Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial.

Background: The rate of antibiotic resistance continues to grow, outpacing small-molecule-drug development efforts. Novel therapies are needed to combat this growing threat, particularly for the treatment of urinary tract infections (UTIs), which are one of the largest contributors to antibiotic use and associated antibiotic resistance. LBP-EC01 is a novel, genetically enhanced, six-bacteriophage cocktail developed by Locus Biosciences (Morrisville, NC, USA) to address UTIs caused by Escherichia coli, regardless of antibiotic resistance status.

Validation of Commonly Used Antimicrobial Interventions on Bob Veal Carcasses for Reducing Shiga Toxin-Producing Escherichia coli Surrogate Populations.

Abstract: Ruminants are natural reservoirs of Shiga toxin-producing Escherichia coli (STEC), and the STEC can be easily transferred to carcasses during the conversion of animals to meat. Three experiments were conducted to validate the efficacy of lactic acid (LA; 4%), peroxyacetic acid (PAA; 300 ppm), and hot water (HW; 80°C) for their individual or combined abilities to reduce STEC surrogates on bob veal carcasses pre- and postchill and through fabrication. In experiment 1, hot carcasses (n = 9) were inoculated with a five-strain cocktail (ca.

Texture and quality of chicken sausage formulated with woody breast meat.

Woody breast (WB) myopathy is a quality defect, afflicting a large portion of commercial broilers to some degree. The WB myopathy is commonly attributed to rapid bird growth and characterized by excessive fibrosis within the pectoralis major, which is thought to cause the palpably hardened texture observed in the afflicted breast meat. These phenotypically tough breast fillets are not marketed for traditional intact muscle products owing to poor quality and eating experience.

Warm-season annual forages in forage-finishing beef systems: II. Animal performance and carcass characteristics.

More information on expected animal performance and carcass traits of forage-finished steers grazing warm-season annual forages is needed. To achieve this objective, a grazing trial was conducted in 2014, 2015, and 2016 (70, 63, and 56 d, respectively), with variation in length of grazing based on forage availability. Sixteen pastures (0.

Warm-season annual forages in forage-finishing beef systems: I. Forage yield and quality.

The demand for a year-round supply of fresh, locally grown, forage-finished beef products has created a need for forage-finishing strategies during the summer months in the southeast. A 3-yr study was conducted to evaluate four warm-season annual forages in a southeastern forage-finishing beef production system. Treatments were four forage species and included brown-midrib sorghum × sudangrass ( var.

Validation of Antimicrobial Interventions for Reducing Shiga Toxin-Producing Escherichia coli Surrogate Populations during Goat Slaughter and Carcass Chilling.

Demand and consumption of goat meat is increasing in the United States due to an increase in ethnic populations that prefer goat meat. As ruminant animals, goats are known reservoirs for Shiga toxin-producing Escherichia coli (STEC) and proper handling, especially during slaughter, is imperative to reduce the likelihood of carcass and meat contamination. However, the majority of antimicrobial intervention studies during the slaughter of ruminant species have focused on beef, highlighting the need for validation studies targeting small ruminants, such as goats, during slaughter and chilling procedures.

Cyclic Diguanylate Regulates Virulence Factor Genes via Multiple Riboswitches in .

The intracellular signaling molecule cyclic diguanylate (c-di-GMP) regulates many processes in bacteria, with a central role in controlling the switch between motile and nonmotile lifestyles. Recent work has shown that in (also called ), c-di-GMP regulates swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we determined the transcriptional regulon of c-di-GMP in employing overexpression of a diguanylate cyclase gene to artificially manipulate intracellular c-di-GMP.

Type IV Pili Promote Clostridium difficile Adherence and Persistence in a Mouse Model of Infection.

Cyclic diguanylate (c-di-GMP) is a second messenger that regulates the transition from motile to sessile lifestyles in numerous bacteria and controls virulence factor production in a variety of pathogens. In , c-di-GMP negatively regulates flagellum biosynthesis and swimming motility and promotes the production of type IV pili (TFP), biofilm formation, and surface motility Flagella have been identified as colonization factors in , but the role of TFP in adherence to host cells and in colonization of the mammalian gut is unknown. Here we show that c-di-GMP promotes adherence to epithelial cells , which can be partly attributed to the loss of flagella.

A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase.

The signaling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen , c-di-GMP inhibits flagellar motility and toxin production and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases (PDEs).

Regulation of Type IV Pili Contributes to Surface Behaviors of Historical and Epidemic Strains of Clostridium difficile.

Unlabelled: The intestinal pathogen Clostridium difficile is an urgent public health threat that causes antibiotic-associated diarrhea and is a leading cause of fatal nosocomial infections in the United States. C. difficile rates of recurrence and mortality have increased in recent years due to the emergence of so-called "hypervirulent" epidemic strains.

A systematic analysis of the in vitro and in vivo functions of the HD-GYP domain proteins of Vibrio cholerae.

Background: The second messenger cyclic diguanylate (c-di-GMP) plays a central role in bacterial adaptation to extracellular stimuli, controlling processes such as motility, biofilm development, cell development and, in some pathogens, virulence. The intracellular level of c-di-GMP is controlled by the complementary activities of diguanylate cyclases containing a GGDEF domain and two classes of c-di-GMP phosphodiesterases containing an EAL or HD-GYP hydrolytic domain. Compared to the GGDEF and EAL domains, the functions of HD-GYP domain family proteins are poorly characterized.

The second messenger cyclic Di-GMP regulates Clostridium difficile toxin production by controlling expression of sigD.

The Gram-positive obligate anaerobe Clostridium difficile causes potentially fatal intestinal diseases. How this organism regulates virulence gene expression is poorly understood. In many bacterial species, the second messenger cyclic di-GMP (c-di-GMP) negatively regulates flagellar motility and, in some cases, virulence.

Cyclic diguanylate inversely regulates motility and aggregation in Clostridium difficile.

Clostridium difficile-associated disease is increasing in incidence and is costly to treat. Our understanding of how this organism senses its entry into the host and adapts for growth in the large bowel is limited. The small-molecule second messenger cyclic diguanylate (c-di-GMP) has been extensively studied in gram-negative bacteria and has been shown to modulate motility, biofilm formation, and other processes in response to environmental signals, yet little is known about the functions of this signaling molecule in gram-positive bacteria or in C.