MIC 252 Bacterial Pathogenesis- An Overview (Attachment, Colonization and Multiplication)

1. MIC 252 Bacterial Pathogenesis- An Overview (Attachment, Colonization and Multiplication) Raymond Daniels x 2750 radaniels@uwc.ac.za

2. Definitions • Disease (dis-ease): • is an abnormal state in which part or all of the body is not properly adjusted or is incapable of performing normal functions • is an impairment of health or a condition of abnormal functioning • Disturbed homeostasis • Infection: • is the invasion and growth of pathogens in the body with or without disease • Infectious disease: • a clinically manifesting disease of humans or animals resulting from an infection • Pathogens: • microorganisms capable of causing disease • Pathogenicity: • ability of an infectious agent (pathogen) to cause disease by overcoming the defenses of a host

3. Definitions • Host: • an organism that shelters and supports the growth of a pathogen • Virulence: • the degree of pathogenicity • Toxigenicity: • the ability of a microorganism to produce a toxin that contributes to the development of disease • Spreading Factors: • is a descriptive term for a family of bacterial enzymes that affect the physical properties of tissue matrices and intercellular spaces, thereby promoting the spread of the pathogen

4. Pathogenesis of Bacterial Infection • Includes initiation of the infectious process and the mechanisms that lead to the development of signs and symptoms of the disease • Characteristics of bacteria that are pathogens include transmissibility, adherence to host cells and tissues, toxigenicity and the ability to evade the hosts defenses

5. Challenges that pathogens face in order to survive Maintain a reservoir in which it can survive before and after infection Leave its reservoir and enter the body of a human host (transmission- revise how diseases can be transmitted) Adhere (attach)firmly to the host’s body and thereby colonize it Invade the body in order to enter cells or deeper tissues Evade the host’s elaborate defenses Multiply within the body, perhaps producing toxic products or stimulating host reactions that cause disease Leave the body and return to the reservoir and/or enter a new host

6. Prokaryotic and Eukaryotic Interactions Eukaryotic Cell Prokaryotic Cell Pili or adhesins Intracellular Control of virulence factors:(Pilin, capsule, invasins, toxins etc) Virulent Bacteria Adherence blockers Receptor INVASION COLONIZATION

7. Disease Classification A patient may exhibit symptoms (subjective changes in body functions) and signs (measurable changes), which are used by a physician to make a diagnosis (identification of the disease). A specific group of symptoms or signs that always accompanies a specific disease is called a syndrome. Communicable diseases are transmitted directly or indirectly from one host to another. A contagious disease is one that is easily spread from one person to another. Noncommunicable diseases are caused by microorganisms that normally grow outside the human body and are not transmitted from one host to another.

8. Disease Occurrence • Disease occurrence is reported by incidence (number of people contracting the disease during a specified period of time) and prevalence (number of cases at a particular time) • Diseases are classified by frequency of occurrence: sporadic, endemic, epidemic, and pandemic Severity of Disease • The scope of a disease can be defined as acute, chronic, sub-acute, or latent

9. Disease Development The incubation period is the time interval between the initial infection and the first appearance of signs and symptoms The prodromal period is characterized by the appearance of the first mild signs and symptoms During the period of illness, the disease is at its height and all disease signs and symptoms are present During the period of decline, the signs and symptoms decrease During the period of convalescence, the body returns to its pre-diseased state, and health is restored

10. Bacteria that cause disease • Abundant normal flora that usually do not produce disease  achieved a balance that ensures the survival, growth and propagation of both bacteria and host • Bacteria can therefore be either pathogens, opportunistic pathogens or nonpathogens • Mycobacterium tuberculosis and Yersinia pestis are always considered as pathogens • Some bacteria are part of the normal flora and sometimes cause disease- e.g., E.coli • Other bacteria e.g., pseudomonas species only cause disease in immune suppressed and debilitated hosts opportunistic pathogens

