HOSTMICROBE RELATIONSHIPS AND DISEASE PROCESSES CHAPTER 14 Copyright

Host-microbe relationships Symbiosis- is an association between two (or more) species. 1) mutualism- both members of the relationship benefit 2) commensalis- two species live together in a relationship such that one benefits and the other one neither benefits nor is harmed. 3) parasitism- one organism, the parasite, benefits from the relationship whereas the other organism, the host is harmed. The lines between these different symbiotic relationships is not always clear- by taking up residence on the skin and utilizing nutrients microbes that show mutualistic or commensalistic behavior may prevent colonization of the skin by other, potentially harmful, disease-causing microbes a phenomenon known as microbial competition. Also between parasitism and commensalism- normally harmless organisms can become parasitic if it gains entrance to certain parts of the body.

Contamination, infection and disease. Contamination-microorganisms are present. Infection- multiplication of any parasitic organism within or upon the host’s body-does not necessarily result in disease Disease- disturbance in the state of health wherein the body cannot carry out all its normal functions

Pathogens, pathogenicity and virulence Pathogenicity is the capacity to produce disease. Pathogenicity depends on the ability of an organism to invade and avoid the hosts defense mechanisms, and to multiply. Virulence-refers to the intensity of the disease produced by pathogens and it varies among different microbial species. The virulence of a pathogen can be decreased by attenuation, the weakening of the disease producing ability of the pathogen. Attenuation can be achieved by repeated subculturing on laboratory media or by transposal of virulence (e. g, . Passage of rabies virus through a rabbit until it was no longer virulent in humans).

The yellow area give examples (not complete by any means) of how these systems may be Compromised or how they set an environment for infection. removal of ciliated cells by influenza vir antibiotics burns, cuts aeration, macrophage delivery diseases of the blood or systemic bacterial infections acid loving bacteria- Helicobacter pylori Rhinovirus cannot survive the rapid p. H change antibiotics not sufficient fluids Natural body defenses against infection

Among the resident and transient microflora are some species of organisms that do not usually cause disease but can do so under certain conditions. These organisms are termed opportunists and conditions that create opportunities for these organisms include: 1. Failure of the host’s normal defenses, e. g, immunocompromised (AIDS, Transplant, chemotherapy), severe burns. 2. Introduction of the organisms in unusual body sites e. g, E. coli in urinary tract, or S. aureus in the brain. 3. Disturbances in the normal microflora- e. g, caused by some antibiotics.

Koch’s Postulates: 1. The specific causative agent must be observed in every case of a disease 2. The agent must be isolated from a diseased host and must be grown in pure culture. 3. When the agent from the pure culture is inoculated into healthy, but susceptible, experimental hosts, the agent must cause the same disease 4. The agent must be re-isolated from the inoculated disease experimental host an identified as identical t the original specific causative agent. Not all infectious diseases can fulfill Koch’s postulates (bacterial or viral diseases in which the organisms cannot be cultured, e. g. , syphilis, viral diseases), however, the approach to establishing whether or not an organism is responsible for a disease uses Koch’s postulates as a guideline.

Kinds of Diseases Infectious and noninfectious diseases. Infectious diseases are diseases cause by infectious agents such as bacteria, viruses, fungi, protozoa and helminths (we will not cover the latter two categories in this course). Noninfectious diseases are caused by any other agents than infectious organisms. Contagious disease-A contagious disease is a subset category of infectious diseases (or communicable diseases), which are easily transmitted by physical contact (hence the name-origin) with the person suffering the disease, or by their secretions or objects touched by them. [ When diseases are discovered to move from the bottom category (noninfectious disease) to the top category (infectious disease) a cure or partial cure is often accomplished (e. g. , ulcers or cervical carcinoma).

Communicable and noncommunicable diseases Communicable- can be spread from one host to another Contagious diseases- communicable diseases that are more easily spread than others-such as, influenza, common cold, rubella Noncommunicable infectious disease- are not readily spread from one host to another, e. g. , tetanus, botulinum, legionellosis,

The Disease Process- How Microbes Cause Disease

How bacteria cause disease. Virulence factors- structural or physiological characteristics that help organisms cause infection and disease, e. g. , pili for adhesion to cells (famous gonorrhea study), capsules to prevent phagocytosis, enzymes, such as hyaluronidase that help to digest tissues. Direct actions of bacteria- Bacteria can enter the body by penetrating the skin or mucous membranes, by sexual transmission, ` by being ingested with food, by being inhaled in aerosols, or by transmission on a fomite (inanimate object). If the bacteria are immediately swept out of the body they cannot initiate infection. Adherence or attachment, is a critical point in the production of bacterial disease Adhesin are proteins or glycoproteins found on attachment pili (fimbrae) and capsules. Also organisms such as Shigella appear to attach via their LPS.

Adhesin are proteins or glycoproteins found on attachment pili (fimbrae) and capsules.

Colonization- is another critical point in the production of disease and it refers to the growth of microorganisms on epithelial surfaces, such skin or mucous membranes or other host tissues. Again a question of adherence (adhesins).

