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Gautam dantas

Terence S Crofts, Andrew J Gasparrini, Gautam Dantas
Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities...
April 10, 2017: Nature Reviews. Microbiology
Mitchell W Pesesky, Tahir Hussain, Meghan Wallace, Sanket Patel, Saadia Andleeb, Carey-Ann D Burnham, Gautam Dantas
The time-to-result for culture-based microorganism recovery and phenotypic antimicrobial susceptibility testing necessitates initial use of empiric (frequently broad-spectrum) antimicrobial therapy. If the empiric therapy is not optimal, this can lead to adverse patient outcomes and contribute to increasing antibiotic resistance in pathogens. New, more rapid technologies are emerging to meet this need. Many of these are based on identifying resistance genes, rather than directly assaying resistance phenotypes, and thus require interpretation to translate the genotype into treatment recommendations...
2016: Frontiers in Microbiology
Robert F Potter, Alaric W D'Souza, Gautam Dantas
Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Manish Boolchandani, Sanket Patel, Gautam Dantas
The construction and screening of metagenomic expression libraries has great potential to identify novel genes and their functions. Here, we describe metagenomic library preparation from fecal DNA, screening of libraries for antibiotic resistance genes (ARGs), massively parallel DNA sequencing of the enriched DNA fragments, and a computational pipeline for high-throughput assembly and annotation of functionally selected DNA.
2017: Methods in Molecular Biology
Boahemaa Adu-Oppong, Andrew J Gasparrini, Gautam Dantas
Microbial communities contain diverse bacteria that play important roles in every environment. Advances in sequencing and computational methodologies over the past decades have illuminated the phylogenetic and functional diversity of microbial communities from diverse habitats. Among the activities encoded in microbiomes are the abilities to synthesize and resist small molecules, yielding antimicrobial activity. These functions are of particular interest when viewed in light of the public health emergency posed by the increase in clinical antimicrobial resistance and the dwindling antimicrobial discovery and approval pipeline, and given the intimate ecological and evolutionary relationship between antimicrobial biosynthesis and resistance...
January 2017: Annals of the New York Academy of Sciences
Samuel L Díaz-Muñoz, Amy M Boddy, Gautam Dantas, Christopher M Waters, Judith L Bronstein
Biologists have taken the concept of organism largely for granted. However, advances in the study of chimerism, symbiosis, bacterial-eukaryote associations, and microbial behavior have prompted a redefinition of organisms as biological entities exhibiting low conflict and high cooperation among their parts. This expanded view identifies organisms in evolutionary time. However, the ecological processes, mechanisms, and traits that drive the formation of organisms remain poorly understood. Recognizing that organismality can be context dependent, we advocate elucidating the ecological contexts under which entities do or do not act as organisms...
December 2016: Evolution; International Journal of Organic Evolution
Molly K Gibson, Bin Wang, Sara Ahmadi, Carey-Ann D Burnham, Phillip I Tarr, Barbara B Warner, Gautam Dantas
Development of the preterm infant gut microbiota is emerging as a critical research priority(1). Since preterm infants almost universally receive early and often extended antibiotic therapy(2), it is important to understand how these interventions alter gut microbiota development(3-6). Analysis of 401 stools from 84 longitudinally sampled preterm infants demonstrates that meropenem, cefotaxime and ticarcillin-clavulanate are associated with significantly reduced species richness. In contrast, vancomycin and gentamicin, the antibiotics most commonly administered to preterm infants, have non-uniform effects on species richness, but these can be predicted with 85% accuracy based on the relative abundance of only two bacterial species and two antibiotic resistance (AR) genes at treatment initiation...
March 7, 2016: Nature Microbiology
Andrew J Gasparrini, Terence S Crofts, Molly K Gibson, Phillip I Tarr, Barbara B Warner, Gautam Dantas
The gut microbiota plays important roles in nutrient absorption, immune system development, and pathogen colonization resistance. Perturbations early in life may be detrimental to host health in the short and the long-term. Antibiotics are among the many factors that influence the development of the microbiota. Because antibiotics are heavily administered during the first critical years of gut microbiota development, it is important to understand the effects of these interventions. Infants, particularly those born prematurely, represent an interesting population because they receive early and often extensive antibiotic therapy in the first months after birth...
