E. Chain

Bio: E. Chain is an academic researcher from University of Oxford. The author has contributed to research in topics: Penicillin & Antibiotics. The author has an hindex of 11, co-authored 16 publications receiving 2518 citations.

An Enzyme from Bacteria able to Destroy Penicillin

Abstract: FLEMING1 noted that the growth of B. coli and a number of other bacteria belonging to the colityphoid group was not inhibited by penicillin. This observation has been confirmed. Further work has been done to find the cause of the resistance of these organisms to the action of penicillin.

THE CLASSIC: penicillin as a chemotherapeutic agent. 1940.

Abstract: Ernest Boris Chain (Fig. I ) was born and educated in Berlin. He obtained his doctor of philosophy from Friedrich-Whilhelms University in 1933, majoring in chemistry and physiology. Initially, he worked as a biochemist in the Institute for Pathology at the CharitC Hospital in Berlin, but in 1933, because of the rise of the Nazi regime, he moved to England, where he became a British citizen. For two years, he worked in the School of Biochemistry at Cambridge, and then moved to the Sir William Dunn School of Pathology at Oxford, where he worked with Professor Howard Florey. Florey called his attention to the paper published by Alexander Reming in 1928 which reported the observation that the mould, Pt.nicillium notatum, produced a bacteriainhibiting substance that Fleming had not been able to isolate. In collaboration with Florey, Chain began the study of antibacterial substances produced by microorganisms, which culminated with the discovery of the therapeutic properties of pure penicillin. This work was done under severe financial hardship because of limited support by the British Medical Research Council. Although Chain was able to produce small amounts of penicillin, he lacked the enormous resources that permitted laboratories in the United States to rapidly produce commercial quantities of the material. In 1945, Chain, Florey, and Fleming shared the Nobel Prize for “the discovery of penicillin and its curative effect in various infectious diseases.” Unable to get the research support that he believed he deserved, Chain moved to Rome where he organized a Department of Biochemistry at the State Institute of Health. At the International Centre for Chemical Microbiology, he finally had the facilities he needed for continuing his work. In 1964, Chain returned to London to the Imperial College where a well-funded position had been created for him. The last years of his life were filled with additional honors, including a knighthood in 1969. The following paper, published in 1940, was the first to establish that penicillin was effective against bacteria in v ivo as well as in vitru, and opened up a new era in the treatment of bacterial infections.

Origins and Evolution of Antibiotic Resistance

Abstract: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

Antibiotic resistance—the need for global solutions

Abstract: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

Molecular mechanisms of antibiotic resistance.

Abstract: Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.

Extended-Spectrum β-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat

Abstract: β-Lactamases continue to be the leading cause of resistance to β-lactam antibiotics among gram-negative bacteria. In recent years there has been an increased incidence and prevalence of extended-spectrum β-lactamases (ESBLs), enzymes that hydrolyze and cause resistance to oxyimino-cephalosporins and aztreonam. The majority of ESBLs are derived from the widespread broad-spectrum β-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including the CTX-M and OXA-type enzymes as well as novel, unrelated β-lactamases. Several different methods for the detection of ESBLs in clinical isolates have been suggested. While each of the tests has merit, none of the tests is able to detect all of the ESBLs encountered. ESBLs have become widespread throughout the world and are now found in a significant percentage of Escherichia coli and Klebsiella pneumoniae strains in certain countries. They have also been found in other Enterobacteriaceae strains and Pseudomonas aeruginosa. Strains expressing these β-lactamases will present a host of therapeutic challenges as we head into the 21st century.

Drug Discovery: A Historical Perspective

Abstract: Driven by chemistry but increasingly guided by pharmacology and the clinical sciences, drug research has contributed more to the progress of medicine during the past century than any other scientific factor. The advent of molecular biology and, in particular, of genomic sciences is having a deep impact on drug discovery. Recombinant proteins and monoclonal antibodies have greatly enriched our therapeutic armamentarium. Genome sciences, combined with bioinformatic tools, allow us to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future medicines, thereby increasing the number of treatment options. The dramatic increase in the complexity of drug research is enforcing changes in the institutional basis of this interdisciplinary endeavor. The biotech industry is establishing itself as the discovery arm of the pharmaceutical industry. In bridging the gap between academia and large pharmaceutical companies, the biotech firms have been effective instruments of technology transfer.