People. Laboratory of Microbial Pathogens and Antimicrobial Therapy ( 病原微生物与抗感染治疗课题组 ) Bacterial infection and antibiotics.

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1 Bacterial infection and antibiotics Laboratory of Microbial Pathogens and Antimicrobial Therapy ( 病原微生物与抗感染治疗课题组 ) Established in December 2012 Xilin Zhao, Ph.D., Professor Dai Wang, Ph.D., Associate Professor School of Public Health, Xiamen University Bacterial infection Antimicrobial resistance New antimicrobial enhancers Bacterial stress response Pathogenesis New antimicrobials Bacterial apoptosis Virulence factors People Group leader Prof. Xilin Zhao,Ph.D Group member Dr. Dai Wang, Assoc. Prof. Dr. Yiqun Liao, Assist. Prof. Ms. Yunxin Xue, Assist. Eng. Postgraduate Student Ms. Jinzhi Feng Ms. Lina Ma Contact us: Tel:+86(0) zhaox5@xmu.edu.cn; daiwang@xmu.edu.cn Xilin Zhao B.S./M.S. (Nankai Univ.) Ph.D. (Univ. East Anglia/ John Innes Centre, UK) Bacterial stress response and programmed cell death Mechanisms of antimicrobial killing Antimicrobial resistance Tuberculosis

2 Dai Wang B.S. (Shanghai Univ.) M.S./Ph.D. (Univ. Edinburgh, UK) Bacterial pathogenesis Type III secretion system Bacterial microrna Yiqun Liao B.S./M.S./Ph.D. (Xiamen Univ.) Molecular diagnosis HBV Drug resistance Bacterial infection is a leading cause of infectious diseases In the past 70 years, 335 human infectious diseases have been discovered, more than half are caused by bacterial infection. Tuberculosis: 10 million new cases per year, ~2 million death Bacterial pneumonia: 4.5 million cases a year, 60,000 death (US) Cholera: 5.5 million cases a year, 130,000 death. Black death (Plaque) caused by Yersinia pestis infection killed 75 to 200 million, about half of European population. Spontaneous generation v.s. Spontaneous generation was coherently synthesized by Aristotle different types of life might repeatedly emerge from specific sources other than seeds, eggs or parents. life routinely emerges from non-living matter on a time scale of anything from minutes to weeks (mice and other animals arise from the mud of the Nile; aquatic forms being produced directly from lifeless matter) The germ theory of disease refers to the discovery in the late 19th century that some infectious diseases are caused by microorganisms, small organisms too small to see without magnification, that invade the host.

3 Significant contributors of Bacteria were first discovered by Antonie Philips van Leeuwenhoek in the 1670s Significant contributors of Discovered germ theory of fermentation Invented pasteurization for sterilization He is considered as the Father of Microbiology since he used handcrafted microscopes to first observed many different single celled organisms. Created the first vaccine Louis Pasteur Significant contributors of Founder of modern bacteriology Identified the specific causative agents of tuberculosis, cholera, and anthrax Koch's Four Postulates 1. The organism must always be present, in every case of the disease. 2. The organism must be isolated from a host containing the disease and grown in pure culture. Created the Koch s postulates for linking specific microorganisms to particular diseases Invented multiple methods for culturing pure bacteria (Potato slice, gelatin, agar) Robert Koch 3. Samples of the organism taken from pure culture must cause the same disease when inoculated into a healthy, susceptible animal in the laboratory. 4. The organism must be isolated from the inoculated animal and must be identified as the same original organism first isolated from the originally diseased host.

4 Significant contributors of Pioneered antiseptic surgery Bad air or bacterial transmission Filtration, exposure to heat, exposure to chemicals Transmittable infectious diseases used to be the leading cause of human death The 1918 Spanish Flu: Infected 500 million people and killed million Unlike most other influenza outbreaks that disproportionately kill juvenile, elderly, or already weakened patients; the 1918 pandemic killed predominantly previously healthy young adults. Carbolic acid (now known as phenol) Joseph Lister The majority of deaths were from bacterial pneumonia, but the virus also killed people directly, causing massive hemorrhages and edema in the lung. Ended the World War I due to lack of troops supply Tuberculosis Characteristics of M. tuberculosis Bacterial infection caused by Mycobacterium tuberculosis Damages lungs or other parts of the body Fatal if not treated properly Slow growing High bacterial burden Waxy cell wall Refractory to chemotherapy

