Pathogenicity of Microorganisms Chapter 33 Pathogenicity of Microorganisms

Parasitism and disease infection growth and multiplication of parasite on or within host infectious disease disease resulting from infection pathogen any parasitic organism that causes infectious disease primary (frank) pathogen – causes disease by direct interaction with healthy host opportunistic pathogen – part of normal flora and causes disease when it has gained access to other tissue sites or host is immunocompromised pathogenicity ability of parasite to cause disease

Factors impacting outcome of host-parasite relationships number of organisms present the degree of virulence of pathogen virulence factors e.g., capsules, pili, toxins host’s defenses or degree of resistance

Virulence degree or intensity of pathogenicity determined by three characteristics of the pathogen invasiveness ability to spread to adjacent tissues infectivity ability to establish focal point of infection pathogenic potential degree to which pathogen can cause damage to host

Aspects of pathogenic potential toxigenicity ability to produce toxins immunopathology ability to trigger exaggerated immune responses

Pathogenesis of Viral Diseases maintain reservoir enter host contact and enter susceptible cells replicate within cells release from host (immediate or delayed) spread to adjacent cells engender host immune response be cleared from host, establish persistent infection, or kill host be shed back into environment

Maintaining a Reservoir Where do they live before they are transmitted? most common reservoir of human viruses are humans and other animals some viruses are acquired early in host’s life and cause disease later most often, viruses are transmitted from one host to another host and cause infection in a short time frame

Viral Entry occurs at a variety of sites via body surface via sexual contact, needle sticks, blood transfusions, and organ transplants via insect vectors organisms that transmit pathogen from one host to another

Adsorption adsorption attachment to the cell surface results from binding of viral protein ligands to host cell receptors binding of virus to receptor results in cell penetration or delivery of virtal nucleic acid to host cell cytoplasm

Entry of Human Virus Nucleic Acids into Host Cell direct entry of nucleic acid e.g., polio virus endocytosis and release of nucleic acid from capsid (uncoating) e.g., pox viruses fusion of viral envelope with cell membrane and subsequent uncoating e.g. influenza

Primary Replication primary replication some replicate at site of entry, cause disease at same site, and do not spread throughout body others spread to distant sites and then replicate e.g., polio viruses enter through gastrointestinal track but produces disease in central nervous system

Release from Host Cells host cell lysis replication of viral particles increases within host cell until cell membrane cannot contain all the material within results in large number of viral particles released at the same time budding or “blebbing” replicated viral particle becomes enclosed in host cell membrane which is then called the viral envelope release of viral particles is a slower process than lysis

Viral Spread and Cell Tropism usually spread by blood stream and lymphatic system viremia presence of virus in blood tropisms cell, tissue, and organ specificities

Pathogenesis of Bacterial Diseases maintain a reservoir place to live before and after causing infection initial transport to/entry into host adhere to, colonize, and/or invade host initially evade host defenses multiply or complete life cycles on or in host damage host leave host and return to reservoir or enter new host

Maintaining a Reservoir of the Bacterial Pathogen for human pathogens, most common reservoirs are: other humans animals environment

Transport of the Bacterial Pathogen to the Host direct contact e.g., coughing, sneezing, body contact indirect contact vehicles (e.g., soil, water, food) Arthropod vectors fomites – inanimate objects that harbor and transmit pathogens

Attachment and Colonization by the Bacterial Pathogen adherence mediated by special molecules or structures called adhesins colonization establishment of a site of microbial reproduction on or within host does not necessarily result in tissue invasion or damage

Attachment and Colonization by the Bacterial Pathogen adherence structures such as pili and fimbriae and specialized adhesion molecules on bacterium’s cell surface bind to complementary receptor sites on host cell surface are a type of virulence factor colonization establishment of a site of microbial reproduction on or within host does not necessarily result in tissue invasion or damage

fimbriae TEM of fimbriated E. coli. Figure 33.3 (a)

Invasion of the Bacterial Pathogen can be active penetration of host’s mucous membranes or epithelium can be passive penetration e.g., skin lesions, insect bites, wounds once below mucous membrane, bacterium can spread to deeper tissues involves production of specific products and/or enzymes that promote spreading

Bacterial Invasiveness varies among pathogens e.g., Clostridium tetani (tetanus) produces a number of virulence factors but is non-invasive e.g., Bacillus anthracis (anthrax) and Yersinia pestis (plague) also produce many virulence factors and are highly invasive

