Microbe-Human Interactions 2024 UiTM PDF

Microbe-Human Interactions This lecture explores the fascinating world of microbes and their interactions with humans. We will discuss the diverse world of microbes, their roles in maintaining health and causing disease, and the microbiome's influence on various aspects of human well-being. by Ka...

Microbe-Human Interactions This lecture explores the fascinating world of microbes and their interactions with humans. We will discuss the diverse world of microbes, their roles in maintaining health and causing disease, and the microbiome's influence on various aspects of human well-being. by Kalavathy Ramasamy, Faculty of Pharmacy, UiTM preencoded.png Infectious Disease Resurgence in Malaysia Infectious diseases, once thought to be under control, are making a comeback in Malaysia. This presentation explores the trends, causes, and challenges associated with this resurgence. KR preencoded.png Dengue Fever: A Persistent Threat 1 Mosquito Bite An infected Aedes mosquito bites a human, transmitting the dengue virus. 2 Virus Replication The virus multiplies within the body, leading to symptoms like fever, headache, and muscle pain. 3 Transmission The infected person can then transmit the virus to other mosquitoes through bites, continuing the cycle. preencoded.png Common infection Diseases in Malaysia Chikungunya: The Comeback Virus 1 Mosquito Bite An infected Aedes mosquito bites a human, transmitting the virus. 2 Virus Replication The virus multiplies within the body, causing symptoms like fever and joint pain. 3 Transmission The infected person can then transmit the virus to other mosquitoes through bites. preencoded.png Malaria: Combating a Global Scourge Mosquito Bite An infected female Anopheles mosquito bites a human, transmitting the malaria parasite. Parasite Development The parasite multiplies and develops within the mosquito, eventually reaching the salivary glands. Transmission When the infected mosquito bites another human, the parasites are injected into the bloodstream. preencoded.png Tuberculosis: Tackling a Resurgent Disease Infection Transmission Symptoms Tuberculosis (TB) is a bacterial TB spreads through the air when an Symptoms include persistent cough, infection that primarily affects the infected person coughs, sneezes, or chest pain, fever, and weight loss. lungs. speaks. preencoded.png Tuberculosis  Objectives 1. Normal Microbiota (Relationship between normal microbiota and the host; Opportunistic microorganisms and pathogens). 2. Microbes and Human Interactions (Occurrence of disease, Severity of diseases, Patterns of infections) 3. The Spread of Infection (Reservoirs of infection, Patterns of transmission and transmission of disease) 4. Microbial Mechanisms of Pathogenicity (Major factors in development of an infection, Portals of entry, How bacterial pathogens penetrate host defences, Mechanisms of exotoxin and endotoxin)  Objectives 1. Normal Microbiota (Relationship between normal microbiota and the host; opportunistic microorganisms) Human Microbiome Project, NIH  Print of invisible bugs from one’s hand https://www.youtube.com/watch?v=j1GLbqW3zAI Commensal Microbes: Coexisting with Humans Skin Microbes Gut Microbes These microbes help protect They aid digestion, synthesize against pathogens and maintain vitamins, and regulate immune skin health. function. Respiratory Microbes They help prevent colonization by harmful pathogens, contribute to immune system development. preencoded.png Pathogenic Microbes: Causing Disease Infection Pathogens invade host tissues and multiply, causing harm. Virulence Factors Pathogens possess toxins, enzymes, or other mechanisms to damage host cells. Immune Evasion Some pathogens evade the host's immune system, prolonging infection. preencoded.png The Human Microbiome 1 Gut Microbiome The gut microbiome plays a key role in digestion, nutrient absorption, and immune system development. It also influences metabolism and overall health. 2 Skin Microbiome The skin microbiome acts as a barrier against pathogens, maintains skin integrity, and helps regulate immune responses. 3 Respiratory Microbiome The respiratory microbiome plays a role in immune system development, protection against respiratory infections, and maintaining lung health. 4 Vaginal Microbiome The vaginal microbiome maintains a healthy vaginal environment, prevents infections, and supports reproductive health. preencoded.png  Maintenance of the Normal Resident Flora Staphylococcus sp on epithelial cells Normal flora/ Normal microbiota/commensal/residents/indigenous is essential for human health. Normal microflora creates an environment sciencephotolibrary.tumblr.com that may prevent infections and can improve host defenses. Lactobacilli 500 different bacterial genera but only 10% of these species may be pathogens. Pathogen – infectious agent https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Relationship between Normal Microbiota and the Host Staphylococcus sp on epithelial cells Normal microbiota can benefit the host by preventing overgrowth of pathogens via competitive exclusion or microbial Commensal antagonism. The normal microbiota protect the host against colonization by competing for nutrients, producing substances that are harmful for pathogens, affect Lactobacilli conditions such as pH and available oxygen. Eg. vaginitis: infection in the vagina Normal microbiota maintains pH of about 4 in the human vagina and usually inhibits yeast, Candida albicans. However when there an imbalance, and pH is altered to pH 7 with the use of antibiotics for example will result in overgrowth of C. albicans resulting in vaginitis. