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Eric pamer

Eric G Pamer
Bacterial species constituting the intestinal microbiota are implicated in maintenance of health but also pathogenesis of inflammatory disease. The compositional complexity of the microbiota and metabolic interdependencies of microbial species challenge our ability to attribute host responses to specific bacterial strains. Studies using gnotobiotic mice, however, are providing important insights.
March 31, 2017: Trends in Molecular Medicine
Yeon Joo Lee, Esther P Arguello, Robert R Jenq, Eric Littmann, Grace J Kim, Liza C Miller, Lilan Ling, Cesar Figueroa, Elizabeth Robilotti, Miguel-Angel Perales, Juliet N Barker, Sergio Giralt, Marcel R M van den Brink, Eric G Pamer, Ying Taur
Background.: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI following engraftment. Methods.: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S rRNA genes were sequenced and analyzed from each sample...
January 30, 2017: Journal of Infectious Diseases
Jonathan U Peled, Sean M Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B Slingerland, Katya F Ahr, Kori A Porosnicu Rodriguez, Yusuke Shono, Ann E Slingerland, Melissa D Docampo, Anthony D Sung, Daniela Weber, Amin M Alousi, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Ying Taur, Eric G Pamer, Robert R Jenq, Marcel R M van den Brink
Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT...
March 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Sandrine Isaac, Jose U Scher, Ana Djukovic, Nuria Jiménez, Dan R Littman, Steven B Abramson, Eric G Pamer, Carles Ubeda
BACKGROUND: Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. METHODS: We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation...
January 2017: Journal of Antimicrobial Chemotherapy
Michael C Abt, Peter T McKenney, Eric G Pamer
Clostridium difficile is a major cause of intestinal infection and diarrhoea in individuals following antibiotic treatment. Recent studies have begun to elucidate the mechanisms that induce spore formation and germination and have determined the roles of C. difficile toxins in disease pathogenesis. Exciting progress has also been made in defining the role of the microbiome, specific commensal bacterial species and host immunity in defence against infection with C. difficile. This Review will summarize the recent discoveries and developments in our understanding of C...
October 2016: Nature Reviews. Microbiology
David C Montrose, Xi Kathy Zhou, Erin M McNally, Erika Sue, Rhonda K Yantiss, Steven S Gross, Nitai D Leve, Edward D Karoly, Chen S Suen, Lilan Ling, Robert Benezra, Eric G Pamer, Andrew J Dannenberg
Treatment with celecoxib, a selective COX-2 inhibitor, reduces formation of premalignant adenomatous polyps in the gastrointestinal tracts of humans and mice. In addition to its chemopreventive activity, celecoxib can exhibit antimicrobial activity. Differing bacterial profiles have been found in feces from colon cancer patients compared with those of normal subjects. Moreover, preclinical studies suggest that bacteria can modulate intestinal tumorigenesis by secreting specific metabolites. In the current study, we determined whether celecoxib treatment altered the luminal microbiota and metabolome in association with reducing intestinal polyp burden in mice...
September 2016: Cancer Prevention Research
Brittany B Lewis, Rebecca A Carter, Eric G Pamer
Clostridium difficile is an anaerobic bacterium that causes diarrheal illnesses. Disease onset is linked with exposure to oral antibiotics and consequent depletion of secondary bile acids. Here we investigate the relationship between in vitro secondary bile acid tolerance and in vivo disease scores of diverse C. difficile strains in mice.
October 2016: Anaerobe
Peter T McKenney, Lilan Ling, Guilin Wang, Shrikant Mane, Eric G Pamer
We report the complete genome sequence of a vancomycin-resistant isolate of Enterococcus faecium derived from human feces. The genome comprises one chromosome of 2.9 Mb and three plasmids. The strain harbors a plasmid-borne vanA-type vancomycin resistance locus and is a member of multilocus sequencing type (MLST) cluster ST-17.
May 19, 2016: Genome Announcements
Yusuke Shono, Melissa D Docampo, Jonathan U Peled, Suelen M Perobelli, Enrico Velardi, Jennifer J Tsai, Ann E Slingerland, Odette M Smith, Lauren F Young, Jyotsna Gupta, Sophia R Lieberman, Hillary V Jay, Katya F Ahr, Kori A Porosnicu Rodriguez, Ke Xu, Marco Calarfiore, Hendrik Poeck, Silvia Caballero, Sean M Devlin, Franck Rapaport, Jarrod A Dudakov, Alan M Hanash, Boglarka Gyurkocza, George F Murphy, Camilla Gomes, Chen Liu, Eli L Moss, Shannon B Falconer, Ami S Bhatt, Ying Taur, Eric G Pamer, Marcel R M van den Brink, Robert R Jenq
Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21...
May 18, 2016: Science Translational Medicine
Simone Becattini, Ying Taur, Eric G Pamer
The gut microbiota is a key player in many physiological and pathological processes occurring in humans. Recent investigations suggest that the efficacy of some clinical approaches depends on the action of commensal bacteria. Antibiotics are invaluable weapons to fight infectious diseases. However, by altering the composition and functions of the microbiota, they can also produce long-lasting deleterious effects for the host. The emergence of multidrug-resistant pathogens raises concerns about the common, and at times inappropriate, use of antimicrobial agents...