September 2, 2016: Gut Microbes
Aki Yoneda, Bruce J Wittmann, Jeremy D King, Robert E Blankenship, Gautam Dantas
Acaryochloris species are a genus of cyanobacteria that utilize chlorophyll (chl) d as their primary chlorophyll molecule during oxygenic photosynthesis. Chl d allows Acaryochloris to harvest red-shifted light, which gives them the ability to live in filtered light environments that are depleted in visible light. Although genomes of multiple Acaryochloris species have been sequenced, their analysis has not revealed how chl d is synthesized. Here, we demonstrate that Acaryochloris sp. CCMEE 5410 cells undergo chlorosis by nitrogen depletion and exhibit robust regeneration of chl d by nitrogen repletion...
August 2016: Photosynthesis Research
Erica C Pehrsson, Pablo Tsukayama, Sanket Patel, Melissa Mejía-Bautista, Giordano Sosa-Soto, Karla M Navarrete, Maritza Calderon, Lilia Cabrera, William Hoyos-Arango, M Teresita Bertoli, Douglas E Berg, Robert H Gilman, Gautam Dantas
Antibiotic-resistant infections annually claim hundreds of thousands of lives worldwide. This problem is exacerbated by exchange of resistance genes between pathogens and benign microbes from diverse habitats. Mapping resistance gene dissemination between humans and their environment is a public health priority. Here we characterized the bacterial community structure and resistance exchange networks of hundreds of interconnected human faecal and environmental samples from two low-income Latin American communities...
May 12, 2016: Nature
Amy Langdon, Nathan Crook, Gautam Dantas
The widespread use of antibiotics in the past 80 years has saved millions of human lives, facilitated technological progress and killed incalculable numbers of microbes, both pathogenic and commensal. Human-associated microbes perform an array of important functions, and we are now just beginning to understand the ways in which antibiotics have reshaped their ecology and the functional consequences of these changes. Mounting evidence shows that antibiotics influence the function of the immune system, our ability to resist infection, and our capacity for processing food...
April 13, 2016: Genome Medicine
Aki Yoneda, William R Henson, Nicholas K Goldner, Kun Joo Park, Kevin J Forsberg, Soo Ji Kim, Mitchell W Pesesky, Marcus Foston, Gautam Dantas, Tae Seok Moon
Lignin-derived (e.g. phenolic) compounds can compromise the bioconversion of lignocellulosic biomass to fuels and chemicals due to their toxicity and recalcitrance. The lipid-accumulating bacterium Rhodococcus opacus PD630 has recently emerged as a promising microbial host for lignocellulose conversion to value-added products due to its natural ability to tolerate and utilize phenolics. To gain a better understanding of its phenolic tolerance and utilization mechanisms, we adaptively evolved R. opacus over 40 passages using phenol as its sole carbon source (up to 373% growth improvement over wild-type), and extensively characterized two strains from passages 33 and 40...
March 18, 2016: Nucleic Acids Research
Andrew S Krueger, Christian Munck, Gautam Dantas, George M Church, James Galagan, Joseph Lehár, Morten O A Sommer
Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of the most widely used antibiotic treatments. Here we extend FBA modeling to simulate responses to chemical inhibitors at varying concentrations, by diverting enzymatic flux to a waste reaction. This flux diversion yields very similar qualitative predictions to prior methods for single target activity...