5 The challenge for tuberculosis control cholera A third of human population are infected, ~10 million new cases (~2 million deaths) per year. Slow growing pathogen, high bacterial burden, dormancy. Long treatment time with multiple agents required. Increasing prevalence of MDR, XDR, and CDR cases. Caused by vibrio cholerae infection (O1, and O139) Transmits through contaminated food and water 3-5 million cases, 130,000 death in 2010 Used to be a much deadly disease, killing tens of millions in 19 th century 7 cholera pandemics have occurred in the past 200 years, with the seventh originating in Indonesia in Plague (Black death) Occurred during Caused by Yersinia pestis infection started in China or central Asia and travelled along the Silk Road and reached the Europe by 1346 Killed million or near half of European population THE 10 LEADING CAUSES OF DEATH AS A PERCENTAGE OF ALL DEATHS, U.S Pnuemonia Diarrhea and Enteritis Stroke Injuries Senility Tuberculosis Heart disease Liver disease Cancer Diphtheria % of all deaths 2 other major outbreaks of had been occurred: The Plague of Justinian in the 6th and 7th centuries, wiped out half of European population China and India in the 1890s, also killed millions. Heart disease Stroke Injuries Diabetes Suicide Cancer Lung disease Pnuemonia & Influenza HIV Liver disease % of total

6 The Decline of Infectious Diseases 1. Increased hygiene and sanitation (chlorinated drinking water, sewage treatment etc.) 2. Antibiotics 3. Childhood vaccination programs DEFINITIONS Antibiotic: compound produced by a microorganism that kills or inhibits the growth of another microorganism. Antimicrobial: Antibiotics and synthetic compounds that kills or block the growth of microorganisms including bacteria, fungi, viruses, and even protozoans. History of antibiotic discovery Year Origin Description 1640 England John Parkington recommended using mold for treatment in his book on pharmacology 1870 England Sir John Scott Burdon-Sanderson observed that culture fluid covered with mould did not produce bacteria 1871 England Joseph Lister experimented with the antibacterial action on human tissue on what he called Penicillium glaucium 1875 England John Tyndall explained antibacterial action of the Penicillium fungus to the Royal Society 1877 France Louis Pasteur postulated that bacteria could kill other bacteria (anthrax bacilli) 1897 France Ernest Duchesne healed infected guinea pigs from typhoid using mould (Penicillium glaucium) 1928 England Sir Alexander Fleming discovered enzyme lysozyme and the antibiotic substance penicillin from the fungus Penicillium notatum 1932 Germany Gerhard Domagk discovered Sulfonamidochrysoidine (Prontosil ) 1943 USA Selman Waksman discovered streptomycin History of antimicrobial discovery Paul Ehrlich: father of chemotherapy, initiated the concept of chemotherapy (1904), discovered Salvarsan (1910) for the protozoal disease sleeping sickness. Prontosil (Gerhard Domagk, 1932, 1935) against streptococcal infections, later recognized as a prodrug for the first class of true antibacterial Sulfonamides Penicillin: first true antibiotic, discovered 1928 by Alexander Fleming but not widely used clinically until Streptomycin: Selman Waksman Additional reading materials:

7 The initiation of the concept of chemotherapy The father of chemotherapy Initiated the concept of chemotherapy (1904) Discovered Salvarsan (1910) for the protozoal disease sleeping sickness and syphilis. Won Nobel price for his work on acquired Immunity in 1908 Pioneered antiseral valency standards. Coined the concept of magic bullet. Paul Ehrlich The Discovery of Sulfonamides In 1932, Gerhard Domagk discovered that a red dye, called prontosil rubrum, protected mice and rabbits against lethal doses of staphylococci and haemolytic streptococci. Prontosil was a derivative of sulphanilamide (p-aminobenzenesulphonamide), which the Viennese chemist, Gelmo, had synthesized in In 1935, Prontosil was shown clinically effective against streptococcal infection, landing Domagk Nobel Price in Gerhard Domagk Discovered the existence of blood-brain barrier. Penicillin Discovery of penicillin Staphyloccus aureus Fungus: Penicillium notatum Ernest Duchesne The Discovery of streptomycin Father of antibiotic, a word he coiled. Discovered streptomycin, neomycin, and >15 other antibiotics Noble price in 1952 for his discovery of streptomycin, the first antibiotic effective against tuberculosis Sir Alexander Fleming Ernst Chain Sir Howard Florey Andrew J. Moyer The Nobel Prize in Physiology or Medicine 1945 "for the discovery of penicillin and its curative effect in various infectious diseases". Controversy about proper credit for streptomycin discovery with his student, Albert Schatz. Selman Waksman

8 The mission of scientist A quiz Uncover the law and truth of mother nature Persist (truth often lies in the hands of minority) Challenge authority (Respect law of nature more than respect any person Comprehensive (no rush to conclusion, self-correct) Unlimited imagination 1. Which month has 28 days? 2. What can t you ever grab with your right hand? 3. How many eggs can you eat with an empty stomach? 4. Can you imagine something that might travel faster than light? Suggested reading: The structure of Scientific Revolutions by Thomas S. Kuhn