Invasiveness- only a few pathogens cause disease by colonizing surfaces; most have additional virulence factors that enable the pathogen to invade tissue, i. e. . invasiveness

pathogens coagulase hyaluronidase blood clot streptokinase Fig. 14. 5 Enzymatic virulence factors help bacteria invade tissues and evade host defenses

Bacterial Toxins Endotoxins Exotoxins • Gram negative • Gram positive • LPS • Proteins, usually enzymes • Fever • Potent effects • Shock • Specialized tissue damage • Released at cell death • Secreted Copyright © 2012 John Wiley & Sons, Inc. All rights reserved.

Bacterial toxins- A toxin is any substance that is poisonous to other organisms. Exotoxins- soluble substances secreted into host tissues-are mostly polypeptides more powerful and specific than endotoxins, and can be denatured by heat to form toxoids. The Gram positive species of Clostridium, Bacillus, Staphylococcus, Streptococcus and several other bacteria produce exotoxins. Vibrio cholerae and toxigenic E. coli are Gram negative organisms that produces a potent exotoxins. Many exotoxins are of the A-B type (slide 20). The B subunits bind to the surface membrane of the cell, whereas, the A subunit is the business end. Endotoxins- are part of the cell wall (LPS), of gram negative organisms, that are released into host tissues when the bacteria die or divide. Endotoxins have nonspecific effects such as fever or a sudden drop in blood pressure. They also cause tissue damage in diseases such as typhoid fever and epidemic meningitis.

Adhesins are proteins or glycoproteins found on pili and capsules A. True B. False

New, aggressive form of HIV identified in Cuba In Cuba, a variant of HIV that is much more aggressive than other known forms of the virus has been documented. Patients infected with this new variant progress to AIDS so rapidly that they may not even know they are infected, with AIDS symptoms occurring within 3 years of infection. If a person contracts multiple strains of HIV - typically by engaging in unprotected sex with multiple infected partners - then these strains can recombine into a new variant of HIV within the host. The new Cuban variant of HIV is one such recombinant version of the virus. HIV anchors itself to co-receptors - proteins on the membranes of cells before the virus is able to penetrate the cell. The first co-receptor that HIV anchors to is known as CCR 5. Then, after a number of years of normal health, the virus switches to the anchor point CXCR 4, which results in a faster progression to AIDS. In the recombinant form of HIV identified in Cuba, HIV makes the transition to CXCR 4 shortly after infection, reducing the healthy phase and initiating the progression to AIDS. The patients with the recombinant HIV were found to have abnormally high doses of the virus and defensive molecules called RANTES is part of the human immune response and binds to CCR 5 - the co-receptor that HIV initially anchors onto after infection.

Hope for people with Parkinson’s Scientists at Harvard University say they see promising signs from their study on an experimental treatment for Parkinson's disease. The researchers transplanted tissue from fetal dopamine cells into the brains of patients with Parkinson’s in Canada. Patients with severe symptoms experienced 50% fewer symptoms in the years after surgery. People who had been taking medication to control their Parkinson’s but found that the medicine no longer worked also saw significant improvements after surgery. Looking at the brains of five patients after they died from non-Parkinson’s related illnesses, the scientists found that the transplanted cells stayed healthy. Earlier research led scientists to hypothesize that the cells would become corrupted, but the cells remained functional for at least 14 years after the patients got them. This is the first proof that this kind of transplant method could work. "Though it is encouraging and even exciting to see some PD cells survive over a decade following a human transplant, we are still humbled by the challenges in developing a viable therapy, " Dr. Michael Okun, national medical director for the National Parkinson Foundation, cautioned. "All transplants for Parkinson's disease remain hampered by an inability to constitute a complex multilevel brain circuitry. "

Action of endotoxin a, or active subunit Action of exotoxin Action of exo- and endotoxinimportant and not in your text b, or binding subunit A-subunit alters cell function

DT= diphtheria toxin Nicotinamide-adenine-dinucleotide-phosphateribose (NADP) ADP-ribosylation is a mechanism used by many toxins. The target proteins differ (diphtheria ADPribosylates the EF factor; cholerae toxin ADP-ribosylates adenylcyclase). Figure of ADP ribosylation- the most common mechanism of Bacterial toxin action- Typical of diphtheria toxin

Clostridium botulinum Blocks muscle contraction Clostridium tetanus –blocks muscle contraction inhibition Botulinum toxin blocks the release of neurotransmittor

ADP-ribosylates the protein that regulates the synthesis of of cyclic AMP. The result is highly elevated levels of cyclic AMP which in turn results in a blockage in movement of Na+ into the tissues and an outflow of Cl- ions into the lumen. The gut has a marked increase in Na. Cl. Action of choleratoxin

How viruses cause disease In cultured cells viruses cause observable changes termed cytopathic effect (CPE) Viral infections can be productive or abortive. Productive infection occurs when viruses infect a cell and produce infectious offspring Abortive infection occurs when viruses enter a cell but are unable to make offspring (viruses used for gene therapy are typically engineered to have an abortive infection). Latent viral infections- a virus that remains inactive typically for a relatively long period but has the potential to be reactivated, e. g. , varicella/zoster, or HSV, Persistent viral infection- hepatitis B virus

B e Before viral infection After viral infection Fig. 14. 7 An example of the cytopathic effect (CPE)

Fig. 14. 9 Stages in the course of an infectious disease

Infectious Diseases- Past, Present and Future

1918 -flu pandemic Fig. 14. 11 Changes in the Causes of death in the US From 1900 to the 1990’s