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I always tell my students at the start of every lecture: “If a smart man can understand the entire concept in an hour, while it will take you the whole day to do so, then better start making that coffee.” MICROBES & HUMANS A n ASMPH FILM Introducing WITH THE BUGS OUR WITS versus THEIR GENES “The global future of mankind will probably unfold as episodes of a suspense thriller that could be entitled Our Wits Versus Their Genes.” Joshua Ledeerberg Raul V. Destura MD Consultant-Director Section of Molecular Diagnostics and Section of Clinical Microbiology The Medical City Is a branch of science that relates to interactions between man and microorganisms. In practice, the science deals mainly with the ill health resulting from such interactions – infections or infectious diseases The term is usually applied to any condition that: is easily transmitted between individuals is caused by an identifiable microorganism may, following initial infection, confer protection (immunity) from subsequent infection with the same microorganism. The Affected Host 2. An Infectious Agent 3. The Environment 1. Infectious diseases in man are caused by microorganisms (living organisms of microscopic size) from the following five groups: bacteria viruses Fungi protozoa helminths. Contain the largest number of species that are pathogenic to human Single-celled and contain both DNA and RNA and produces by binary fission A few lack all the machinery necessary for replication and must interact with host cells to reproduce (Ricketsiaceae, Anaplasmataceae, Chlamydiaceae) Single and multicelled agents that are further differentiated into a defined nucleus and cytoplasm Yeast- single celled fungi that reproduce by binary fission Molds or Moulds – more complex multicelled organisms that reproduce by both sexual and asexual means Some are Dimorphic Large and very complex group of microbes Include single celled animals –protozoa Others are very complex, multi-celled organisms that have well defined organs and tissues, such as GI and genital systems Do not have complete genetic machinery for their own propagation Either a DNA or RNA Must infect other life form to survive Represent the simplest form of infectious Agents Reproduce by replication of their nucleic acid Bacteria have been classified on the basis of their staining properties for about 120 years. The method differentiates between two major groups of bacteria with very different cell envelopes. Gram-positive bacteria retain the stain (crystal violet) and appear blue, whereas gram-negative bacteria usually appear pink due to the counterstain safranin. Fig. 7-37b, p.232 Commercial break…….. Developed by: Hans Christian Gram, 1884 Differential stain Discriminates between different cell types – Gram positive and Gram negative Gram positive Dark purple Gram negative Pink Cocci in clusters: e.g. Staphylococci Cocci in chains: e.g., Streptococci Cocci in tetrads: e.g., Micrococci Bacilli or Rods Cocci in pairs (or Diplococci) Bacilli or Rods Issues • selective pressure • antimicrobial resistance • plasmid mediated • chromosomally mediated • Plasmids • Extra-chromosomal DNA • multiple copy number • coding pathogenesis and antibiotic resistance factors • bacterial replication • • • • Some bacteria are motile Locomotory organelles- flagella Taste environment Respond to food/poison – chemotaxis • Flagella – embedded in cell membrane – project as strand – Flagellin (protein) subunits – move cell by propeller like action spirochetes similar function to flagella run lengthwise along cell snake-like movement Making Wall-less forms • Result from action of: – enzymes lytic for cell wall – antibiotics inhibiting peptidoglycan biosynthesis • Usually non-viable • Wall-less bacteria that don’t replicate: – spheroplasts (with outer membrane) – protoplasts (no outer membrane). • Wall-less bacteria that replicate – L forms Mycloplasma Capsules and slime layers • • • • • • outside cell envelope well defined: capsule not defined: slime layer or glycocalyx usually polysaccharide often lost on in vitro culture protective in vivo • • • • • Dormant cell Produced when starved Resistant to adverse conditions - high temperatures - organic solvents contain calcium dipicolinate Bacillus and Clostridium Portals of Entry Respiratory Gastrointestinal Genitourinary tracts Accidental Areas: mucus membranes and skin (A) Portals of entry. (B) Portals of exit. Source of Agent Mechanism for Entry Portal of Entry Example Infected Human Aerosol Respiratory Influenza Virus Infected Human Direct Contact Cutaneous Herpes Simplex in wrestlers Infected Human Sexual Intercourse Genital Syphilis; gonorrhea Infected Human Oral or nasopharyngeal secretions to eye Ocular Bacterial or viral conjunctivitis Contaminated Environment Transfusion of Blood products Intravascular Hepatitis virus Contaminated Environment Food or water Gastroentestinal Enteric bacterial and viral pathogens Infected Animal Cooling tower drift Respiratory Legionaires Disease Infected Tick Animal bite Cutaneous Rabies Patient Tick bite Cutaneous Lyme Disease Patient Aspiration of endogenous flora Respiratory Bacterial Pneumonia Patient Spillage of intestinal flora through a damaged wall Gastroentestinal Bacterial Peritonitis Patient Migration of Bacteria from oropharynx to middle ear through Eustachian tube Ear Bacterial otitis media LD50 and ID50 Some characteristics that give infectious agents a leg up in the battle with their chosen hosts Involves invasiveness and toxigenicity Not an all or none phenomenon Adherence Initial requirement for organisms to invade hosts The process by which bacteria stick to the surface of host cells A.k.a. Adhesion and Attachment Adherence is dictated by several factors Surface hydrophobicity and net surface charge Binding molecules on bacteria (ligands) Host cel receptor interaction Surface hydrophobicity The more hydrophobic the bacterial cell surface, the greater the adherence to the host cell Different strains of bacteria differ in hydrophobicity thus some are more virulent than others Pili (fimbriae) • hair-like projections of the cell • sexual conjugation • adhesion to host epithelium Tissue-Degrading Enzymes Collagenase (C. perfringens) Coagulase (S. aureus) Hyaluronidase (Staph and Strep) Streptokinase (Strep) Hemolysins and Leucocidine IgA1 Proteases Allows pathogens to inactivate the primary antibody found on mucosal surfaces and thereby eliminate protection of the host by the antibody Exotoxins and Endotoxins Properties Mechanisms Exotoxins Endotoxins Excreted by living cells Integral part of cell walls of G- bacteria Produced by both G+ and G- bacteria Found only in G- bacteria Polypeptide; MW 10,000-900,000 LPS complexes (Lipid A) Heat labile Heat Stable Highly antigenic Weakly Immunogenic Can be converted to toxoids Cannot be used as toxoids Highly toxic even at small doses Moderately toxic Has specific binding receptors No specific receptors Usually do not produce fever Induces release of IL-1 and other mediators Plasmid mediated control Chromosomally mediated Exotoxins Endotoxins Diptheria Physiologic Effects Tetanus Fever Botulism Leucopenia Gas Gangrene Hypotension Streptococcal Erythrogenic Toxins Impaired Organ Dysfunction TSST-1 C3 and complement cascade activation Exotoxins associated with diarrheal disease and food poisoning DIC That’s why we need to make sure we clearly understand what we read!