Chapter 30 Pathogenicity of Microorganisms

Host-Parasite Relationships Symbiosis the “living together” of two organisms in a variety of relationships commensalism mutualism parasitism Saprophytic organisms obtain nutrients from dead or decaying organic matter some are pathogenic but most are considered scavengers

Parasites Parasites are organisms that live on or within a host organism and are metabolically dependent on the host types of parasites ectoparasite lives on surface of host endoparasite lives within host

Types of Hosts Final host host on (or in) which parasite either gains sexual maturity or reproduces Intermediate host serves as temporary but essential environment for some stage of parasite’s development Transfer host is not necessary for development but serves as vehicle for reaching final host Reservoir host nonhuman organism infected with a parasite that can also infect humans

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 Factors: number of organisms present the degree of virulence of pathogen virulence factors e.g., capsules, pili, toxins host’s defenses or degree of resistance

Table 30.1

Figure 30.1 Mathematical Expression of Infection

Virulence 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

Measuring Virulence Lethal dose 50 (LD 50 ) number of pathogens that will kill 50% of an experimental group of hosts in a specified time Infectious dose 50 (ID 50 ) number of pathogens that will infect 50% of an experimental group of hosts in a specified time

Figure 30.2:Determination of LD 50 Strain A LD 50 is 30, B LD 50 is 50 hence, A is more virulent.

Pathogenesis of Viral Diseases Fundamental process of Viral infection in a host cell: maintain reservoir –a place to live and multiply before infection enter host contact and enter susceptible cells replicate within cells release from host (immediate or delayed)

…Viral infection spread to adjacent cells Evade host immune response be cleared from body of host, establish persistent infection, or kill host be shed back into environment

Maintaining a Reservoir 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 attachment to the cell surface results from binding of viral protein to host cell receptors binding of virus to receptor results in cell penetration or delivery of viral nucleic acid to host cell cytoplasm

Entry of Human Virus Nucleic Acids into Host Cell Direct entry of nucleic acid e.g., polio virus- enters the host cell and deliver viral nucleic acid into the cytoplasm of cell It enters through the human gastrointestinal tract but produces diseases in the central nervous system. endocytosis and release of nucleic acid from capsid (uncoating) e.g., pox viruses- causes small pox Fusion of viral envelope e.g. influenza –fusion of viral envelope with cell membrane of host

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 tract but produce disease in central nervous system

Evasion of Host Defenses begins when the virus first infects the host for the virus to cause a successful infection, it must be able to avoid host immunity so it can spread to a sufficient number of host cells to amplify the number of virions

Viral Spread and Cell Tropism Viral spread vary but most common is by bloodstream and lymphatic system Viremia- presence of virus in blood Spread by way of nerves e.g rabies Tropisms Viruses exhibit cell, tissue, and organ specificities

Virus-Host Interactions Cytopathic viruses local necrosis with ultimate host death alternatively, can trigger apoptosis (programmed cell death) i.e host cell dies, often before viral replication can occur Noncytopathic viruses cause latent or persistent infections

…Non-Cytopathic Viruses Do not immediately cause cell death cause latent or persistent infections productive non-cytopathic viruses produce persistent infection with the release of only a few new particles at a time nonproductive non-cytopathic viruses do not actively make virus at detectable levels for a period of time (latent infection) these viruses may become productive by environmental stressors or other factors

Other Outcomes of Virus-Host Interaction Clinical illness some tissues can be quickly repaired after viral damage e.g., intestinal epithelium others cannot be easily repaired e.g., tissues of central nervous system Integration of viral DNA may result in transformation of host cells into cancerous cells due to viral DNA interference with host DNA growth cycle regulation

…Virus Shedding last step in infectious process is shedding of the virus in the environment needed for maintenance of viral source in a host population often occurs at same body surface used for entry of the virus at this stage host is very contagious/infectious/stay far…..can spread in some infections, host is dead (end of host) and no shedding occurs-e.g Rabies

Pathogenesis of Bacterial Diseases Maintain a reservoir Like viral infection Bacteria too need a place to live before and after causing infection initial transport to/entry into host adhere to, colonize, and/or invade host

…Bacterial infection 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 structures: Structures such as such as pili and fimbriae and specialized adhesion molecules on bacterium’s cell surface bind to complementary receptor sites on host cell surface Colonization: Colonization is the establishment of a site of microbial reproduction on or within host does not necessarily result in tissue invasion or damage

Evasion of Host Defenses by Bacteria Successful pathogens can evade destruction by host : by: Formation of capsule- Neisseria gonorrhoeae production of leukocidins- substance that destroy phagocytes before phagocytosis can occur – Streptoccocus pneumoniae, Staphyloccocus use of an actin tail (cytoskeleton protein) to spread into neighboring cells and escape destruction e.g Shigella Lysosomal enzymes- Mycobacterium tuberculosis resist these enzymes probably because of itd waxy external layer.

