NVB302

There has been an alarming rise in antibacterial resistant infections in recent years due to the widespread use of antibiotics, and there is a dire need for the development of new antibiotics utilizing novel modes of action. Lantibiotics are promising candidates to engage in the fight against resistant strains of bacteria due to their unique modes of action, including interference with cell wall synthesis by binding to lipid II and creating pores in bacterial membranes. In this study, we use atomic-scale molecular dynamics computational studies to compare both the lipid II binding ability and the membrane interactions of five lanthipeptides that are commonly used in antimicrobial research: nisin, Mutacin 1140 (MU1140), gallidermin, NVB302, and NAI107...

Clostridium difficile is a major cause of healthcare-associated diarrhea linked to the misuse of antimicrobials and the corresponding deleterious impact they have on the protective microbiota of the gut. Resistance to agents used to treat C. difficile including metronizadole and vancomycin has been reported highlighting the need for novel agents. Lantibiotics represent a novel class of agents that many studies have highlighted as effective against C. difficile. Areas covered: In this review lantibiotics including nisin, actagardine, mersacidin, NAI-107 and MU-1140 that exhibit good activity against C...

The current picture of Clostridium difficile infection (CDI) is alarming with a mortality rate ranging between 3% and 15% and a CDI recurrence rate ranging from 12% to 40%. Despite the great efforts made over the past 10 years to face the CDI burden, there are still gray areas in our knowledge on CDI management. The traditional anti-CDI antimicrobials are not always adequate in addressing the current needs in CDI management. The aim of our review is to give an update on novel antimicrobials for the treatment of CDI, considering the currently available evidences on their efficacy, safety, molecular mechanism of action, and their probability to be successfully introduced into the clinical practice in the near future...

The effectiveness of lantibiotics against MDR pathogens and the progression of agents MU1140, NAI-107, NVB302 and duramycin into pre-clinical and clinical trials have highlighted their potential in the fight against bacterial resistance. The number of known lantibiotics and knowledge of their biosynthetic pathways has increased in recent years due to higher quality genomic data being delivered by next generation sequencing technologies combined with the development of specific genome mining tools, enabling the prediction of lantibiotic clusters...

The increasing resistance of bacteria to conventional antimicrobial therapy within both the nosocomial and community environment has enforced the urgent requirement for the discovery of novel agents. This has stimulated increased research efforts within the field of lantibiotic discovery. Lantibiotics are ribosomally synthesised, post-translationally modified antimicrobial peptides that exhibit antimicrobial activity against a range of multi-drug-resistant (MDR) bacteria. The success of these agents as a novel treatment of MDR infections is exemplified by: the clinical development of MU1140 (mutacin 1140) and NAI-107 (microbisporicin), which are in late pre-clinical trials against gram-positive bacteria; NVB302 that has completed Phase I clinical trials for the treatment of Clostridium difficile infections and; duramycin that has completed Phase II clinical trials in the treatment of cystic fibrosis...

OBJECTIVES: First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model. METHODS: We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C...

IMPORTANCE OF THE FIELD: Clostridium difficile infection (CDI) is associated with consumption of antibiotics which disrupt the normal microbial flora of the gut, allowing C. difficile to establish itself and produce disease. Currently, only vancomycin or metronidazole are recommended for treatment and many patients suffer from relapse on infection. Hence, there is a need for new treatment options. AREAS COVERED IN THIS REVIEW: This review evaluates five agents in development where the focus is on treatment of CDI...