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Hohmann, Elizabeth

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Hohmann

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Elizabeth

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Hohmann, Elizabeth
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Now showing 1 - 10 of 10
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    Fecal Microbiota Transplant: Benefits and Risks
    (Oxford University Press, 2015) Weil, Ana; Hohmann, Elizabeth
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    Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients
    (Public Library of Science, 2017) Moss, Eli L.; Falconer, Shannon B.; Tkachenko, Ekaterina; Wang, Mingjie; Systrom, Hannah; Mahabamunuge, Jasmin; Relman, David A.; Hohmann, Elizabeth; Bhatt, Ami S.
    Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.
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    1798Oral, Frozen Fecal Microbiota Capsules for Relapsing Clostridium difficile Infection
    (Oxford University Press, 2014) Youngster, Ilan; Russell, George; Pindar, Christina; Sauk, Jenny; Hohmann, Elizabeth
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    Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting
    (Public Library of Science, 2013) Andrews, Jason Randolph; Prajapati, Krishna G.; Eypper, Elizabeth; Shrestha, Poojan; Shakya, Mila; Pathak, Kamal R.; Joshi, Niva; Tiwari, Priyanka; Risal, Manisha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Wen, Shawn; Smith, Amy B.; Maru, Duncan; Basnyat, Buddha; Baker, Stephen; Farrar, Jeremy; Ryan, Edward; Hohmann, Elizabeth; Arjyal, Amit
    Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%–97.0%) and 96.0% (92.7%–98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.
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    Implementation of Electronic Consent at a Biobank: An Opportunity for Precision Medicine Research
    (MDPI, 2016) Boutin, Natalie T.; Mathieu, Kathleen; Hoffnagle, Alison G.; Allen, Nicole L.; Castro, Victor M.; Morash, Megan; O’Rourke, P. Pearl; Hohmann, Elizabeth; Herring, Neil; Bry, Lynn; Slaugenhaupt, Susan; Karlson, Elizabeth; Weiss, Scott; Smoller, Jordan
    The purpose of this study is to characterize the potential benefits and challenges of electronic informed consent (eIC) as a strategy for rapidly expanding the reach of large biobanks while reducing costs and potentially enhancing participant engagement. The Partners HealthCare Biobank (Partners Biobank) implemented eIC tools and processes to complement traditional recruitment strategies in June 2014. Since then, the Partners Biobank has rigorously collected and tracked a variety of metrics relating to this novel recruitment method. From June 2014 through January 2016, the Partners Biobank sent email invitations to 184,387 patients at Massachusetts General Hospital and Brigham and Women’s Hospital. During the same time period, 7078 patients provided their consent via eIC. The rate of consent of emailed patients was 3.5%, and the rate of consent of patients who log into the eIC website at Partners Biobank was 30%. Banking of biospecimens linked to electronic health records has become a critical element of genomic research and a foundation for the NIH’s Precision Medicine Initiative (PMI). eIC is a feasible and potentially game-changing strategy for these large research studies that depend on patient recruitment.
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    Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection
    (BioMed Central, 2016) Youngster, Ilan; Mahabamunuge, Jasmin; Systrom, Hannah K.; Sauk, Jenny; Khalili, Hamed; Levin, Joanne; Kaplan, Jess; Hohmann, Elizabeth
    Background: Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. Methods: We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above. Results: Overall, 180 patients aged 7–95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. Conclusions: We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.
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    Universality of human microbial dynamics
    (Springer Nature, 2016) Bashan, Amir; Gibson, Travis; Friedman, Jonathan; Carey, Vincent; Weiss, Scott; Hohmann, Elizabeth; Liu, Yang-Yu
    Human-associated microbial communities have a crucial role in determining our health and well-being and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles9. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies—the Human Microbiome Project and the Student Microbiome Project—we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.
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    Diagnosis of Influenza from Lower Respiratory Tract Sampling after Negative Upper Respiratory Tract Sampling
    (Landes Bioscience, 2013) Bogoch, Isaac; Andrews, Jason Randolph; Zachary, Kimon; Hohmann, Elizabeth
    In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses of influenza were made solely by lower respiratory sampling in 6.9% of cases, as traditional upper respiratory tract tests were negative, indeterminate or not performed. Clinical features of these cases are presented. Clinicians should consider lower respiratory tract sampling in select cases of influenza-like illness for diagnosis.
