- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Microscopic Colitis
- Bacteriophages and microbial interactions
- Epigenetics and DNA Methylation
- Microbial infections and disease research
- Genomics and Phylogenetic Studies
- Gastrointestinal motility and disorders
- Diet and metabolism studies
- Tryptophan and brain disorders
- Nosocomial Infections in ICU
- Bacterial Genetics and Biotechnology
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Evolution and Genetic Dynamics
- Streptococcal Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Indigenous Studies and Ecology
- Urinary Tract Infections Management
- Metabolomics and Mass Spectrometry Studies
- Probiotics and Fermented Foods
- Viral Infections and Vectors
- Molecular Biology Techniques and Applications
- Bacterial Identification and Susceptibility Testing
- Antibiotic Resistance in Bacteria
United States Food and Drug Administration
2017-2025
Center for Devices and Radiological Health
2023-2025
Food and Drug Administration
2023-2024
Center for Biologics Evaluation and Research
2017-2024
University of Michigan
2012-2022
Loyola University Chicago
2009-2018
Ann Arbor Center for Independent Living
2012
Michigan United
2012
Harvard University
2011
Microbial communities carry out the majority of biochemical activity on planet, and they play integral roles in processes including metabolism immune homeostasis human microbiome. Shotgun sequencing such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but resulting data typically comprise short reads hundreds different organisms are at best challenging assemble comparably single-organism genomes. Here, we describe an alternative...
Antibiotic usage is the most commonly cited risk factor for hospital-acquired Clostridium difficile infections (CDI). The increased due to disruption of indigenous microbiome and a subsequent decrease in colonization resistance by perturbed bacterial community; however, specific changes that lead are poorly understood. We developed statistical models incorporated data with clinical demographic better understand why individuals develop CDI. 16S rRNA genes were sequenced from feces 338...
ABSTRACT Perturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile . Although C. infection is commonly associated with antibiotic use, precise alterations this function are unknown. We used variety perturbations generate diverse array structures, which were then challenged spores. Across these treatments we observed that was never attributable single organism, but rather it multiple members interacting...
Abstract Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of immune response on clinical effectiveness. Here, we develop mouse model assess phage treatment using cocktail five phages from Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage significantly reduces fecal bacterial loads Enterococcus. We also characterize responses elicited following administration...
Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed data from 2,440 European African ancestry as part the National Heart, Lung, Blood Institute's Exome Project, aim which to discover novel genes mechanisms that contribute heart, lung blood disorders.Each was sequenced mean coverage 116×, allowing detailed inferences about population genomic both common rare coding variation.We...
Ecologists hypothesize that community structure and stability affect productivity, sensitivity to invasion extinction, resilience resistance perturbations. Viewed in the context of gut microbiome, is important for understanding effects antibiotics, diet change other perturbations on host health colonization resistance. Here we describe dynamics a self-contained community, murine microbiome. Using 16S rRNA gene sequencing fecal samples collected daily from individual mice, characterized...
Enterococcus faecalis is a human intestinal pathobiont with intrinsic and acquired resistance to many antibiotics, including vancomycin. Nature provides diverse virtually untapped repertoire of bacterial viruses, or bacteriophages (phages), that could be harnessed combat multidrug-resistant enterococcal infections. Bacterial phage represents potential barrier the implementation therapy, emphasizing importance investigating molecular mechanisms underlying emergence resistance. Using cohort 19...
Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that the leading cause of nosocomial bacterial infection globally. C. (CDI) typically occurs after ingestion infectious spores by a patient has been treated with broad-spectrum antibiotics. While CDI toxin-mediated disease, transmission and pathogenesis are dependent on ability to produce viable spores. These must become metabolically active (germinate) in order disease. spore germination when encounter bile salts...
Clostridioides difficile colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict guide treatment decisions are based on clinical factors C. characteristics.
Using populations of two sympatric Peromyscus species, we characterized the importance host physiology, environment, diet, and other factors in shaping structure dynamics their gut microbiota. We performed a capture-mark-release experiment which obtained 16S rRNA gene sequence data from 49 animals at multiple time points. In addition, 18S sequencing same samples to characterize diet each individual. Our analysis could not distinguish between species on basis structures microbiotas. However,...
Clostridium difficile is a Gram-positive obligate anaerobe that forms spores in order to survive for long periods the unfavorable environment outside host. C. leading cause of nosocomial infectious diarrhea worldwide. infection (CDI) arises after patient treated with broad-spectrum antibiotics ingests spores. The first step pathogenesis metabolic reactivation dormant within gastrointestinal (GI) tract through process known as germination. In this work, we aim elucidate specific conditions...
Abstract Molecular assays are critical tools for the diagnosis of infectious diseases. These have been extremely valuable during COVID pandemic, used to guide both patient management and infection control strategies. Sustained transmission unhindered proliferation virus pandemic resulted in many variants with unique mutations. Some these mutations could lead signature erosion, where tests developed using genetic sequence an earlier version pathogen may produce false negative results when...
The community of microorganisms, or microbiota, in our intestines prevents pathogens like C. difficile from colonizing and causing infection. However, antibiotics can disturb the gut which allows to colonize. infections (CDI) are primarily treated with antibiotics, frequently leads recurrent because microbiota has not yet returned a resistant state.
Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) host microbiome. Here we were interested determining whether absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) MR1-/- mice treated with antibiotics then infected Cd spores. Surprisingly, exhibited colonization....
Abstract Background When introduced to novel environments, the ability for a species survive and rapidly proliferate corresponds with its adaptive potential. Of many factors that can yield an environment inhospitable foreign species, phenotypic response variation in thermal climate has been observed within wide variety of species. Experimental evolution studies using bacteriophage model systems have able elucidate mutations, which may correspond phage modest increases/decreases temperature...
Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection virus genome compatibility with potential hosts, appropriate gene regulation expression necessary a successful infection. While bioinformatic studies have shown correlations between codon usage in host genomes, the selective factors by which this evolves remain matter conjecture. Engineered to include codons lesser and/or tRNA abundance within host, three...
Abstract Clostridium difficile (Cd) is a leading cause of nosocomial infection. Cd infection (CDI) typically occurs following antibiotic usage, which perturbs the gut microbiota leaving host susceptible to colonization. Mucosa-associated invariant T cells (MAIT) recognize intermediates riboflavin biosynthesis presented on MR1, an MHC-I like related molecule. MAIT cell development dependent microbiome. are found in high numbers at mucosal sites and beneficial combatting various pulmonary...
<title>Abstract</title> Molecular assays are critical tools for the diagnosis of infectious diseases. These have been extremely valuable during COVID pandemic, used to guide both patient management and infection control strategies. Sustained transmission unhindered proliferation virus pandemic resulted in many variants with unique mutations. Some these mutations could lead signature erosion, where tests developed using genetic sequence an earlier version pathogen may produce false negative...
Abstract The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, creatinine levels as well C. ribotype and toxin genes have been associated with disease severity. However, it is unclear whether there an association between members gut microbiota known to interact during infection. Perturbations are necessary for colonize gut. can inhibit colonization through bile acid metabolism, nutrient consumption bacteriocin...
Abstract Enterococcus faecalis is a human intestinal pathobiont with intrinsic and acquired resistance to many antibiotics, including vancomycin. Nature provides diverse virtually untapped repertoire of bacterial viruses, or bacteriophages (phages), that could be harnessed combat multi-drug resistant enterococcal infections. Bacterial phage represents potential barrier the implementation therapy, emphasizing importance investigating molecular mechanisms underlying emergence resistance. Using...