Growth and Multiplication of the Bacterial Pathogen occurs when pathogen finds appropriate environment within host some pathogens actively grow in blood plasma bacteremia – presence of viable bacteria in blood septicemia – presence of bacteria or their toxins in blood

Intracellular Pathogens obligate intracellular pathogens incapable of growth and multiplication outside of a host eg., viruses and rickettsia

Leaving the Host most bacteria leave by passive mechanisms in feces, urine, droplets, saliva,

Toxigenicity intoxications toxin toxemia diseases that result from entry of a specific preformed toxin into host toxin specific substance that damages host toxemia condition caused by toxins in the blood of host

Toxigenicity intoxications toxin toxemia diseases that result from a specific toxin produced by bacteria. Some toxins are only produced during host infection toxin specific substance that damages host toxemia condition caused by toxins in the blood of host

Exotoxins soluble, heat-labile, proteins usually released into the surroundings as bacterial pathogen grows most exotoxin producers are gram-negative often travel from site of infection to other tissues or cells where they exert their effects

More About Exotoxins usually synthesized by specific bacteria that have toxin genes in their plasmids or prophage DNA Corynebacterium diphtheriae -diphtheria among the most lethal substances known are highly immunogenic can stimulate production of neutralizing antibodies (antitoxins) can be chemically inactivated to form immunogenic toxoids e.g., tetanus toxoid

Some pore-forming exotoxins leukocidins kill phagocytic leukocytes hemolysins kill erythrocytes, leukocytes, and many other cells e.g., streptolysin-O (SLO) oxygen-sensitive e.g., streptolysin-S (SLS) oxygen stable

Hemolytic reactions beta-hemolysis alpha-hemolysis complete lysis observed as zone of clearing around colony on blood agar alpha-hemolysis partial lysis observed as greenish zone around colony on blood agar

Phospholipase Enzymes a second subtype of membrane-disrupting toxins remove charged head group from lipid part of phospholipids in host-cell plasma membranes membrane destabilizes, cell lyses and dies Clostridium perfringens

Phospholipase Enzymes a second subtype of membrane-disrupting toxins remove charged head group from lipid part of phospholipids in host-cell plasma membranes membrane destabilizes, cell lyses and dies Clostridium perfringens

Figure 33.6 (b)

Endotoxins lipopolysaccharide in gram-negative cell wall can be toxic to specific hosts called endotoxin because it is bound to bacterium and released when organism lyses and some is also released during multiplication toxic component is the lipid portion, lipid A

More about Endotoxins heat stable toxic (nanogram amounts) weakly immunogenic generally similar, despite source cause general system weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis, the enzymatic breakdown of fibrin, themajor protein component of blood clots septic shock

Host Defense Against Microbial Invasion in host-pathogen relationships survival strategies have co-evolved host has many niches for microbes which adapt to the various environmental conditions present in the body host also has a variety of barriers to defend itself from microbial invasion

Figure 33.8

Primary Defenses to be effective, must limit bacterial entry without limiting essential functions of host e.g., skin has many layers with glands present that produce anti-microbial substances; normal flora also protect host e.g., mucous membranes with cilia e.g. pH regulation (skin slightly acidic) e.g., flushing mechanisms e.g., additional antimicrobial substances produced where host tissues interface with the environment

Secondary Defenses consists of soluble anti-microbial products, cells capable of sensing and responding to invading microbes and long-term memory host blood and interstitial fluids contain anti-microbial proteins processes such as complement activation, inflammation, fever and phagocytosis

Factors Influencing Host Defenses age, stress, nutritional deficiencies and genetic background can influence primary and secondary immune responses of host long-term exposure to environmental pollutants, drug abuse, or certain prescribed medicine can inhibit normal host defenses against infection

Microbial Mechanisms for Escaping Host Defenses numerous mechanisms for both viral and bacterial pathogens

Evasion of Host Defenses by Viruses mutations that change antigenic sites or alter expression of antigens infection of immune system cells, diminishing their function

Evasion of Host Defenses by Bacteria have mechanisms to resist complement system, phagocytosis, and specific immune responses

Evading the complement system capsules lengthened O-chains serum resistance modified lipooligosaccharides interfere with formation of membrane attack complex

Resisting phagocytosis capsules production of specialized surface proteins that block adherence of phagocytes to bacterium production of leukocidins that destroy phagocytes production of proteases that cleave complement factor C5a (phagocyte chemoattractant)