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Eg. Clostridium difficile infection in the large intestine Pathogens  Maintenance of the Normal Resident Flora Most areas of the body in contact with the outside environment harbor resident microbes. Residents – microbes that become established. Internal organs, tissues, and fluids are microbe-free Transients – microbes that occupy the body for only short periods. Host with compromised immune system could be easily infected by these residents. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Table 13-2 20 Normal/resident flora in specific region 21 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Flora of the Human Skin Copyright © McGraw-Hill Education. Permission required for reproduction or display. Hair shaft Skin is the largest and Epidermis most accessible organ Sweat pores Two cutaneous Sebaceous (oil) gland populations Dermis Hair follicle – Transients: influenced Hair root by hygiene Subcutaneous Duct of – Residents: stable, tissue sudoriferous (sweat) gland predictable, less (a) influenced by hygiene (b) 22 Janice Carr/CDC Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Flora of the Mouth Most diverse and unique flora of the body. Numerous adaptive niches. Bacterial count of saliva (5 x 109 cells per milliliter) Most common is streptococci 23 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Flora of the GIT Copyright © McGraw-Hill Education. Permission required for reproduction or display. Oral cavity Pharynx Has the most amount of microbes (108-1011 microbes per gram of feces) Esophagus Intestinal environment favors Stomach anaerobic bacteria and aerotolerant bacteria. Duodenum Intestinal bacteria contribute to Large intestine intestinal odor Small intestine Variations in flora distribution due to shifting conditions (pH, Rectum oxygen tension, anatomy) 24 Anal canalEducation. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill  Initial Colonization of the Newborn Copyright © McGraw-Hill Education. Permission required for reproduction or display. Uterus and contents are normally sterile and remain so until just before birth Breaking of fetal membrane exposes the infant; all subsequent handling and feeding continue to introduce what will be normal flora Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 25  Relationship between Normal Microbiota and the Host Staphylococcus sp on epithelial cells Normal microbiota can benefit the host by preventing overgrowth of pathogens via competitive exclusion or microbial Commensal antagonism. The normal microbiota protect the host against colonization by competing for nutrients, producing substances that are harmful for pathogens, affect Lactobacilli conditions such as pH and available oxygen. Eg. vaginitis: infection in the vagina Normal microbiota maintains pH of about 4 in the human vagina and usually inhibits yeast, Candida albicans. However when there an imbalance, and pH is altered to pH 7 with the use of antibiotics for example will result in overgrowth of C. albicans resulting in vaginitis. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Eg. Clostridium difficile infection in the large intestine Pathogens  Relationship between Normal Microbiota and the Host: Terms Staphylococcus sp on epithelial cells There is a symbiosis relationship between the normal microbiota and the host. Commensalism and mutualism are types of symbiosis relationship. Commensalism: One of the organism is dependent on the other Eg: Staphlocococcus epidermidis that inhabit the surface of the skin. It Lactobacilli lives on secretions and dead cells and bring no harm to the host. Mutualism: type of symbiosis that benefits both organism. Eg. Lactobacilli can produce vitamins for use of body cells whilst the bacteria depends on the nutrients in the large intestine to survive. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Opportunistic microorganisms Staphylococcus sp on epithelial cells A microorganism like E.coli is generally harmless in the large intestine but if it gains access to other parts of the body sites, it can cause diseases. Urinary bladder : causes UTI Lung: pulmonary infection Lactobacilli Wounds: abscesses Opportunistic pathogens causes disease: 1. at different body sites and not at their normal habitat 2. in immunocompromised subjects. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Quick Recap of the First Objective 1. What are normal flora known: Resident , commensal 2. What are transient microbes? 3. What are sterile All internal organs and Fluids within an organ or tissue 4. Common resident flora in large intestine are? Lactobacilli, Bifidobacteria and E. coli 5. Is E. coli a resident flora of the urinary tract? It is an opportunistic in urinary tract 6. Relationship between resident flora and the host https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Objectives 2. Microbes and Human Interactions (Occurrence of disease, Severity of Disease, Patterns of infections) Human Microbiome Project, NIH  Occurrence of a Disease Infection – a condition in which pathogenic microbes penetrate host defences, enter tissues, and multiply. Infectious disease – an infection that causes damage or disruption to tissues and organs (abnormal state in which part or all of the body is incapable of performing its normal function). Incidence: the number of people in a population who develop a disease (new cases) during a particular time period. Prevalence: the number of people in a population who develop a disease at a specified time, regardless of when it first appeared. Eg: a person who is newly diagnosed with diabetes is an incident case, whereas a person who has had diabetes for 10 years is a prevalent case. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  32 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Frequency of occurrence to classify disease Sporadic disease – disease occurs only occasionally (Eg typhoid fever) Endemic disease– a disease constantly occurring in a particular population (common cold) Epidemic disease: If many people in a given area acquire a certain disease in a relatively short period (Initially COVID19 was thought to be epidemic at China but eventually it became a pandemic) Pandemic: An epidemic disease that occurs worldwide. https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Occurrence of a Disease Lactobacilli https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  R0 R0, the basic reproduction number = is defined as the expected number of secondary cases produced by a single (typical) infected person in a completely susceptible population. It specifically applies to a population of people who were previously free of infection and haven’t been vaccinated. Lactobacilli Measles has one of the highest numbers with an R number of 15 in populations without immunity. That means, on average, one person will spread measles to 15 others. Can we measure the R0 for COVID19 now? https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  R0 If the R-value is above one then the number of cumulative cases takes off, but if it is below one then eventually the outbreak stops. The further below one, the faster that happens. Lactobacilli https://www.dailymail.co.uk/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Malaysia has successfully reduced the R0 value from 1.5 37 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Patterns of Infection (host involvement) Mixed infection – several microbes grow simultaneously at the infection site - polymicrobial Primary infection – initial infection Secondary infection – caused by an opportunistic pathogen after the primary infection Primary (urinary) infection (e) Secondary (vaginal) Various infection microbes 38 (d) Mixed infection  Patterns of infection Acute infection – comes on rapidly, with severe but short-lived effects Chronic infections – progress and persist over a long period of time Vaccination can provide protection to an infectious disease, thereby reducing the occurrence. When many immune people are present in a community, it is known as herd immunity. 39  Patterns of Infection Localized Localized infection – microbes enter the body and infection (boil) remains confined to a specific tissue. Eg boils or abscess. Systemic infection – infection spreads to several Systemic infection sites and tissue fluids usually in the bloodstream. (influenza) Eg measles Focal infection – when infectious agent breaks Focal infection loose from a local infection and is carried to other tissues (infections from tonsils or sinuses) 40  Stages of Infection 1) Incubation period (The interval between initial infection and the first signs and symptoms). The agent is multiplying at the portal of entry. Overall incubation period can range from several hours eg pneumonia to several years in leprosy. In general majority of infections: 2-30 days. 2) Prodromal period (The short period after incubation where there are early, mild symptoms, head and muscle ache, stomach upset. Usually 1-2 days. 1) Period of Invasion (When the disease is most severe, it is the height of the infection). Multiply at high levels exhibiting greatest toxicity and becomes established at the target tissue. Often marked by fever, and more specific signs (cough, swelling, jaundice severe pain). The length is extremely variable. 2) Period of convalescence (When the body returns to its pre-diseased state or death). The patient’s strength and health gradually return as the immune response begins to clear the infectious agent and restore normal function. 41 This is general: must be considered based on the agent.  Objectives 3. The spread of infection (Reservoirs of infection, patterns of transmission and transmission of disease)  Terms (transmission of infectious agents) Communicable disease – when an infected host can transmit the infectious agent to another host and establish infection in that host. Highly communicable disease is contagious Non-communicable infectious disease does not arise through transmission from host to host 43 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Sources and transmission of microbes Reservoir primary habitat of pathogen in the natural world Human or animal carrier, soil, water, plants 44 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  a) Human Reservoirs Carrier – an individual who unnoticeably shelters a pathogen and spreads it to others; may or may not have experienced disease due to the microbe. Asymptomatic carrier – shows no symptoms Passive carrier – contaminated healthcare provider picks up pathogens and transfers them to other patients Passive (c) Transfer of infectious agent through contact Infectious agent 