SCOPE AND HISTORY OF MICROBIOLOGY

1. SCOPE AND HISTORY OF MICROBIOLOGY CHAPTER 1

2. Bio 308 General Microbiology Notes and syllabus are on web site: http://bio.as.uky.edu/users/shellys My e-mail: shellys@uky.edu Phone: 859-257-3870 Text Book: Microbiology- Principles and Explorations Jacquelyn G. Black- 7 or 8th edition

3. Chapter 1 Scope and History of Microbiology Microbes have a major impact on human health In 1962, the U.S. Surgeon General, William H. Stewart, stated, “ The war against infectious disease has been won.” In the subsequent decades, emerging diseases and increasing antibiotic resistance have made it clear that in reality not only is the war far from won, its outcome is not longer certain The above (1962) is the basic climate that I started my Ph.D. studies in microbiology

4. 'Golden age' of antibiotics 'set to end‘ Far fewer pharmaceutical companies are working on new antibiotics than in the past. The growing threat of antibiotic resistant organisms is once again in the spotlight. Prof Farrar told BBC Radio 4's Today programme that the golden age of antibiotics could come to an end unless action is taken. Last year she described the growing resistance to antibiotics as a "ticking time bomb", and said the danger should be ranked alongside terrorism on a list of threats to the nation. In 1998 a House of Lords report gave this stark assessment: "Antibiotic resistance threatens mankind with the prospect of a return to the pre-antibiotic era.“Two bacterial infections illustrate the problem. Multi-drug resistant (MDR) tuberculosis is rising steadily worldwide. Another example is the rise in infections from enterobacteriaceae - bugs that live in the gut like E.coli and Klebsiella. They are now the commonest cause of hospital acquired infection and some are becoming resistant to carbapenems, a powerful, last resort group of antibiotics. There has also been an alarming increase in rates of the sexually transmitted disease gonorrhoea, which is becoming more difficult to treat. He said there are just four pharmaceutical companies working on antibiotics now compared to 18 companies 20 years ago.

5. Antibiotics in Animals Tied to Risk of Human Infection A federal analysis of 30 antibiotics used in animal feed found that the majority of them were likely to be contributing to the growing problem of bacterial infections that are resistant to treatment in people, according to documents released Monday by a health advocacy group. The analysis, conducted by the Food and Drug Administration and covering the years 2001 to 2010, was detailed in internal records that the nonprofit group, the Natural Resources Defense Council, obtained through a Freedom of Information Act request and subsequent litigation. In the documents, some of which were reviewed by The New York Times, scientists from the F.D.A. studied 30 penicillin and tetracycline additives in animal feed. They found that 18 of them posed a high risk of exposing humans to antibiotic-resistant bacteria through food. Resistant bacteria make it difficult and sometimes impossible to treat infections with ordinary antibiotics. The scientists did not have enough data to judge the other 12 drugs. At least two million Americans fall sick every year and about 23,000 die from antibiotic-resistant infections, the Centers for Disease Control and Prevention estimates. Representatives of the food industry largely blame hospitals and treatments given to people for the rise of deadly superbugs. But many scientists believe that indiscriminate use of antibiotics in animal feed is a major contributor. Farmers and ranchers feed small amounts of the drugs to animals over their lifetimes to keep them healthy in crowded conditions, causing bacteria to develop a resistance passed on to people through the environment and eating meat from the animals.

6. U.S. Aims to Curb Peril of Antibiotic Resistance WASHINGTON — The Obama administration on Thursday announced measures to tackle the growing threat of antibiotic resistance, outlining a national strategy that includes incentives for the development of new drugs, tighter stewardship of existing ones, and improvements in tracking the use of antibiotics and the microbes that are resistant to them. The actions are the first major White House effort to confront a public health crisis that takes at least 23,000 lives a year, and many experts were pleased that a president had finally focused on the issue. But some said the strategy fell short in not recommending tougher measures against the overuse of antibiotics in agriculture, which, they argue, is a big part of the problem. Researchers have been warning for years that antibiotics — miracle drugs that changed the course of human health in the 20th century — are losing their power because of overuse. Some warn that if the trend is not halted, we could return to the time before antibiotics, when it was common for people to die from ordinary infections and for children not to survive strep throat. Under the order, Mr. Obama created a national task force to be led by the secretaries of health and human services, defense and agriculture, and he required that they deliver a five-year action plan by Feb. 15. He also directed the Department of Health and Human Services to propose regulations requiring hospitals to set up antibiotics stewardship programs. “This represents a major elevation of the issue,” said Dr. Holdren, who talked of the problem as a national security issue. He said the order also established a $20 million prize for the development of a diagnostic test that could be used in hospitals to quickly identify highly resistant bacterial infections.