June 2016: Trends in Molecular Medicine
Eric G Pamer
The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance...
April 29, 2016: Science
Ying Taur, Eric G Pamer
Infections encountered in the cancer setting may arise from intensive cancer treatments or may result from the cancer itself, leading to risk of infections through immune compromise, disruption of anatomic barriers, and exposure to nosocomial (hospital-acquired) pathogens. Consequently, cancer-related infections are unique and epidemiologically distinct from those in other patient populations and may be particularly challenging for clinicians to treat. There is increasing evidence that the microbiome is a crucial factor in the cancer patient's risk for infectious complications...
April 18, 2016: Genome Medicine
Bhavarth S Shukla, Samuel Shelburne, Katherine Reyes, Mini Kamboj, Jessica D Lewis, Sandra L Rincon, Jinnethe Reyes, Lina P Carvajal, Diana Panesso, Costi D Sifri, Marcus J Zervos, Eric G Pamer, Truc T Tran, Javier Adachi, Jose M Munita, Rodrigo Hasbun, Cesar A Arias
BACKGROUND: Daptomycin has become a front-line antibiotic for multidrug-resistant Enterococcus faecium bloodstream infections (BSIs). We previously showed that E. faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the higher end of susceptibility frequently harbor mutations associated with daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting daptomycin MICs of 3-4 µg/mL treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs ≤2 µg/mL...
June 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Huizhong Xiong, James W Keith, Dane W Samilo, Rebecca A Carter, Ingrid M Leiner, Eric G Pamer
Increasing antibiotic resistance among bacterial pathogens has rendered some infections untreatable with available antibiotics. Klebsiella pneumoniae, a bacterial pathogen that has acquired high-level antibiotic resistance, is a common cause of pulmonary infections. Optimal clearance of K. pneumoniae from the host lung requires TNF and IL-17A. Herein, we demonstrate that inflammatory monocytes are rapidly recruited to the lungs of K. pneumoniae-infected mice and produce TNF, which markedly increases the frequency of IL-17-producing innate lymphoid cells...
April 21, 2016: Cell
Corinne Benakis, David Brea, Silvia Caballero, Giuseppe Faraco, Jamie Moore, Michelle Murphy, Giulia Sita, Gianfranco Racchumi, Lilan Ling, Eric G Pamer, Costantino Iadecola, Josef Anrather
Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity...
May 2016: Nature Medicine
Jakob Loschko, Heidi A Schreiber, Gereon J Rieke, Daria Esterházy, Matthew M Meredith, Virginia A Pedicord, Kai-Hui Yao, Silvia Caballero, Eric G Pamer, Daniel Mucida, Michel C Nussenzweig
Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHCII) mouse...
April 4, 2016: Journal of Experimental Medicine
Michael C Abt, Charlie G Buffie, Bože Sušac, Simone Becattini, Rebecca A Carter, Ingrid Leiner, James W Keith, David Artis, Lisa C Osborne, Eric G Pamer
Antibiotic administration can disrupt the intestinal microbiota and down-regulate innate immune defenses, compromising colonization resistance against orally acquired bacterial pathogens. Vancomycin-resistant Enterococcus faecium (VRE), a major cause of antibiotic-resistant infections in hospitalized patients, thrives in the intestine when colonization resistance is compromised, achieving extremely high densities that can lead to bloodstream invasion and sepsis. Viral infections, by mechanisms that remain incompletely defined, can stimulate resistance against invading bacterial pathogens...
February 24, 2016: Science Translational Medicine
Lars F Westblade, Alex van Belkum, Adam Grundhoff, George M Weinstock, Eric G Pamer, Mark J Pallen, W Michael Dunne
Clinicogenomics is the exploitation of genome sequence data for diagnostic, therapeutic, and public health purposes. Central to this field is the high-throughput DNA sequencing of genomes and metagenomes. The role of clinicogenomics in infectious disease diagnostics and public health microbiology was the topic of discussion during a recent symposium (session 161) presented at the 115th general meeting of the American Society for Microbiology that was held in New Orleans, LA. What follows is a collection of the most salient and promising aspects from each presentation at the symposium...
July 2016: Journal of Clinical Microbiology
Alena M Gallegos, Huizhong Xiong, Ingrid M Leiner, Bože Sušac, Michael S Glickman, Eric G Pamer, Jeroen W J van Heijst
The T cell antigen receptor (TCR) is unique in that its affinity for ligand is unknown before encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display very different reactivity to antigen remains unclear. Here we found that activated CD4(+) T cells, at the peak of clonal expansion, persistently downregulated their TCR expression in proportion to the strength of the initial antigen recognition. This programmed response increased the threshold for cytokine production and recall proliferation in a clone-specific manner and ultimately excluded clones with the highest antigen reactivity...
April 2016: Nature Immunology
Bianca Harris, Sejal M Morjaria, Eric R Littmann, Alexander I Geyer, Diane E Stover, Juliet N Barker, Sergio A Giralt, Ying Taur, Eric G Pamer
RATIONALE: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown. OBJECTIVES: To investigate whether changes in gut microbiota are associated with PCs after HCT. METHODS: A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota...
August 15, 2016: American Journal of Respiratory and Critical Care Medicine
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