45 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  b) Animals Reservoirs An infection indigenous to animals but transmissible to humans is a zoonosis (Eg, Rabies, Leptospirosis). At least 150 zoonoses exist worldwide; make up 70% of all new emerging diseases worldwide Transmission Direct contact; bite Airborne Waterborne Food-borne 46 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Rabies outbreak in Sarawak 2018 47 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Intermediate host palm civets Natural host 48 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Nipah virus 49 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  50 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Patterns of Transmission (Contact transmission) Direct contact – physical contact or “person to person transmission”, no intermediate host (STD) Respiratory Droplet transmission (close contact) – microbes are spread by mucous droplets that travel only short distances. Less than 1 meter. One sneeze may produce 20,000 droplets (ebola, chicken-pox) Indirect contact – agents of disease transmitted from its reservoir to a susceptible host by non-living object. Fomite: non-living object involved in the spread of infection (Handkerchief, door knobs etc) 51 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Patterns of Transmission (Vehicle transmission) Vehicle transmission: transmission of disease agents by a medium such as water, food, air, blood etc. Waterborne transmission: pathogens are spread by contaminated water or sewage (cholera by Vibrio cholerae). Foodborne transmission: incompletely cooked or unsanitary conditions (Eg. Salmonellosis, Salmonella typhi and Vibrio cholerae) Airborne transmission: spread of infections agents via droplet nuclei (dried microscopic residues), aerosols due to wind (fine dust or particles in air that contains live pathogens) that travel more than 1 meter. Eg. TB and measles (paramyxovirus). (up to 5 m). TB: Once coughed out by a person with TB, the bacilli can survive up to six53 months outside the body if they are protected from direct sunlight. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  54 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. How Communicable Infectious Diseases are Acquired Respiratory droplets Droplet nuclei 55 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Common Zoonotic Infections Rabies is mainly through saliva of animals (dogs) COVID19 56 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Leptospirosis http://www.caribvet.net/en/system/files/users/marion%20laurent/b2200219-leptospira_interrogans_bacterium-spl_1.jpg Source: http://cdn.epicski.com/6/63/63169f9b_curvy-road.jpeg Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Transmission of Disease (Vectors) Mainly by arthropods. Mechanical transmission: passive transport. Biological transmission : active transmission. The arthropods bites an infected person and ingests some of the infected blood and then transmits to another host. 58 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Hospital acquired infections Nosocomial infections are diseases that are acquired or developed during a hospital stay Every effort is made to kill or check the growth of microorganisms but the hospital environment is a major reservoir for pathogens. From surgical procedures, equipment, and personnel, are exposed to drug-resistant microorganisms 59 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Recap: Objectives 2 and 3 Classification of disease (sporadic, endemic, epidemic, pandemic) R0 Reservoir: Human and Animals (zoonotic infections) Patterns of Transmission (Direct, Indirect, Droplet, waterborne, airborne, foodborne, vehicle) Influenza: TB: Salmonellosis: Typhoid: Cholera: Leptospirosis: Transmission of disease (vectors) 60 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Objectives 4. Microbial mechanisms of pathogenicity (major factors in development of an infection, portals of entry, how bacterial pathogens penetrate host defences, mechanisms of exotoxin and endotoxin)  Major factors in the development of an infection Phase 1 Phase 2 Phase 3 Source of infectious agent can be exogenous or endogenous (gut microbiota) Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 62  Portals of entry (Phase 1) Mucous membrane Many pathogens gain access to the body by penetrating mucous membranes lining the respiratory tract, GIT and conjunctiva (delicate membrane that covers the eyeballs). Skin cuts, abrasions, punctures, incisions Gastrointestinal tract food, drink, and other ingested materials Respiratory tract oral and nasal cavities 63 Urogenital tract Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Requirement for an Infectious Dose (ID) Minimum number of microbes required for infection to proceed. Microbes with small IDs have greater virulence. Lack of ID will not result in infection 64 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Portals of entry (Phase 2): Adherence Adhesion – is a necessary step in pathogenicity. The attachment between pathogen and host is by surface molecules (adhesins or ligands) that binds specifically to receptors on the cells of the host. Adhesins are located at glycocalyx or pilli, or fimbriae etc. Fimbrae Glycocalyx Cilia Suckers Hooks Barbs 65 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Adhesion Properties of Microbes 66 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Portals of entry (Phase 3): Surviving host defenses Capsule Bacteria cannot be engulfed Virulence factors: traits used to invade and establish themselves. Blocked Initial response of host defenses comes Phagocyte Continued growth of microbes damages from phagocytes. Anti-phagocytic factors host tissue (c) Blocked phagocytic response – used to avoid phagocytosis Slime layer or capsule – makes phagocytosis difficult. Ability to survive intracellular phagocytosis (S. pneumoniae) S. Pneumoniae Strains without capsule Cell wall component are avirulent Eg. Streptococcus pyogenes M protein is acid and heat resistant Resist phagocytosis. 