Rate of Discovery of New Drugs Essay

Over the years, the rate of discovery of new drugs has declined significantly, leading to an urge to explore alternative environmental sources apart from the soil, for novel antibiotics. In this study, water samples were collected from different places around Bath and they were screened for antibacterial activity against six test bacteria. Rate of Discovery of New Drugs Essay A total of 106 isolates were isolated and tested against methicillin-sensitive Staphylococcus aureus (MSSA) to confirm their antagonistic activity. 34 isolates showed promising inhibition and were further tested against bacteria which included MSSA, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium (E. faecium), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) through perpendicular streak test. The supernatant of the isolates was also extracted by centrifugation and assayed for its antibacterial activity. For E. coli-inhibiting isolates, further tests against strains of E. coli with different antibiotic resistance were performed to identify the types of antibiotics produced. 11 active isolates were effective against both Gram-positive and Gram-negative bacteria in the perpendicular streak test. The supernatant of the isolates exhibited minimal antibacterial activity. Following the results of 16S rRNA sequencing, two active isolates belonged to Pseudomonas species while the other three isolates were classified as Bacillus species. Isolate 107 was identified as Bacillus pumilus and it demonstrated the strongest inhibition against MSSA, MRSA, E. faecium and E. coli with a zone of inhibition of 20.8mm, 24.3mm, 16.2mm and 13.6mm respectively. Moreover, isolates 18 and 107 both had strong activity against all strains of E. coli tested, while isolate 71 was only active against four strains of E. coli tested, suggesting that one of the antibiotics produced may be kanamycin. Our findings indicate that aquatic environment is a potent source for the isolation of bioactive microorganism potential for the production of antibacterial compounds.Rate of Discovery of New Drugs Essay

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1. Introduction

Microbes play an essential role in the production of antibiotics, antifungal as well as antiviral infections and this role is expanding each day (1). Owing to their ability to produce useful secondary metabolites, microbes have contributed greatly in the development of pharmaceutical industry and the control of many medical conditions as they are now widely used as antitumour drugs, immunosuppressants, enzyme inhibitors, and in many other applications (1). Back in 1928, Alexander Fleming found a compound produced by a mould, which was later identified as Penicillium notatum, had the capability of killing the bacterium Staphylococcus aureus in his laboratory. The active compound was known as penicillin, a beta-lactam antibiotic, and it was used massively as a potent antimicrobial drug during World War II (1). This discovery has marked the beginning of the microbial drug era as many useful antibiotics have since been isolated from soil bacteria, for instance, streptomycin, chloramphenicol, and tetracycline (2). These antibiotics produced have had remarkable biological activities to human beings, to illustrate, streptomycin was the first active drug against tuberculosis whereas chloramphenicol was the drug of choice for typhoid fever (3-5).

The soil is incontestably a rich reservoir that allows the screening of drug compounds as it can harbour an enormous number of soil inhabitants, such as bacteria, fungi, algae, protozoa, insects, and other more complex living organisms (6). Many soil organisms have the ability to produce secondary metabolites which enable them to inhibit the growth of other microorganisms in the same niche in order to compete for survival (7). Over the past decades, a significant amount of bioactive compounds have been discovered from the terrestrial environment (3).Rate of Discovery of New Drugs Essay The majority of the useful soil microorganisms belong to the genera Penicillium, Streptomyces, Cephalosporium, Micromonospora and Bacillus, and they are still being studied continuously (8). Bacillus is found abundantly in the soil environment and it is known to produce antibiotic like bacitracin, pumulin and gramicidin which are active against Gram-positive bacteria, and polymyxin, colistin and circulin which are effective against Gram-negative bacteria, demonstrating a vast range of antimicrobial activity (9; 10). Furthermore, more than 60% of antimicrobial agents used in human and animals were originated from the genus Streptomyces, some of which are chloramphenicol, erythromycin, and tetracycline, which have a broad spectrum of activity (5; 9).

In the recent years, the search for antibiotics has plateaued whereby limited new antibacterial drugs are being introduced to the market, posing a challenge to the healthcare sector. The rate of discovery of new compounds has declined and the scientists are facing a bottleneck where the same known antimicrobial compounds have been isolated over the past few years (11). Nowadays, antibiotics are widely used therapeutically and prophylactically in the healthcare setting for human, animals and agricultural purposes. They are commercially exploited and the overconsumption of these compounds has brought about a rapid evolution in microorganisms where resistance to the antibiotics is spreading dramatically. Furthermore, the crisis of multidrug resistance is expanding uncontrollably, leading to a consistent demand for more effective and useful antibacterial medicines. Staphylococcus aureus, Pseudomonas sp., Klebsiella sp., and Enterococcus sp. are examples of common nosocomial bacteria and they often cause a serious problem to hospitalised patients (1). The development of resistance of these pathogens to currently available antibiotics, both natural and synthetic classes of antibiotics, has rendered many of the standard drugs ineffective (12).Rate of Discovery of New Drugs Essay

In view of the scarcity of new antimicrobial medications being found from terrestrial environment, there is an urge to explore different environmental sources. The marine environment consists of a wide diversity of microorganisms, and thus the discovery of many medically useful compounds. The antivirals acyclovir and cytarabine used for herpes virus and non-Hodgkin’s lymphoma respectively were originally isolated from marine sponges, showing the potential of marine life as a novel source of medicines (1). As reported in a study conducted in South East coast of India, organisms originated from the genera Vibrio, Pseudomonas, Marinobacter and Bacillus have been isolated and proven to exhibit antimicrobial activity, where the isolate belonged to Bacillus species had the highest activity against Bacillus subtilis, E. coli and C. albicans (13). Besides that, aquatic actinomycetes have also been reported to produce bioactive compounds with potential clinical uses such as salinosporamide-A (from Salinispora sp.), marinopyrroles (from Streptomyces sp.) and marinobactin (from Marinobacter sp.) (14-16).Rate of Discovery of New Drugs Essay Antibacterial actinomycetes have been successfully isolated from Lake Tana, Ethiopia, of which 13 isolates showed antibacterial ability against at least one of the tested bacteria, such as K. pneumoniae, S. aureus, P. aeruginosa and E. coli (17). Similarly, a study conducted in Ghana has isolated 27 antibiotic-producing microorganisms from marine and freshwater sources and it has been found that one of the active isolates produced metabolites with a broad antibacterial activity against both tested Gram-positive and Gram-negative bacteria (18).

Although it is apparent that the ocean is a boundless source for novel antibacterial compounds, the water sources remain underexplored and unexploited. The aim of this study was to isolate antibiotic-producing microorganisms from the aquatic environment around Bath area and to determine their antibacterial activity against six test bacteria, three of which belonged to Gram-positive bacteria and the other three were Gram-negative bacteria.Rate of Discovery of New Drugs Essay

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