Screening an Archetypal Collection of Microorganisms for the Presence of Unexplored Antimicrobial Compounds (original) (raw)

Searching for Antimicrobials in the Unlikeliest of Places

The biggest challenge facing the world’s population is the shortage of antimicrobial compounds. This has arisen due to the overprescribing of antibiotics and other antimicrobials; as a consequence of bacterial resistance, arising from evolutionary mechanisms or plasmid transfer, to one or more antimicrobial compound; to add to this the threat of newly emerging pathogens remains ever-present. To address these issues and to outline current research and developments in the search for new antimicrobials, Tim Sandle has written a new paper for the journal Pharmaceutical Microbiology.

A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity

PLoS ONE, 2012

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive highthroughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples.

Targets and assays for discovering novel antibacterial agents

Journal of Biotechnology, 2002

The increasing frequency of nosocomial infections due to multi-resistant pathogens exerts a significant toll and calls for novel and better antibiotics. Different approaches can be used in the search for novel antibiotics acting on drugresistant bacterial pathogens. We present some considerations on valid bacterial targets to be used for searching new antibiotics, and how the information from bacterial genome sequences can assist in choosing the appropriate targets. Other factors to be considered in target selection are the chemical diversity available for screening and its uniqueness. We will conclude discussing our strategy for searching novel antibacterials. This is based on a large collection of microbial extracts as a source of chemical diversity and on the use of specific targets essential for the viability of bacterial pathogens. Two assay strategies have been implemented: a pathway-based assay, where a series of essential bacterial targets is screened in a single assay; and a binding assay, where many targets can be screened individually in the same format. #

Antimicrobial Compounds from Microorganisms

Antibiotics, 2022

Antimicrobial resistance is an exigent public health concern owing to the emergence of novel strains of human resistant pathogens and the concurrent rise in multi-drug resistance. An influx of new antimicrobials is urgently required to improve the treatment outcomes of infectious diseases and save lives. Plant metabolites and bioactive compounds from chemical synthesis have found their efficacy to be dwindling, despite some of them being developed as drugs and used to treat human infections for several decades. Microorganisms are considered untapped reservoirs for promising biomolecules with varying structural and functional antimicrobial activity. The advent of cost-effective and convenient model organisms, state-of-the-art molecular biology, omics technology, and machine learning has enhanced the bioprospecting of novel antimicrobial drugs and the identification of new drug targets. This review summarizes antimicrobial compounds isolated from microorganisms and reports on the mode...

New approaches to antimicrobial discovery: Current development and future prospects

2020

The increasing incidence of infectious diseases has led to a rise in the demand of antimicrobial agents. Owing to the abrupt environmental deterioration, changes in population dynamics, increased human-animal interaction, and abuse of antibiotics, there has been a rise in the cases of bacterial, viral, fungal, and parasitic diseases. These factors have further led to an increase in antimicrobial resistance and, hence, a decrease in the availability of safe and effective antimicrobial agents. There has been a void of nearly three decades in the discovery of any new antimicrobial. The drug discovery and development process involve the identification of the appropriate molecular target, development of an effective inhibitory agent, animal testing, and clinical trials. These steps are completed in 10–12 years making the whole drug development process time-consuming, expensive, and laborious. The advent of Omics sciences has paved the way to make the antimicrobial drug development proces...

A Simple Assay to Screen Antimicrobial Compounds Potentiating the Activity of Current Antibiotics

BioMed Research International, 2013

Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract ofJuglans regiatree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract ofJ. regiabark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria,Salmonella typhior enteropathogenicE. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as con...

Antibacterial Discovery and Development: From Gene to Product and Back

BioMed Research International, 2015

Concern over the reports of antibiotic-resistant bacterial infections in hospitals and in the community has been publicized in the media, accompanied by comments on the risk that we may soon run out of antibiotics as a way to control infectious disease. Infections caused byEnterococcus faecium, Staphylococcus aureus, Klebsiellaspecies,Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and otherEnterobacteriaceaespecies represent a major public health burden. Despite the pharmaceutical sector’s lack of interest in the topic in the last decade, microbial natural products continue to represent one of the most interesting sources for discovering and developing novel antibacterials. Research in microbial natural product screening and development is currently benefiting from progress that has been made in other related fields (microbial ecology, analytical chemistry, genomics, molecular biology, and synthetic biology). In this paper, we review how no...

Microbial drug discovery: 80 years of progress

Journal of Antibiotics, 2009

Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.