2016: PloS One
James Kaminski, Molly K Gibson, Eric A Franzosa, Nicola Segata, Gautam Dantas, Curtis Huttenhower
Profiling microbial community function from metagenomic sequencing data remains a computationally challenging problem. Mapping millions of DNA reads from such samples to reference protein databases requires long run-times, and short read lengths can result in spurious hits to unrelated proteins (loss of specificity). We developed ShortBRED (Short, Better Representative Extract Dataset) to address these challenges, facilitating fast, accurate functional profiling of metagenomic samples. ShortBRED consists of two components: (i) a method that reduces reference proteins of interest to short, highly representative amino acid sequences ("markers") and (ii) a search step that maps reads to these markers to quantify the relative abundance of their associated proteins...
December 2015: PLoS Computational Biology
Kevin J Forsberg, Sanket Patel, Evan Witt, Bin Wang, Tyler D Ellison, Gautam Dantas
The production of fuels or chemicals from lignocellulose currently requires thermochemical pretreatment to release fermentable sugars. These harsh conditions also generate numerous small-molecule inhibitors of microbial growth and fermentation, limiting production. We applied small-insert functional metagenomic selections to discover genes that confer microbial tolerance to these inhibitors, identifying both individual genes and general biological processes associated with tolerance to multiple inhibitory compounds...
November 6, 2015: Applied and Environmental Microbiology
Patrick R Gonzales, Mitchell W Pesesky, Renee Bouley, Anna Ballard, Brent A Biddy, Mark A Suckow, William R Wolter, Valerie A Schroeder, Carey-Ann D Burnham, Shahriar Mobashery, Mayland Chang, Gautam Dantas
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple β-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA subspecies N315 and 72 other clinical MRSA isolates in vitro and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents...
November 2015: Nature Chemical Biology
Molly K Gibson, Terence S Crofts, Gautam Dantas
The microbial communities colonizing the human gut are tremendously diverse and highly personal. The composition and function of the microbiota play important roles in human health and disease, and considerable research has focused on understanding the ecological forces shaping these communities. While it is clear that factors such as diet, genotype of the host, and environment influence the adult gut microbiota community composition, recent work has emphasized the importance of early-life assembly dynamics in both the immediate and long-term personalized nature of the gut microbiota...
October 2015: Current Opinion in Microbiology
Jose C Clemente, Erica C Pehrsson, Martin J Blaser, Kuldip Sandhu, Zhan Gao, Bin Wang, Magda Magris, Glida Hidalgo, Monica Contreras, Óscar Noya-Alarcón, Orlana Lander, Jeremy McDonald, Mike Cox, Jens Walter, Phaik Lyn Oh, Jean F Ruiz, Selena Rodriguez, Nan Shen, Se Jin Song, Jessica Metcalf, Rob Knight, Gautam Dantas, M Gloria Dominguez-Bello
Most studies of the human microbiome have focused on westernized people with life-style practices that decrease microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami Amerindian village with no documented previous contact with Western people. These Yanomami harbor a microbiome with the highest diversity of bacteria and genetic functions ever reported in a human group...
April 3, 2015: Science Advances
Aimee M Moore, Sara Ahmadi, Sanket Patel, Molly K Gibson, Bin Wang, I Malick Ndao, Elena Deych, William Shannon, Phillip I Tarr, Barbara B Warner, Gautam Dantas
[This corrects the article DOI: 10.1186/s40168-015-0090-9.].
2015: Microbiome
Aimee M Moore, Sara Ahmadi, Sanket Patel, Molly K Gibson, Bin Wang, Malick I Ndao, Elena Deych, William Shannon, Phillip I Tarr, Barbara B Warner, Gautam Dantas
BACKGROUND: The early life of the human host marks a critically important time for establishment of the gut microbial community, yet the developmental trajectory of gut community-encoded resistance genes (resistome) is unknown. We present a longitudinal study of the fecal antibiotic resistome of healthy amoxicillin-exposed and antibiotic-naive twins and their mothers during the first year of life. RESULTS: We extracted metagenomic DNA (mgDNA) from fecal samples collected from three healthy twin pairs at three timepoints (1 or 2 months, 6 or 7 months, and 11 months) and from their mothers (collected at delivery)...
2015: Microbiome
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