Endotoxins Table 30.4-Bacterium polymerised host actin into long tail and for propulsion from one cell to another and out of the host.

Bacterial Invasiveness Varies among pathogens e.g., Clostridium tetani (tetanus) produces a number of virulence factors (e.g toxin and proteolytic enzymes ) but is non-invasive i.e it does not spread from one tissue to another. e.g., Bacillus anthracis (anthrax) and Yersinia pestis (plague) also produce many virulence factors ( capsule & toxins) and are highly invasive e.g., Streptococcus spp. span the spectrum of virulence factors and invasiveness

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 Bacteria that are able to grow and multiply in various cells of a host Facultative intracellular pathogens can live within host cells or in the environment e.g., Brucella abortus can grow independently as well as in macrophages, neutrophils and trophoblast cells Obligate intracellular pathogens incapable of growth and multiplication outside of a host eg., viruses and rickettsia

Leaving the Host must occur if microbe is to be perpetuated most bacteria leave by passive mechanisms in feces, urine, droplets, saliva

Regulation of Bacterial Virulence Factor Expression Often environmental factors control expression of virulence genes e.g., Corynebacterium diphtheriae gene for diphtheria toxin regulated by iron e.g., Bordetella pertussis expression of virulence genes increased at body temperature e.g., Vibrio cholerae gene for cholera toxin regulated by pH, temperature and other factors

Pathogenicity Islands Pathogenicity Islands- large segments of DNA that carry virulence genes acquired during evolution of pathogen by horizontal gene transfer e.g., genes for type III secretion system (TTSS) enables gram-negative bacteria to secrete and inject virulence proteins into cytoplasm of eucaryotic host

Toxigenicity Intoxications diseases that result from entry of a specific preformed toxin into host Toxin specific substance that damages host two main categories in bacteria exotoxins endotoxins Toxemia condition caused by toxins in the blood of host

Exotoxins Exotoxins - soluble, heat-labile, proteins and usually released into the surroundings as bacterial pathogen grows humans exposed to exotoxins in three main ways ingestion of preformed exotoxin bacterial colonization of a mucosal surface followed by exotoxin production colonization of a wound or abscess followed by local exotoxin production most exotoxin producers are gram-positive often travel from site of infection to other tissues or cells where they exert their effects

Types of Exotoxins AB exotoxins- composed of two subunits A subunit – responsible for toxic effect once inside the host cell B subunit – binds to target cell od host specific host site exotoxins-e.g neurotoxin membrane- disrupting exotoxinspore- e.g forming exotoxins Superantigens (enterotoxin of staph) that stimulate T cells directly to make cytokines

AB Exotoxins Composed of two subunits A subunit – responsible for toxic effect once inside the host cell B subunit – binds to target cell

Specific Host Site Exotoxins can be AB toxins neurotoxins target nerve tissue e.g., botulinum toxin enterotoxins target intestinal mucosa e.g., cholera toxin cytotoxins target general tissues e.g., nephrotoxin

Membrane-Disrupting Exotoxins do not have separable A and B subunits two types pore-forming exotoxins Phospholipases-lyses the plasma membrane e.g- Clostridium perfringens-gas gagresn

Some Pore-Forming Exotoxins Bacterial Toxins that forms pores in the membranes: Leukocidins –membrane-disrupting toxins kill phagocytic leukocytes- pneumococci. Strepto, staphyloccus Hemolysins- other toxin that form pores in membranes of blood cells kill erythrocytes, leukocytes, and many other cells e.g., streptolysin-O (SLO)- a hemolysin from Streptococcus pyogenes- oxygen-sensitive e.g., streptolysin-S (SLS)- oxygen-stable

Hemolytic Reactions beta-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 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 cell death

Endotoxins Lipopolysaccharide (LPS) in gram-negative outer membrane 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

Polymicrobial Diseases Polymicrobial Diseases -many infectious diseases involve the interactions of more than one infectious agent these diseases can be polyviral, polybacterial, combined viral-bacterial, or polymycotic or protozoan Dental infections are examples of polybacterial disease

Dental Infections Dental Infections -caused by various odontopathogens Formation of dental plaque creates environment for pathogens that produce acids and other virulence factors

Figure 30.9: Plaque Development Process

Figure Microscopic Appearance of Plaque

Periodontal Disease… Periodontitis initial inflammatory response to plaque bacteria and tissue destruction leads to swelling of tissue and formation of periodontal pockets Periodontosis bone destruction caused by colonization of periodontal pockets

Periodontal Disease… Gingivitis inflammation of gingiva caused by colonization of periodontal pockets Treatment, prevention, and control oral surgery and antibiotic therapy in some cases plaque removal and good dental hygiene

Bibliography Lecture PowerPoints Prescott’s Principles of Microbiology-Mc Graw Hill Co. method method rix/bio3340/home.html rix/bio3340/home.html