Fucosylated Molecules Competitively Interfere with Cholera Toxin Binding to Host Cells
February 7, 2018
Amberlyn M. Wands, Jakob Cervin, He Huang, Ye Zhang, Gyusaang Youn, Chad A. Brautigam, Maria Matson Dzebo, Per Björklund, Ville Wallenius, Danielle K. Bright, Clay S. Bennett, Pernilla Wittung-Stafshede, Nicole S. Sampson, Ulf Yrlid, and Jennifer J. Kohler
Predicting Future Antibiotic Susceptibility using Regression-based Methods on Longitudinal Massachusetts Antibiogram Data
January 2018
M. L. Tlachac, Elke Rundensteiner, Kerri Barton, Scott Troppy, Kirthana Beaulac and Shira Doron
Resistance and clonality in Escherichia coli and Klebsiella spp. and relationship with antibiotic consumption in major Lebanese hospitals
December 2017
Ziad Daoud, Elie Salem-Sokhn, Elias Dahdouh, Jihad Irani, Ghassan M. Matar, Shira Doron
Efficient measurement and factorization of high-order drug interactions in Mycobacterium tuberculosis
October 11, 2017
Murat Cokol, Nurdan Kuru, Ece Bicak, Jonah Larkins-Ford and Bree B. Aldridge
The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis
October 3, 2017
Sangun Lee, Melanie Harwood, Don Girouard, Marvin J. Meyers, Mary A. Campbell, Gillian Beamer, Saul Tzipori
Innate Immunity to Intracellular Pathogens: Balancing Microbial Elimination and Inflammation
August 9, 2017
Gabriel Mitchell and Ralph R. Isberg
White Paper: Developing Antimicrobial Drugs for Resistant Pathogens, Narrow-Spectrum Indications, and Unmet Needs.
July 15, 2017
Helen W Boucher, Paul G Ambrose, H F Chambers, Richard H Ebright, Amanda Jezek, Barbara E Murray, Jason G Newland, Belinda Ostrowsky, and John H Rex on behalf of the Infectious Diseases Society of America
Interplay Between Antibiotic Resistance and Virulence During Disease Promoted by Multidrug-Resistant Bacteria.
February, 2017
Diseases caused by antibiotic-resistant bacteria in hospitals are the outcome of complex relationships between several dynamic factors, including bacterial pathogenicity, the fitness costs of resistance in the human host, and selective forces resulting from interventions such as antibiotic therapy. The emergence and fate of mutations that drive antibiotic resistance are governed by these interactions. In this review, we will examine how different forms of antibiotic resistance modulate bacterial fitness and virulence potential, thus influencing the ability of pathogens to evolve in the context of nosocomial infections. We will focus on 3 important multidrug-resistant pathogens that are notoriously problematic in hospitals: Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. An understanding of how antibiotic resistance mutations shape the pathobiology of multidrug-resistant infections has the potential to drive novel strategies that can control the development and spread of drug resistance.
In Vitro Evaluation of the Activity of Imipenem-Relebactam against 451 Recent Clinical Isolates of Bacteroides Group and Related Species
Sep 23, 2016
We evaluated the in vitro activity of imipenem-relebactam (imipenem-MK7655) against 451 recent clinical isolates within the Bacteroides group and related species. Relebactam did not enhance or inhibit the activity of imipenem against Bacteroides fragilis or other Bacteroides species. No synergistic or antagonistic effect was observed. The MICs of imipenem-relebactam were equal to or within one dilution of the MICs of these isolates to imipenem.
A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection
September 6, 2016
Clostridium difficile infection (CDI), a leading cause of nosocomial infection, is a serious disease in North America, Europe, and Asia. CDI varies greatly from asymptomatic carriage to life-threatening diarrhea, toxic megacolon, and toxemia. The incidence of community-acquired infection has increased due to the emergence of hypervirulent antibiotic-resistant strains. These new strains contribute to the frequent occurrence of disease relapse, complicating treatment, increasing hospital stays, and increasing morbidity and mortality among patients. Therefore, it is critical to develop new therapeutic approaches that bypass the development of antimicrobial resistance and avoid disruption of gut microflora. Here, we describe the construction of a single heteromultimeric VHH-based neutralizing agent (VNA) that targets the two primary virulence factors of Clostridium difficile, toxins A (TcdA) and B (TcdB). Designated VNA2-Tcd, this agent has subnanomolar toxin neutralization potencies for both C. difficile toxins in cell assays. When given systemically by parenteral administration, VNA2-Tcd protected against CDI in gnotobiotic piglets and mice and to a lesser extent in hamsters. Protection from CDI was also observed in gnotobiotic piglets treated by gene therapy with an adenovirus that promoted the expression of VNA2-Tcd.
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