@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} }
 @article{gomaa_klumpe_luo_selle_barrangou_beisel_2014, title={Programmable Removal of Bacterial Strains by Use of Genome-Targeting CRISPR-Cas Systems}, volume={5}, ISSN={["2150-7511"]}, DOI={10.1128/mbio.00928-13}, abstractNote={ABSTRACT CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of “smart” antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. IMPORTANCE Controlling the composition of microbial populations is a critical aspect in medicine, biotechnology, and environmental cycles. While different antimicrobial strategies, such as antibiotics, antimicrobial peptides, and lytic bacteriophages, offer partial solutions, what remains elusive is a generalized and programmable strategy that can distinguish between even closely related microorganisms and that allows for fine control over the composition of a microbial population. This study demonstrates that RNA-directed immune systems in bacteria and archaea called CRISPR-Cas systems can provide such a strategy. These systems can be employed to selectively and quantitatively remove individual bacterial strains based purely on sequence information, creating opportunities in the treatment of multidrug-resistant infections, the control of industrial fermentations, and the study of microbial consortia. Controlling the composition of microbial populations is a critical aspect in medicine, biotechnology, and environmental cycles. While different antimicrobial strategies, such as antibiotics, antimicrobial peptides, and lytic bacteriophages, offer partial solutions, what remains elusive is a generalized and programmable strategy that can distinguish between even closely related microorganisms and that allows for fine control over the composition of a microbial population. This study demonstrates that RNA-directed immune systems in bacteria and archaea called CRISPR-Cas systems can provide such a strategy. These systems can be employed to selectively and quantitatively remove individual bacterial strains based purely on sequence information, creating opportunities in the treatment of multidrug-resistant infections, the control of industrial fermentations, and the study of microbial consortia.}, number={1}, journal={MBIO}, publisher={American Society for Microbiology}, author={Gomaa, Ahmed A. and Klumpe, Heidi E. and Luo, Michelle L. and Selle, Kurt and Barrangou, Rodolphe and Beisel, Chase L.}, year={2014} }
 @article{barrangou_drake_daubert_foegeding_2006, title={Sensory texture related to large-strain rheological properties of agar/glycerol gels as a model food}, volume={37}, ISSN={["1745-4603"]}, DOI={10.1111/j.1745-4603.2006.00050.x}, abstractNote={Descriptive sensory analysis and large-strain rheological methods were used to evaluate textural characteristics ofagar gels as a model food. The gels were differentiated in the same manner by sensory analysis and rheological properties (P ≤ 0.05), and significant correlations between sensory and rheological properties were reported. First bite and chew-down sensory terms correlated with each other and with fracture properties. Specifically, the first bite sensory term "fracture force" correlated with the chew-down sensory term "chewiness" (r = 0.99, P ≤ 0.001), and both of these sensory terms were correlated with fracture stress (σ f ) and modulus (r = 0.94 - 0.97, P ≤ 0.05). The first bite sensory term "deformability" was positively correlated with fracture strain (r = 0.88, P ≤ 0.05) and negatively correlated with the strain-hardening constant (r = -0.93, P < 0.05). The chew-down property "particle breakdown" was negatively correlated with σ f values (r = -0.97, P ≤ 0.05). For agar gels, each sensory texture term can be linked with a large-strain mechanical property.}, number={3}, journal={JOURNAL OF TEXTURE STUDIES}, author={Barrangou, Lisa M. and Drake, Mary Anne and Daubert, Christopher R. and Foegeding, E. Allen}, year={2006}, month={Jun}, pages={241–262} }
 @article{barrangou_daubert_foegeding_2006, title={Textural properties of agarose gels. I. Rheological and fracture properties}, volume={20}, ISSN={["0268-005X"]}, DOI={10.1016/j.foodhyd.2005.02.019}, abstractNote={Small- and large-strain rheological methods were used to develop rheological profiles of agarose gels, including linear, non-linear, and fracture properties. Gel properties were examined under conditions of varying agarose concentration (0.5–2.5% w/w), glycerol concentration (0–60% w/w), and strain rate (0.0017–0.17 s−1). Small-strain behaviors were primarily elastic with only slight frequency dependence. Large-strain behaviors and fracture properties were dependent upon strain rate, agarose and glycerol concentration. Increasing concentrations of agarose produced an increasingly stronger, more brittle network, while increasing concentrations of glycerol produced an increasingly stronger, more deformable network. All fracture properties and non-linear behaviors increased with increasing strain rate in a similar manner, suggesting a general mechanism responsible for strain rate effects that is similar for non-linear and fracture behavior. Increasing concentrations of agarose and glycerol, respectively, increased and decreased the strain rate dependence of non-linear behavior. Phenomenological models were evaluated for describing non-linear behavior. A second-order polynomial equation was determined to describe the data more accurately than the commonly used BST equation [Blatz, P. J., Sharda, S. C., & Tschoegl, N. W. (1974). Strain energy function for rubberlike materials based on a generalized measure of strain. Transactions of the Society of Rheology, 18 (1) 145–161.], providing an estimated parameter that allowed relative non-linear behavior to be reliably quantified.}, number={2-3}, journal={FOOD HYDROCOLLOIDS}, author={Barrangou, LM and Daubert, CR and Foegeding, EA}, year={2006}, pages={184–195} }
 @article{barrangou_drake_daubert_foegeding_2006, title={Textural properties of agarose gels. II. Relationships between rheological properties and sensory texture}, volume={20}, ISSN={["1873-7137"]}, DOI={10.1016/j.foodhyd.2005.03.013}, abstractNote={Descriptive analysis was used to quantify the perceived hand texture characteristics of agarose gels, and results were compared with previously developed fundamental rheological profiles to determine if relationships could be established. Four texture attributes were used to describe the gels, including ‘hand small-strain force’, ‘hand springiness’, ‘hand fracture force’, and ‘hand fracture deformation’. Gels were differentiated similarly by sensory analysis and fracture properties (p≤0.05). Hand small-strain force and ‘hand-fracture force’ terms were capable of differentiating the gels equally as well, indicating that relative gel strength was perceived similarly with non-destructive and fracture causing deformations. Surprisingly, the hand force terms correlated more highly with fracture modulus (fractures stress/fracture strain) values (r≥0.98, p≤0.001) than fracture stress values (r=0.76–0.82, p≤0.05), suggesting sensory perception of force includes a coupling of stress and strain. The definition of the term hand fracture deformation was very similar to the commonly used sensory term ‘cohesiveness’, and was highly correlated with fracture strain values (r=0.98, p≤0.001). Linear viscoelastic properties could not distinguish gels as sensitively as fracture properties. These findings clearly demonstrate fracture properties are capable of predicting sensory texture properties.}, number={2-3}, journal={FOOD HYDROCOLLOIDS}, author={Barrangou, LM and Drake, M and Daubert, CR and Foegeding, EA}, year={2006}, pages={196–203} }
 @article{mcfeeters_barrangou_barish_morrison_2004, title={Rapid softening of acidified peppers: Effect of oxygen and sulfite}, volume={52}, DOI={10.1021/jf003459533}, number={14}, journal={Journal of Agricultural and Food Chemistry}, author={McFeeters, R. F. and Barrangou, L. M. and Barish, A. O. and Morrison, S. S.}, year={2004}, pages={4554–4557} }