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J Appl Microbiol. 2017 Feb 28. doi: 10.1111/jam.13432. [Epub ahead of print]

SYN-004 (ribaxamase), an oral beta-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model.

Author information

1
Synthetic Biologics Inc., Rockville, MD, USA.
2
CosmosID Inc., Rockville, MD, USA.
3
University of Maryland Institute of Advanced Computer Studies, University of Maryland, College Park, MD, USA.

Abstract

AIM:

To evaluate an antibiotic inactivation strategy to protect the gut microbiome from antibiotic-mediated damage.

METHODS AND RESULTS:

SYN-004 (ribaxamase) is an orally delivered beta-lactamase intended to degrade penicillins and cephalosporins within the gastrointestinal tract to protect the microbiome. Pigs (20 kg, n = 10) were treated with ceftriaxone (CRO) (IV, 50 mg kg-1 , SID) for 7 days and a cohort (n = 5) received ribaxamase (PO, 75 mg, QID) for 9 days beginning the day before antibiotic administration. Ceftriaxone serum levels were not statistically different in the antibiotic-alone and antibiotic + ribaxamase groups, indicating ribaxamase did not alter systemic antibiotic levels. Whole-genome metagenomic analyses of pig faecal DNA revealed that CRO caused significant changes to the gut microbiome and an increased frequency of antibiotic resistance genes. With ribaxamase, the gut microbiomes were not significantly different from pretreatment and antibiotic resistance gene frequency was not increased.

CONCLUSION:

Ribaxamase mitigated CRO-mediated gut microbiome dysbiosis and attenuated propagation of the antibiotic resistance genes in pigs.

SIGNIFICANCE AND IMPACT OF THE STUDY:

Damage of the microbiome can lead to overgrowth of pathogenic organisms and antibiotic exposure can promote selection for antibiotic-resistant micro-organisms. Ribaxamase has the potential to become the first therapy designed to protect the gut microbiome from antibiotic-mediated dysbiosis and reduce emergence of antibiotic resistance.

KEYWORDS:

antibiotic; antibiotic resistance; beta-lactamase; dysbiosis; intestinal microbiology; microbiome; pig

PMID:
28245091
DOI:
10.1111/jam.13432

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