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Antibiotic producing bacterium Streptomyces coelicolor
Since the discovery of penicillin by Alexander Fleming in 1928, microorganisms have been the most prolific source of antibiotics. More than 70% of antibiotics currently approved for clinical use are derived from natural products that originate from members of the bacterial genus Streptomyces. Most of these drugs were developed during the “Golden Age” of antibiotic discovery (1940s-1960s) when thousands of microorganisms were screened for their ability to produce antibacterial compounds. This gave the upper hand to humans in the struggle against microbes for survival, for over half a millennium. However, in recent times, the number of new antibiotics has decreased dramatically and multi-drug-resistant "superbugs" have been proliferating at an alarming rate.
Novel effective antibiotic drugs are therefore urgently needed to remain ahead of the game and to avoid a post-antibacterial era where a simple infection could end the life of patients entering the clinic for an ordinary operation.
Over the last ten years, a combination of technological advances, in particular in DNA sequencing/bioinformatics tools, microbial genetic engineering and analytical chemistry, has permitted access to a large untapped source of novel antibiotics by mining the genomes of Streptomyces bacteria. Indeed, the sequencing of hundreds of entire Streptomyces genomes has revealed an unexpectedly large number of systems which, we predict, are used by the bacteria to produce useful new substances.
Our work focuses on the fact that many of these systems for antibiotic production are silent when Streptomyces bacteria are cultivated in the laboratory environment. In nature, antibiotic production is tightly controlled and triggered by specific environmental cues (nutrient scarcity, communication from neighbouring microbes, etc.). By investigating the regulatory mechanisms that control antibiotic production our goal is to engineer deregulated Streptomyces strains that will produce substances that could lead to novel antibiotic drugs.
Such genome mining strategies are expected to lead to the discovery of tens of new compounds with clinical utility in the next decades.
The Penicillium genus of fungus was widely known and described before its medical and economic importance was realized. Even in the field of early germ theory, 19th century researchers such as John Tyndall came perilously close to recognising its properties before Alexander Fleming’s famously contaminated culture in 1928 pointed the way towards modern antiobiotics.
Accident became innovation ten years later at the Sir William Dunn School of Pathology in Oxford. Howard Florey’s research team, including Ernst Chain, Norman Heatley and others, began to examine, assay and (from 1941) administer penicillin, purified from the mould. Their research and technology was taken to the United States of America (Florey’s lab coat was soaked in the mould) where their processing was scaled up to enable the large-scale production of penicillin as part of the Allied war effort. Penicillin and its successor antibiotics, have saved millions of lives since.
Dr Christophe Corre is a University Research Fellow at Department of Chemistry, University of Warwick. His work is on new chemical keys to unlock microbial antibiotics.
The 'historical discovery' section of this article was written by staff at the Royal Society.
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