Alexander Fleming

Bio: Alexander Fleming is an academic researcher from St Mary's Hospital. The author has contributed to research in topics: Penicillin & Antibiotics. The author has an hindex of 21, co-authored 65 publications receiving 4278 citations.

On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzæ

Abstract: 1. A certain type of penicillium produces in culture a powerful antibacterial substance. The antibacterial power of the culture reaches its maximum in about 7 days at 20o C. and after 10 days diminishes until it has almost disappeared in 4 weeks. 2. The best medium found for the production of the antibacterial substance has been ordinary nutrient broth. 3. The active agent is readily filterable and the name "penicillin" has been given to filtrates of broth cultures of the mould. 4. Penicillin loses most of its power after 10 to 14 days at room temperature but can be preserved longer by neutralization. 5. The active agent is not destroyed by boiling for a few minutes but in alkaline solution boiling for 1 hour markedly reduces the power. Autoclaving for 20 minutes at 115o C. practically destroys it. It is soluble in alcohol but insoluble in ether or chloroform. 6. The action is very marked on the pyogenic cocci and the diphtheria group of bacilli. Many bacteria are quite insensitive, e.g. the coli-typhoid group, the influenza-bacillus group, and the enterococcus. 7. Penicillin is non-toxic to animals in enormous doses and is non-irritant. It doses not interfere with leucocytic function to a greater degree than does ordinary broth. 8. It is suggested that it may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes. 9. The use of penicillin on culture plates renders obvious many bacterial inhibitions which are not very evident in ordinary cultures. 10. Its value as an aid to the isolation of B. influenzae has been demonstrated.

On a Remarkable Bacteriolytic Element Found in Tissues and Secretions

Abstract: In this communication I wish to draw attention to a substance present in the tissues and secretions of the body, which is capable of rapidly dissolving certain bacteria. As this substance has properties akin to those of ferments I have called it a “Lysozyme,” and shall refer to it by this name throughout the communication. The lysozyme was first noticed during some investigations made on a patient suffering from acute coryza. The nasal secretion of this patient was cultivated daily on blood agar plates, and for the first three days of the infection there was no growth, with the exception of an occasional staphylococcus colony. The culture made from the nasal mucus on the fourth day showed in 24 hours a large number of small colonies which, on examination, proved to be large gram-positive cocci arranged irregularly but with a tendency to diplococcal and tetrad formation. It is necessary to give here a very brief description of this microbe as with it most of the experiments described below were done, and it was with it that the phenomena to be described were best manifested. The microbe has not been exactly identified, but for purposes of this communication it may be alluded to as the Micrococcus lysodeikticus .

On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ

Abstract: 1. A certain type of penicillium produces in culture a powerful antibacterial substance. The antibacterial power of the culture reaches its maximum in about 7 days at 20o C. and after 10 days diminishes until it has almost disappeared in 4 weeks. 2. The best medium found for the production of the antibacterial substance has been ordinary nutrient broth. 3. The active agent is readily filterable and the name "penicillin" has been given to filtrates of broth cultures of the mould. 4. Penicillin loses most of its power after 10 to 14 days at room temperature but can be preserved longer by neutralization. 5. The active agent is not destroyed by boiling for a few minutes but in alkaline solution boiling for 1 hour markedly reduces the power. Autoclaving for 20 minutes at 115o C. practically destroys it. It is soluble in alcohol but insoluble in ether or chloroform. 6. The action is very marked on the pyogenic cocci and the diphtheria group of bacilli. Many bacteria are quite insensitive, e.g. the coli-typhoid group, the influenza-bacillus group, and the enterococcus. 7. Penicillin is non-toxic to animals in enormous doses and is non-irritant. It doses not interfere with leucocytic function to a greater degree than does ordinary broth. 8. It is suggested that it may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes. 9. The use of penicillin on culture plates renders obvious many bacterial inhibitions which are not very evident in ordinary cultures. 10. Its value as an aid to the isolation of B. influenzae has been demonstrated.

Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

Abstract: Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.

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.

A new antibiotic kills pathogens without detectable resistance

Abstract: Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

How antibiotics kill bacteria: from targets to networks

Abstract: Antibiotic drug-target interactions, and their respective direct effects, are generally well characterized. By contrast, the bacterial responses to antibiotic drug treatments that contribute to cell death are not as well understood and have proven to be complex as they involve many genetic and biochemical pathways. In this Review, we discuss the multilayered effects of drug-target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing. We also discuss new insights into these mechanisms that have been revealed through the study of biological networks, and describe how these insights, together with related developments in synthetic biology, could be exploited to create new antibacterial therapies.

Wound microbiology and associated approaches to wound management.

Abstract: The majority of dermal wounds are colonized with aerobic and anaerobic microorganisms that originate predominantly from mucosal surfaces such as those of the oral cavity and gut. The role and significance of microorganisms in wound healing has been debated for many years. While some experts consider the microbial density to be critical in predicting wound healing and infection, others consider the types of microorganisms to be of greater importance. However, these and other factors such as microbial synergy, the host immune response, and the quality of tissue must be considered collectively in assessing the probability of infection. Debate also exists regarding the value of wound sampling, the types of wounds that should be sampled, and the sampling technique required to generate the most meaningful data. In the laboratory, consideration must be given to the relevance of culturing polymicrobial specimens, the value in identifying one or more microorganisms, and the microorganisms that should be assayed for antibiotic susceptibility. Although appropriate systemic antibiotics are essential for the treatment of deteriorating, clinically infected wounds, debate exists regarding the relevance and use of antibiotics (systemic or topical) and antiseptics (topical) in the treatment of nonhealing wounds that have no clinical signs of infection. In providing a detailed analysis of wound microbiology, together with current opinion and controversies regarding wound assessment and treatment, this review has attempted to capture and address microbiological aspects that are critical to the successful management of microorganisms in wounds.