Bioprospecting of Uncultured Microorganisms: The Dawning of Antibiotic Discovery

Abstract

Antibiotics are of great benefit for human health such as using in pathogenic infection, organ transplantation, cancer treatment and cholesterol control [1]. But a huge threat of global public health caused by multi-drug-resistance pathogens (e.g., gram-positive methicillin and vancomycin resistant Staphylococcus aureus and New Delhi metallo-beta-lactamase 1 gram-negative bacteria) has emerged extensively [2]. Despite this threat has ever-increasing public awareness regarding “superbug” infections, treatment options, unfortunately, continued to be limited [3]. The discovery of new antibiotics is one of direct action on the treat of drug resistant pathogenic infections for avoiding an epidemic [2]. However, the pace of antibiotic discovery and development with unique scaffold is dramatically declining after the past 60 years of intensive screening [4], especially the collapse of the antibiotic discovery pipeline that the last new class of antibiotics daptomycin discovered in 1987 has been successfully developed into a clinical therapeutic [5]. Currently, all microorganism derived commercial antibiotics come from cultivated species, especially five phyla Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, and Proteobacteria that represent 95% of antibiotic-producing microbes [6]. Because uncultured microorganisms are approximately 99% of microbial species, a recent trend in antibiotic discovery from natural sources emphasizes the investigation of uncultured microorganisms (do not grow under laboratory conditions) to meet the urgent demand for novel drug.