudio and Kiefer, Anthony and Barrangou, Rodolphe}, editor={Müller, VolkerEditor}, year={2018}, month={Dec} }
 @article{hidalgo-cantabrana_rosa lucena-prieto_antonio moro-garcia_alonso-arias_sanchez_2018, title={Whole fractions from probiotic bacteria induce in vitro Th17 responses in human peripheral blood mononuclear cells}, volume={48}, ISSN={["1756-4646"]}, DOI={10.1016/j.jff.2018.07.038}, abstractNote={Probiotics are used to improve human health due to their capability to induce beneficial effects in gastrointestinal diseases and modulate the immune response. However, scarce information is known about the bacterial active compounds and the metabolic pathways of interaction with immune cells. In the present study, we analyzed the immune response elicited by surface-associated proteins, the whole surface extract (WSE) and the genomic DNA of three strains from the main representative probiotic species for human consumption, L. acidophilus DSM20079T, L. rhamnosus GG, B. longum NCIMB 8809, using an in vitro model of human PBMCs from healthy donors. Eighteen cytokines were quantified using Luminex Technology to understand the immune pathways modulate by bacterial extracts. Overall, the bacterial fractions elicited a different immune response in PBMCs, whereas the isolated DNA was able to induce a higher Th17-like response that could lead to a protective effect in the epithelial barrier function.}, journal={JOURNAL OF FUNCTIONAL FOODS}, author={Hidalgo-Cantabrana, Claudio and Rosa Lucena-Prieto, Maria and Antonio Moro-Garcia, Marco and Alonso-Arias, Rebeca and Sanchez, Borja}, year={2018}, month={Sep}, pages={367–373} }
 @misc{hidalgo-cantabrana_o'flaherty_barrangou_2017, title={CRISPR-based engineering of next-generation lactic acid bacteria}, volume={37}, ISSN={["1879-0364"]}, DOI={10.1016/j.mib.2017.05.015}, abstractNote={The advent of CRISPR-based technologies has opened new avenues for the development of next-generation food microorganisms and probiotics with enhanced functionalities. Building off two decades of functional genomics studies unraveling the genetic basis for food fermentations and host–probiotic interactions, CRISPR technologies offer a wide range of opportunities to engineer commercially-relevant Lactobacillus and Bifidobacteria. Endogenous CRISPR–Cas systems can be repurposed to enhance gene expression or provide new features to improve host colonization and promote human health. Alternatively, engineered CRISPR–Cas systems can be harnessed to genetically modify probiotics and enhance their therapeutic potential to deliver vaccines or modulate the host immune response.}, journal={CURRENT OPINION IN MICROBIOLOGY}, publisher={Elsevier BV}, author={Hidalgo-Cantabrana, Claudio and O'Flaherty, Sarah and Barrangou, Rodolphe}, year={2017}, month={Jun}, pages={79–87} }
 @article{hidalgo-cantabrana_crawley_sanchez_barrangou_2017, title={Characterization and Exploitation of CRISPR Loci in Bifidobacterium longum}, volume={8}, ISSN={["1664-302X"]}, DOI={10.3389/fmicb.2017.01851}, abstractNote={Diverse CRISPR-Cas systems provide adaptive immunity in many bacteria and most archaea, via a DNA-encoded, RNA-mediated, nucleic-acid targeting mechanism. Over time, CRISPR loci expand via iterative uptake of invasive DNA sequences into the CRISPR array during the adaptation process. These genetic vaccination cards thus provide insights into the exposure of strains to phages and plasmids in space and time, revealing the historical predatory exposure of a strain. These genetic loci thus constitute a unique basis for genotyping of strains, with potential of resolution at the strain-level. Here, we investigate the occurrence and diversity of CRISPR-Cas systems in the genomes of various Bifidobacterium longum strains across three sub-species. Specifically, we analyzed the genomic content of 66 genomes belonging to B. longum subsp. longum, B. longum subsp. infantis and B. longum subsp. suis, and identified 25 strains that carry 29 total CRISPR-Cas systems. We identify various Type I and Type II CRISPR-Cas systems that are widespread in this species, notably I-C, I-E, and II-C. Noteworthy, Type I-C systems showed extended CRISPR arrays, with extensive spacer diversity. We show how these hypervariable loci can be used to gain insights into strain origin, evolution and phylogeny, and can provide discriminatory sequences to distinguish even clonal isolates. By investigating CRISPR spacer sequences, we reveal their origin and implicate phages and prophages as drivers of CRISPR immunity expansion in this species, with redundant targeting of select prophages. Analysis of CRISPR spacer origin also revealed novel PAM sequences. Our results suggest that CRISPR-Cas immune systems are instrumental in mounting diversified viral resistance in B. longum, and show that these sequences are useful for typing across three subspecies.}, journal={FRONTIERS IN MICROBIOLOGY}, publisher={Frontiers Media SA}, author={Hidalgo-Cantabrana, Claudio and Crawley, Alexandra B. and Sanchez, Borja and Barrangou, Rodolphe}, year={2017}, month={Sep} }