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    Analysis of Salmonella enterica Serotype Paratyphi A Gene Expression in the Blood of Bacteremic Patients in Bangladesh
    (Public Library of Science, 2010) Sheikh, Alaullah; Bhuiyan, Md. Saruar; Khanam, Farhana; Bukka, Archana; Kalsy, Anuj; Porwollik, Steffen; Cravioto, Alejandro; Logvinenko, Tanya; McClelland, Michael; Graham, James E.; Qadri, Firdausi; Charles, Richelle; Rollins, Sean McKenzie; Harris, Jason; Brooks, W. Abdullah; Larocque, Regina; Hohmann, Elizabeth; Calderwood, Stephen; Ryan, Edward
    Background: Salmonella enterica serotype Paratyphi A is a human-restricted cause of paratyphoid fever, accounting for up to a fifth of all cases of enteric fever in Asia. Methodology/Principal Findings: In this work, we applied an RNA analysis method, Selective Capture of Transcribed Sequences (SCOTS), and cDNA hybridization-microarray technology to identify S. Paratyphi A transcripts expressed by bacteria in the blood of three patients in Bangladesh. In total, we detected 1,798 S. Paratyphi A mRNAs expressed in the blood of infected humans (43.9% of the ORFeome). Of these, we identified 868 in at least two patients, and 315 in all three patients. S. Paratyphi A transcripts identified in at least two patients encode proteins involved in energy metabolism, nutrient and iron acquisition, vitamin biosynthesis, stress responses, oxidative stress resistance, and pathogenesis. A number of detected transcripts are expressed from PhoP and SlyA-regulated genes associated with intra-macrophage survival, genes contained within Salmonella Pathogenicity Islands (SPIs) 1–4, 6, 10, 13, and 16, as well as RpoS-regulated genes. The largest category of identified transcripts is that of encoding proteins with unknown function. When comparing levels of bacterial mRNA using in vivo samples collected from infected patients to samples from in vitro grown organisms, we found significant differences for 347, 391, and 456 S. Paratyphi A transcripts in each of three individual patients (approximately 9.7% of the ORFeome). Of these, expression of 194 transcripts (4.7% of ORFs) was concordant in two or more patients, and 41 in all patients. Genes encoding these transcripts are contained within SPI-1, 3, 6 and 10, PhoP-regulated genes, involved in energy metabolism, nutrient acquisition, drug resistance, or uncharacterized genes. Using quantitative RT-PCR, we confirmed increased gene expression in vivo for a subset of these genes. Conclusion/Significance: To our knowledge, we describe the first microarray-based transcriptional analysis of a pathogen in the blood of naturally infected humans.
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    Comparative Proteomic Analysis of the PhoP Regulon in Salmonella enterica Serovar Typhi Versus Typhimurium
    (Public Library of Science, 2009) Lebrun, Lauren M.; Sheikh, Alaullah; Logvinenko, Tanya; Tarique, Abdullah; Krastins, Bryan; Qadri, Firdausi; Charles, Richelle; Harris, Jason; Chase, Michael; Larocque, Regina; Rollins, Sean McKenzie; Hohmann, Elizabeth; Rosenberg, Ian Morley; Sarracino, David A.; Calderwood, Stephen; Ryan, Edward
    Background: S. Typhi, a human-restricted Salmonella enterica serovar, causes a systemic intracellular infection in humans (typhoid fever). In comparison, S. Typhimurium causes gastroenteritis in humans, but causes a systemic typhoidal illness in mice. The PhoP regulon is a well studied two component (PhoP/Q) coordinately regulated network of genes whose expression is required for intracellular survival of S. enterica. Methodology/Principal Findings: Using high performance liquid chromatography mass spectrometry (HPLC-MS/MS), we examined the protein expression profiles of three sequenced S. enterica strains: S. Typhimurium LT2, S. Typhi CT18, and S. Typhi Ty2 in PhoP-inducing and non-inducing conditions in vitro and compared these results to profiles of \(phoP^−/Q^−\) mutants derived from S. Typhimurium LT2 and S. Typhi Ty2. Our analysis identified 53 proteins in S. Typhimurium LT2 and 56 proteins in S. Typhi that were regulated in a PhoP-dependent manner. As expected, many proteins identified in S. Typhi demonstrated concordant differential expression with a homologous protein in S. Typhimurium. However, three proteins (HlyE, STY1499, and CdtB) had no homolog in S. Typhimurium. HlyE is a pore-forming toxin. STY1499 encodes a stably expressed protein of unknown function transcribed in the same operon as HlyE. CdtB is a cytolethal distending toxin associated with DNA damage, cell cycle arrest, and cellular distension. Gene expression studies confirmed up-regulation of mRNA of HlyE, STY1499, and CdtB in S. Typhi in PhoP-inducing conditions. Conclusions/Significance: This study is the first protein expression study of the PhoP virulence associated regulon using strains of Salmonella mutant in PhoP, has identified three Typhi-unique proteins (CdtB, HlyE and STY1499) that are not present in the genome of the wide host-range Typhimurium, and includes the first protein expression profiling of a live attenuated bacterial vaccine studied in humans (Ty800).