11. Transmission of Infection • Bacteria adapt to the environment where they normally reside  ensures their survival and enhance possibility of transmission • By producing asymptomatic infection or mild disease that does not kill the host • Some bacteria e.g., salmonella and campylobacter species exist primarily in animals and incidentally infect humans • Some produce infection that are inadvertent (mistake)  organism has not adapted to humans and the disease is often severe or fatal • e.g., Y.pestis that lives in rodents and rodent fleas  fleas bite humans... • Bacillus anthracis lives in environment  occassionally infects animals and is transmitted to humans from raw hair of infected animals • Clostridium species e.g., C.perfringens gastroenteritis and C.botulinum are transmitted to humans through ingestion or contamination of open wounds

12. Transmission of Infection • Clinical manifestations produced by microorganisms are often necessary to promote transmission • E.g., V.cholerae and M.tuberculosis •  • Transmission by direct contact involves close physical contact between the source of the disease and a susceptible host. • Transmission by fomites (inanimate objects) constitutes indirect contact. • Transmission via saliva or mucus in coughing or sneezing is called droplet transmission. • Transmission by a medium such as water, food, or air is called vehicle transmission. • Airborne transmission refers to pathogens carried on water droplets or dust for a distance greater than one meter. • Arthropod vectors carry pathogens from one host to another by both mechanical and biological transmission

13. Portals of Entry • The specific route by which a particular pathogen gains access to the body is called its portal of entry • Portals of Entry: • 1. Many microorganisms can penetrate mucous membranes of the conjunctiva and the respiratory, gastrointestinal, and genitourinary tracts • 2. Microorganisms that are inhaled with droplets of moisture and dust particles gain access to the respiratory tract • 3. The respiratory tract is the most common portal of entry 4. Microorganisms enter the gastrointestinal tract by ingestion via food, water, and contaminated fingers 5. Most microorganisms cannot penetrate intact skin, but may enter hair follicles or sweat ducts

14. Portals of Entry 7. Some fungi infect the skin itself 8. Some microorganisms can gain access to tissues by direct penetration (inoculation) through the skin and mucous membranes in bites, injections, and other wounds. This route of penetration is called the parenteral route Many organisms can cause infections only when they gain access through their specific portal of entry Portals of Exit • Just as pathogens have preferred portals of entry, they also have definite portals of exit • Three common portals of exit are the respiratory tract via coughing or sneezing, the gastrointestinal tract via saliva or feces, and the urogenital tract via secretions from the vagina or penis • Arthropods and syringes provide a portal of exit for microbes in blood

15. Infectious Process • Once inside the body  bacteria must adhere to host cells, usually epithelial cells • After establishing a primary site of infection  multiply and spread directly through tissues or via the lymphatic system to the bloodstream • E.g., V.cholerae  ingestion and chemotactic attraction to the gut epithelium  motility via a single flagellum and penetration of the mucous layer on the intestinal surface  adherence to the epithelium is mediated by pili and possibly other adhesins  toxin production leads to flow of water and chloride into the gut  diarrhoea

16. Bacterial Virulence Factors • Genes for virulence factors are carried on plasmids or on phages • Environmental factors often cause the expression of these virulence genes • E.g., toxin production by C.diphtheriae is enhanced when the organism grow in low iron environments • Virulence gene expression of B.pertussis is enhanced when the organism grows at 37 degrees C Adherence • Many bacteria have surface structures necessary for attachment such as: • Pili • Capsules • Lipopolysaccharide

17. Factors that play a role in adhesion Surface hydrophobicity- the more hydrophobic the bacterial cell surfaces, the greater the adherence to the host cell. Different strains of bacteria within a species may vary widely in their hydrophobic surface properties and ability to adhere to host cells Net surface charge- bacteria & host cells have net neg. surface charges & thus repulsive electrostatic forces Overcome by hydrophobic & other interactive forces Bacterial surface molecules e.g., pili. Bacterial strains that lose their ability to produce pili become avirulent Other specific ligand-receptor mechanisms e.g., S.pyogenes. -Lipoteichoic acid- adherence is mediated by the lipid portion which acts as the ligand. -Fibronectin- host cell receptor molecule. -M protein on fimbriae- antiphagocytic molecule.