7. www.bbc.co.uk/guides/z8kccdm Human vs superbug: Too late to turn the tide? Pharmaceutical research hasn't kept up with the growing resistance of bacteria to antibiotics. No new types (classes) of antibiotics have been discovered for 25 years and some strains of bacteria now are unharmed by nearly all the drugs designed to kill them, making infections by these bacteria almost untreatable. Experts have warned we are decades behind in the race against the superbugs. We've already exploited the most obvious naturally occurring antibiotics. So creating new ones requires much more time and ingenuity, but currently there is little financial incentive to do so. Pharmaceutical companies target chronic illnesses to maximise potential profits from new drugs.

8. New Antibiotic Stirs Hope Against Resistant Bacteria JAN. 7, 2015 An unusual method for producing antibiotics may help solve an urgent global problem: the rise in infections that resist treatment with commonly used drugs, and the lack of new antibiotics to replace ones that no longer work. The method, which extracts drugs from bacteria that live in dirt, has yielded a powerful new antibiotic, researchers reported in the journal Nature on Wednesday. The new drug, teixobactin, was tested in mice and easily cured severe infections, with no side effects. Teixobactin has not yet been tested in humans, so its safety and effectiveness are not known. Regarding teixobactin, he said: “It’s at the test-tube and the mouse level, and mice are not men or women, and so moving beyond that is a large step, and many compounds have failed.” He added, “Toxicity is often the Achilles’ heel of drugs.” Drug-resistant bacteria infect at least two million people a year in the United States and kill 23,000, according to the Centers for Disease Control and Prevention. “Drug resistant strains of many diseases were emerging faster than new antibiotics could be made to fight them.” Teixobactin works against bacteria in a group known as “Gram-positive,” but not against microbes that are “Gram-negative,” Teixobactin attacks bacteria by blocking fatty molecules needed to build cell walls, which is different from the way most antibiotics work.

9. Microbes help maintain the balance of nature- mostly microorganisms decompose releasing nitrogen or breaking down industrial wastes or breaking down cellulose in the digestive tract of grazing animals. Microorganisms are important in many human endeavors: Foods(fermentation products (a long list that will be dealt with later in the course), antibiotics, products of genetic engineering, removal of toxic wastesand on and on. In future years many industrial processes carried out by chemical reactions will be done by bacterial (e.g., plastics). In addition, very recent studies suggest that the microflora in the gut, in particular, influences our health and behavior.

10. Roles of Microbes • Pathogens • Food chain • Autotrophs • Decomposers • Digestive • Foods and fermentation • Antibiotics • Biotechnology • Bioremediation • Disease Research

11. Microbe Types • Prokaryotes – 2 Domains/Superkingdoms • Bacteria • Some pathogens • Science of Bacteriology • Archaea • Environmental extremophiles • Novel biochemistry

12. Viruses (Acellular) • Simple structure • Capsid • Nucleic acid • Obligate intracellular growth • Science of Virology • Smaller relatives • Viroids • Prions

13. Germ Theory • Theory definition • Koch • Culture • Postulates • Semmelweiss • Lister

14. Fields of Microbiology • Infection Control • Chemotherapy • Industrial Microbiology • Biotechnology • Biofilms and health

15. THE GERM THEORY OF DISEASE-microorganisms can invade other organisms and cause disease. Because the prevailing theory of the day was spontaneous generation, i.e., that life forms arouse from non-living things, e.g., fruit flies are made from bananas. Thus, it was difficult for people to believe the germ theory. The demonstration by a number of individual that life only come from preexisting life put an end to the idea of spontaneous generation. It is worthwhile mentioning that spontaneous generation, although totally incorrect, follows Occam’s razor ( "All other things being equal, the simplest solution is the best.“).

