Since the discovery of penicillin by Alexander Fleming, antibiotics have played a major role in human industrialized societies, limiting the spread of infectious disease and saving millions of lives. However, Fleming himself advised caution, noting in his 1945 Nobel Prize acceptance speech "There is the danger, that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant". As Fleming predicted, an increasing number of multi-drug resistant pathogenic bacteria have precipitated an antibiotics crisis, mainly because modern day administration of antibiotics to humans and livestock exerts a strong selective pressure that ultimately causes evolution of resistance in target pathogens and because only few new antibiotics have been approved for clinical use in recent decades. Consequently, we face “superbugs” and “ESKAPE” organisms that are virtually untreatable with the antibiotics currently available.
After the “Golden Age of Antibiotic Discovery”, we have struggled to find effective strategies to combat the declining number of approved antibiotics. Medicinal chemistry at first dominated the field, creating synthetic derivatives of natural scaffolds, and was followed by combinatorial medicinal chemistry and high-throughput biochemical screening campaigns. But despite enormous financial efforts, both from academia and the pharmaceutical industry, we still fail to access new antibiotics at a sufficient pace.
With the emergence of genomics, proteomics, metabolomics, and improved bioinformatics capabilities, we have entered a new era of drug discovery, in which de-replication of natural products is essential. It is often necessary to combine multiple strategies to enhance the probability of finding new chemical entities. Genome sequencing coupled with advanced metabolomics and de-replication strategies have resulted in the discovery of many new compounds. In addition, biosynthetic techniques, including genetic engineering and synthetic biology, offer alternative and complementary approaches to the production of natural products and their analogs.
In this Research Topic, we would like to spotlight research that uses state-of-the-art –omics technologies to investigate microbial interactions as a source of new natural products and potential drug leads. For at least a billion years, natural products and their respective biosynthetic pathways have been in a constant state of evolutionary refinement. The resulting structurally diverse metabolites fulfil a range of specialised functions, including inter and intra-species interactions, modulation of physiological functions, protection against predators, and induction or enhancement of virulence. Many researchers have been attracted to this topic, but we are far from understanding the roles of most small molecules in microbial interactions. We therefore wish to inspire studies that place natural products in a genomic, regulatory, and functional context, allowing general conclusions about their natural functions, as well as their potential as new therapeutics, particularly antibiotics.
A number of recent Research Topics in Frontiers have focused on antibiotic drug discovery, the emergence and spread of multi-drug resistance, and underlying resistance mechanisms, but discussion of natural products discovery in an ecological context has often been lacking. By drawing attention to interdisciplinary research into microbial interactions as a path to new chemical space, we hope to reach a broad audience in diverse areas of natural product discovery. We welcome reviews, perspectives, and original experimental work within the Topic theme.
Since the discovery of penicillin by Alexander Fleming, antibiotics have played a major role in human industrialized societies, limiting the spread of infectious disease and saving millions of lives. However, Fleming himself advised caution, noting in his 1945 Nobel Prize acceptance speech "There is the danger, that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant". As Fleming predicted, an increasing number of multi-drug resistant pathogenic bacteria have precipitated an antibiotics crisis, mainly because modern day administration of antibiotics to humans and livestock exerts a strong selective pressure that ultimately causes evolution of resistance in target pathogens and because only few new antibiotics have been approved for clinical use in recent decades. Consequently, we face “superbugs” and “ESKAPE” organisms that are virtually untreatable with the antibiotics currently available.
After the “Golden Age of Antibiotic Discovery”, we have struggled to find effective strategies to combat the declining number of approved antibiotics. Medicinal chemistry at first dominated the field, creating synthetic derivatives of natural scaffolds, and was followed by combinatorial medicinal chemistry and high-throughput biochemical screening campaigns. But despite enormous financial efforts, both from academia and the pharmaceutical industry, we still fail to access new antibiotics at a sufficient pace.
With the emergence of genomics, proteomics, metabolomics, and improved bioinformatics capabilities, we have entered a new era of drug discovery, in which de-replication of natural products is essential. It is often necessary to combine multiple strategies to enhance the probability of finding new chemical entities. Genome sequencing coupled with advanced metabolomics and de-replication strategies have resulted in the discovery of many new compounds. In addition, biosynthetic techniques, including genetic engineering and synthetic biology, offer alternative and complementary approaches to the production of natural products and their analogs.
In this Research Topic, we would like to spotlight research that uses state-of-the-art –omics technologies to investigate microbial interactions as a source of new natural products and potential drug leads. For at least a billion years, natural products and their respective biosynthetic pathways have been in a constant state of evolutionary refinement. The resulting structurally diverse metabolites fulfil a range of specialised functions, including inter and intra-species interactions, modulation of physiological functions, protection against predators, and induction or enhancement of virulence. Many researchers have been attracted to this topic, but we are far from understanding the roles of most small molecules in microbial interactions. We therefore wish to inspire studies that place natural products in a genomic, regulatory, and functional context, allowing general conclusions about their natural functions, as well as their potential as new therapeutics, particularly antibiotics.
A number of recent Research Topics in Frontiers have focused on antibiotic drug discovery, the emergence and spread of multi-drug resistance, and underlying resistance mechanisms, but discussion of natural products discovery in an ecological context has often been lacking. By drawing attention to interdisciplinary research into microbial interactions as a path to new chemical space, we hope to reach a broad audience in diverse areas of natural product discovery. We welcome reviews, perspectives, and original experimental work within the Topic theme.
