Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus.
View Article and Find Full Text PDFThe severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity.
View Article and Find Full Text PDFThe gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing colonization across different community perturbations. However, those bacteria alone have been unable to clear colonization.
View Article and Find Full Text PDFis a human intestinal pathobiont with intrinsic and acquired resistance to many antibiotics, including vancomycin. Nature provides a diverse and virtually untapped repertoire of bacterial viruses, or bacteriophages (phages), that could be harnessed to combat multidrug-resistant enterococcal infections. Bacterial phage resistance represents a potential barrier to the implementation of phage therapy, emphasizing the importance of investigating the molecular mechanisms underlying the emergence of phage resistance.
View Article and Find Full Text PDFis a Gram-positive obligate anaerobe that forms spores in order to survive for long periods in the unfavorable environment outside a host. is the leading cause of nosocomial infectious diarrhea worldwide. infection (CDI) arises after a patient treated with broad-spectrum antibiotics ingests infectious spores.
View Article and Find Full Text PDFViruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture.
View Article and Find Full Text PDFClostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C.
View Article and Find Full Text PDFUnlabelled: Perturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile. Although C. difficile infection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this loss in function are unknown.
View Article and Find Full Text PDFClostridium septicum is an uncommon cause of severe infection. Real-time PCR against the C. septicum-specific alpha-toxin gene (csa) was used to estimate the prevalence of this microbe in human stool from 161 asymptomatic community-dwelling adults and 192 hospitalized patients with diarrhea.
View Article and Find Full Text PDFUsing populations of two sympatric Peromyscus species, we characterized the importance of the host species, physiology, environment, diet, and other factors in shaping the structure and dynamics of their gut microbiota. We performed a capture-mark-release experiment in which we obtained 16S rRNA gene sequence data from 49 animals at multiple time points. In addition, we performed 18S rRNA gene sequencing of the same samples to characterize the diet of each individual.
View Article and Find Full Text PDFAntibiotic usage is the most commonly cited risk factor for hospital-acquired Clostridium difficile infections (CDI). The increased risk is due to disruption of the indigenous microbiome and a subsequent decrease in colonization resistance by the perturbed bacterial community; however, the specific changes in the microbiome that lead to increased risk are poorly understood. We developed statistical models that incorporated microbiome data with clinical and demographic data to better understand why individuals develop CDI.
View Article and Find Full Text PDFMicrobial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome.
View Article and Find Full Text PDFEcologists hypothesize that community structure and stability affect productivity, sensitivity to invasion and extinction, and resilience and resistance to perturbations. Viewed in the context of the gut microbiome, the stability of the gut community is important for understanding the effects of antibiotics, diet change and other perturbations on host health and colonization resistance. Here we describe the dynamics of a self-contained community, the murine gut microbiome.
View Article and Find Full Text PDFBackground: When introduced to novel environments, the ability for a species to survive and rapidly proliferate corresponds with its adaptive potential. Of the many factors that can yield an environment inhospitable to foreign species, phenotypic response to variation in the thermal climate has been observed within a wide variety of species. Experimental evolution studies using bacteriophage model systems have been able to elucidate mutations, which may correspond with the ability of phage to survive modest increases/decreases in the temperature of their environment.
View Article and Find Full Text PDFThe adaption of pathogens to their host(s) is a major factor in the emergence of infectious disease and the persistent survival of many of the infectious diseases within the population. Since many of the smaller viral pathogens are entirely dependent upon host machinery, it has been postulated that they are under selection for a composition similar to that of their host. Analyses of sequence composition have been conducted for numerous small viral species including the Flavivirus genus.
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