16. Although Occam’s razor is a good general idea- It only becomes science when it is testable. In addition to testability science is hypothesis driven. A hypothesis is a tentative explanation to account for an observed condition or event. Hence, a testable hypothesis is one for which evidence can be collected to support or refute the hypothesis. In science, a theory is a mathematical or logical explanation, or a testable model of the manner of interaction of a set of naturalphenomena, capable of predicting future occurrences or observations of the same kind, and capable of being tested through experiment or otherwise falsified through empirical observation. It follows from this that for scientists "theory" and "fact" do not necessarily stand in opposition. For example, it is a fact that an apple dropped on earth has been observed to fall towards the center of the planet, and the theories commonly used to describe and explain this behavior are Newton's theory of universal gravitation (see also gravitation), and general relativity. An explanation that cannot be tested is not science.

17. Louis Pasteur, a chemist, is considered as a giant in the history of microbiology. In addition to his contribution to the spontaneous generation/germ theory debate he contributed a great deal to the development of the field of microbiology. • A. Pasteurization of wine so that pure seed cultures could be used in wine production • B. major contribution to the germ theory of disease in demonstrating that microorganisms caused silk worm disease and Anthrax.. • C. He developed a rabies vaccine (and thereby demonstrated the value of vaccination) and on and on. • It is worthwhile mentioning that Pasteur popularized the correct explanation of many things he was not the initial author of any of the above ideas. • Robert Koch – developed a method for pure culture. Probably as important as his work on tuberculosis, for which he was awarded a Nobel Prize (1905), are Koch's postulates, which say that to establish that an organism is the cause of a disease, it must be: • found in all cases of the disease examined, 2) prepared and maintained in a pure culture capable of producing the original infection, 3) even after several generations in culture be retrievable from an inoculated animal and cultured again. We will visit Koch’s postulates again when we discuss disease. • The finding that there are asymptomatic carriers of typhoid and cholera made Koch modify the third part of his postulates to be less dogmatic.

18. WORK TOWARD CONTROLLING INFECTIONS 1. IgnazSemmelwis (Devils, Doctors and Drugs is a very interesting biography of Semmelweis). He was an obstetrician who pioneered aseptic technique and died of sepsis. His trials at trying to popularize the idea that aseptic technique could defeat childbed fever (streptococcal infection that accompanies childbirth) is a classic example of the difficulty in trying to establish a new principle in the medical community. 2. Lister (who was later made a Lord because of his findings) applied carbolic acid (phenol) to aseptic technique in the operating room 3. Domagk- Sulfa drugs- 1939 4. Fleming, Chain and Florey- Penicillin-1945

19. Immunology-Milestones • Elie Mechnikoff- Cellular Immunology- identified white blood cells as phagocytic immune agents of the blood. • Edward Jenner- showed that an 8 year old could be protected against small pox by introduction of cowpox virus obtained from the lesions of milk maids that had contracted cowpox. Termed the word vaccination (vacca-latin name for cow). • Pasteur use a dried spinal cord of rabbits infected with rabies to develop an anti-rabies vaccine. Drying of the spinal cord effectively attenuates (weakens) the virus. • Gerald M Edleman and Rodney Porter-for their discoveries concerning the chemical structure of antibodies- 1972 • Cesar Milstein, Georges Kohler and Niels Jerne-for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies- 1984 • Tonegawa- for his discovery of the genetic principle for generation of antibody diversity-Received the Nobel prize in 1987. • Doherty and Zinkernagel- Recognition of virus-infected cells by immune defenses. Drs. Doherty and Zinkernagel discovered that T cells simultaneously recognize MHC self-protein and a foreign antigen on the surface of virally infected cells. - We will learn about these findings in the immunology part of the course. Received the Nobel prize in 1996.

20. Bacterial genetics molecular biology-Nobel Prizes The Nobel Prize in Physiology or Medicine 1933 Thomas H. Morgan The Nobel Prize in Physiology or Medicine 1933 Thomas H. Morgan "for his discoveries concerning the role played by the chromosome in heredity“- First Nobel Prize in what would become Molecular Biology/Molecular Genetics Morgan was born in Lexington, Kentucky, to Charlton Hunt Morgan and Ellen Key Howard Morgan.[2][4] Part of a line of Southern planter elite on his father's side, Morgan was a nephew of Confederate General John Hunt Morgan and his great-grandfather John Wesley Hunt had been the first millionaire west of the Allegheny Mountains. Through his mother, he was the great-grandson of Francis Scott Key, the author of the "Star Spangled Banner", and John Eager Howard, governor and senator from Maryland.[