67 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Portals of entry (Phase 3): Surviving host defenses Enzymes and Toxins Common enzymes Hyaluronidase : digests hyaluronic acid, the substance that cements cells together Keratinase Collagenase. Toxigenicity – capacity to produce toxins at the site of multiplication Epithelial cell Bacteria Exotoxins Cell Bacteria cement Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. (a) Exoenzymes (b) Toxins  Portals of entry (Phase 3): Bacterial toxins 2 Types of Bacterial Toxins: Exotoxin – toxin molecule secreted by a living bacterial cell into the infected tissue Strong specificity for a target cell Hemolysins (disrupts cell membrane of red blood cells). A-B toxins (A-active, B-binding) Toxin produced by C. tetani Toxin produced by C. botulinum (the cosmetic form referred to as "Botox" by patients, is a popular injectable that Endotoxins temporarily reduces or eliminates facial fine lines and wrinkles) Endotoxin – toxin that is not secreted but is released after the cell is damaged Composed of lipopolysaccharide (LPS), part of the outer membrane of Gram- negative cell walls 69 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  70 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Comparing Exotoxins & Endotoxins 1mg of botulinum toxin is enough to kill 1 million guinea pigs Exotoxin can be inactivated by heat and formaldehyde. This will stimulate the body to produce antitoxins CAP TD MESS P=pneumonia 71 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Exotoxins Exotoxins Types of Exotoxins 1. A-B toxins 2. Membrane disrupting toxins (mainy staphylococci and streptococci) Leukocidins: kills phagocytic leukocytes Hemolysin: destroys red blood cells. 3. Superantigens: antigens that provoke a very intense immune system. (a) Target organs are damaged; heart, muscles, blood 72 cells, intestinal tract show dysfunctions. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  A-B Exotoxins Toxin precursor (inactive) A chain A Secreted by a number of B chain B pathogenic bacteria. B chain attaches to receptor A The A (active) component Binding site B is attached to the B Host cell (binding) component membrane with specific Endocytosis receptor The A component is Vacuole A formation released in the cytoplasm B which inhibit synthesis of proteins required for normal function of host. A portion of toxin is released B from vacuole A Toxin acts on ribosomes 73 and blocks protein synthesis; causes cell deat Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Endotoxins It is very important to have a sensitive test to identify presence of endotoxin in drugs, medical devices and body fluids. The endotoxin can cause endotoxic shock (due to excessive secretion of pro-inflammatory cytokines) 74 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Major Factors in the Development of an Infection Phase 1 Phase 2 Phase 3 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. 75  The different stages 76 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Recap: Objective 4 Portal of entry Important is 2 and 3 Phase 2: Adhesion Phase 3: Virulence factors Anti-phagocytosis, capsule/slime layer) Enzymes and Toxins (exotoxin and endotoxin) 77 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  This is only to ensure you are aware of the importance of the structure for Pharmacology in your senior years. You do not have to understand the Copyright © McGraw-Hill Education. Permission required for reproduction or display. MOA now. 4. Protein synthesis inhibitors acting 1. Cell wall inhibitors on ribosomes Block synthesis and repair Ribosome Penicillins Site of action Cephalosporins 50S subunit Vancomycin Chloramphenicol Bacitracin Erythromycin Monobactams/carbapenems Clindamycin Fosfomycin Streptogramin (Synercid) Cycloserine Isoniazid Substrate Site of action 30S subunit 2. Cell membrane Enzyme Aminoglycosides Cause loss of selective permeability Gentamicin Product Polymyxins Streptomycin Tetracyclines 3. DNA/RNA Both 30S and 50S Inhibit replication and transcription Inhibit gyrase (unwinding enzyme) Blocks initiation of protein Quinolones (ciprofloxacin) Synthesis Inhibit RNA polymerase Linezolid (Zyvox) Rifampin mRNA DNA 5. Metabolic pathways and products Block pathways and inhibit Metabolism Sulfonamides (sulfa drugs) 78 Trimethoprim Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Faecal Contamination Typhoid Fever (a) Typhoid bacilli Salmonella typhi – most serious pathogen of the genus; cause of typhoid fever; human host Intestinal Villi x500 Bacteria enters with ingestion of fecally contaminated food or water; occasionally spread by close (b) Blood vessels personal contact Carried to liver, spleen Intestinal wall Pathogens adhere to small intestine, cause invasive diarrhea that leads to septicemia Ulcers (c) Perforations