18. Terms used to describe adherence factors • Adhesin: A surface structure/macromolecule that binds a bacterium to a specific surface. • Receptor: A complementary macromolecular binding site on a (eukaryotic) surface that binds specific adhesins or ligands. • Lectin: Any protein that binds to a carbohydrate. • Ligand: A surface molecule that exhibits specific binding to a receptor molecule on another surface • Mucous: The mucopolysaccharide layer of glucosaminoglycans covering animal cell mucosal surfaces. • Fimbriae: Filamentous proteins on the surface of bacterial cells that may behave as adhesins for specific adherence. • Common pili: Same as fimbriae. • Sex pilus: A specialized pilus that binds mating procaryotes together for the purpose of DNA transfer.

19. Terms used to describe adherence factors • Type 1 fimbriae: Fimbriae in Enterobacteriaceae which bind specifically to mannose terminated glycoproteins on eukaryotic cell surfaces. • Glycocalyx: A layer of exopolysaccharide fibers on the surface of bacterial cells which may be involved in adherence to a surface. • Capsule: A detectable layer of polysaccharide (rarely polypeptide) on the surface of a bacterial cell which may mediate specific or nonspecific attachment. • Lipopolysaccharide (LPS): A distinct cell wall component of the outer membrane of Gram-negative bacteria with the potential structural diversity to mediate specific adherence. Probably functions as an adhesin. • Teichoic acids and lipoteichoic acids (LTA): Cell wall components of Gram-positive bacteria that may be involved in nonspecific or specific adherence

20. Invasion of Host Cells and Tissues • After adherence, pathogens invade and colonize the host by traversing the epithelium and its basement membrane at the body surface • Some invade tissues through the junctions between epithelial cells • Others invade the cells and so enter the tissue • However, invading microbes face the following defences: • tissue fluids containing antimicrobial substances (antibody, complement); • local macrophages (histiocytes). Subcutaneous and submucosal macrophages are a threat to microbial survival • the physical barrier of local tissue structure. Local tissues consist of various cells in a hydrated gel matrix; although viruses can spread by stepwise invasion of cells, invasion is more difficult for bacteria, and those that spread effectively sometimes possess special spreading factors (more detail later on); • the lymphatic system which conveys microorganisms to the battery of phagocytic and immunologic defenses awaiting them in the local lymph node

21. Spreading Factors • "Spreading Factors" is a descriptive term for a family of bacterial enzymes that affect the physical properties of tissue matrices and intercellular spaces, thereby promoting the spread of the pathogen. • Hyaluronidase is the original spreading factor  produced by streptococci, staphylococci, and clostridia  attacks the interstitial cement ("ground substance") of connective tissue by depolymerising hyaluronic acid • Collagenase is produced by Clostridium histolyticum and Clostridium perfringens breaks down collagen, the framework of muscles, which facilitates gas gangrene • Neuraminidase is produced by intestinal pathogens such as Vibrio cholerae and Shigella dysenteriae  degrades neuraminic acid (also called sialic acid), an intercellular cement of the epithelial cells of the intestinal mucosa

22. Spreading Factors • Streptokinase and Staphylokinase are produced by streptococci and staphylococci, respectively  converts inactive plasminogen to plasmin digests fibrin  prevents clotting of blood  relative absence of fibrin in spreading bacterial lesions allows more rapid diffusion of the infectious bacteria • Staphylococcal coagulase  cell-associated and diffusible enzyme  converts fibrinogen  fibrin  causes clotting • Coagulase activity is almostalways associated with pathogenic S. aureus and almost never with non-pathogenic S. epidermidis. • I.t.o. virulence, cell bound coagulase could provide an antigenic disguise if it clotted fibrin on the cell surface. • Alternatively, staphylococcal lesion encased in fibrin (e.g. a boil or pimple) could make the bacterial cells resistant to phagocytes or tissue bactericides or even drugs (antibiotics) which might be unable to diffuse to their bacterial target.

23. Spreading and Systemic Infections • As can be seen pathogens are adapted to attach, colonize and invade their target tissues/organs • In the next lecture we will focus on how pathogens goes about spreading in the host and causing systemic infections