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

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 Disease Occurrence The scope of a disease can be defined as acute, chronic, sub-acute, or latent Severity of Disease

1. The incubation period is the time interval between the initial infection and the first appearance of signs and symptoms 2. The prodromal period is characterized by the appearance of the first mild signs and symptoms 3. During the period of illness, the disease is at its height and all disease signs and symptoms are present 4. During the period of decline, the signs and symptoms decrease 5. During the period of convalescence, the body returns to its pre- diseased state, and health is restored Disease Development

A.Definitions w Pathogenicity and Virulence Pathogenicity The ability of a microbe to cause disease This term is often used to describe or compare species Virulence The degree of pathogenicity in a microorganism This term is often used to describe or compare strains within a species

Classification of infection w Acute infection vs. chronic infection Acute Infection An infection characterized by sudden onset, rapid progression, and often with severe symptoms Chronic Infection An infection characterized by delayed onset and slow progression

Classification of infection w Primary infection vs. secondary infection Primary Infection An infection that develops in an otherwise healthy individual Secondary Infection An infection that develops in an individual who is already infected with a different pathogen

Classification of infection w Localized infection vs. systemic infection Localized Infection An infection that is restricted to a specific location or region within the body of the host Systemic Infection An infection that has spread to several regions or areas in the body of the host

Classification of infection w Clinical infection vs. subclinical infection Clinical Infection An infection with obvious observable or detectable symptoms Subclinical Infection An infection with few or no obvious symptoms

Definitions w Opportunistic infection An infection caused by microorganisms that are commonly found in the host’s environment. This term is often used to refer to infections caused by organisms in the normal flora.

Classification of infection w The suffix “-emia” A suffix meaning “presence of an infectious agent” Bacteremia = Presence of infectious bacteria Viremia = Presence of infectious virus Fungemia = Presence of infectious fungus Septicemia = Presence of an infectious agent in the bloodstream

Classification of infection w The suffix “-itis” A suffix meaning “inflammation of” Examples: –Pharyngitis = Inflammation of the pharynx –Endocarditis = Inflammation of the heart chambers –Gastroenteritis = Inflammation of the gastointestinal tract

Classification of infection w Epidemiology The study of the transmission of disease w Communicable Disease A disease that can be transmitted from one individual to another w Noncommunicable Disease A disease that is not transmitted from one individual to another

Classification of infection w Endemic Disease A disease condition that is normally found in a certain percentage of a population w Epidemic Disease A disease condition present in a greater than usual percentage of a specific population w Pandemic Disease An epidemic affecting a large geographical area; often on a global scale

Source of infection w Reservoir of Infection The source of an infectious agent w Carrier An individual who carries an infectious agent without manifesting symptoms, yet who can transmit the agent to another individual w Fomites Any inanimate object capable of being an intermediate in the indirect transmission of an infectious agent

Transmission of disease Animal Vectors An animal (nonhuman) that can transmit an infectious agent to humans Two types: mechanical and biological Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow in the animal; e.g, the transmission of bacteria sticking to the feet of flies Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; e.g, the transmission of malaria by infected mosquitoes

Transmission of disease w Direct Mechanisms of Disease Transmission Directly From Person to Person Examples: Direct Skin Contact Airborne (Aerosols)

Transmission of disease w Indirect Mechanisms of Disease Transmission Examples: Food & Waterborne Transmission Fomites Animal Vectors

Pathogenicity - ability to cause disease Virulence - degree of pathogenicity w Many properties that determine a microbe’s pathogenicity or virulence are unclear or unknown w But, when a microbe overpowers the hosts defenses, infectious disease results!

Molecular Determinants of Pathogenicity Production and delivery of various factors Attachment to host tissues Replication and evasion of immunity Damage to host tissues

Microbial Mechanisms of Pathogenicity: How Microorganisms Cause Disease

Portals of Entry w 1. Mucus Membranes w 2. Skin w 3. Parentarel

1. Mucus Membranes w A. Respiratory Tract microbes inhaled into mouth or nose in droplets of moisture or dust particles Easiest and most frequently traveled portal of entry

Common Diseases contracted via the Respiratory Tract w Common cold w Flu w Tuberculosis w Whooping cough w Pneumonia w Measles w Diphtheria

Mucus Membranes w B. Gastrointestinal Tract microbes gain entrance thru contaminated food & water or fingers & hands most microbes that enter the G.I. Tract are destroyed by HCL & enzymes of stomach or bile & enzymes of small intestine

Common diseases contracted via the G.I. Tract w Salmonellosis Salmonella sp. w Shigellosis Shigella sp. w Cholera Vibrio cholorea w Ulcers Helicobacter pylori w Botulism Clostridium botulinum

Fecal - Oral Diseases w These pathogens enter the G.I. Tract at one end and exit at the other end. w Spread by contaminated hands & fingers or contaminated food & water w Poor personal hygiene.

Mucus Membranes of the Genitourinary System - STD’s Gonorrhea Neisseria gonorrhoeae Syphilis Treponema pallidum Chlamydia Chlamydia trachomatis HIV Herpes Simplex II

Mucus Membranes w D. Conjunctiva – mucus membranes that cover the eyeball and lines the eyelid w Trachoma Chlamydia trachomatis

2nd Portal of Entry: Skin w Skin - the largest organ of the body. When unbroken is an effective barrier for most microorganisms. w Some microbes can gain entrance through openings in the skin: hair follicles and sweat glands, wound …etc

3rd Portal of Entry: Parentarel w Microorganisms are deposited into the tissues below the skin or mucus membranes w Punctures and scratches w injections w bites w surgery

Preferred Portal of Entry w Just because a pathogen enters your body it does not mean it’s going to cause disease. w pathogens - preferred portal of entry

Preferred Portal of Entry w Streptococcus pneumoniae if inhaled can cause pneumonia if enters the G.I. Tract, no disease w Salmonella typhi if enters the G.I. Tract can cause Typhoid Fever if on skin, no disease

Number of Invading Microbes w LD 50 - Lethal Dose of a microbes toxin that will kill 50% of experimentally inoculated test animal w ID 50 - infectious dose required to cause disease in 50% of inoculated test animals Example: ID 50 for Vibrio cholerea 10 8 cells (100,000,000 cells) ID 50 for Inhalation Anthrax - 5,000 to 10,000 spores ????

How do Bacterial Pathogens penetrate Host Defenses? 1. Adherence - almost all pathogens have a means to attach to host tissue Binding Sites adhesins ligands

Some cells use fimbriae to adhere. Fimbriae can play a role in tissue tropism. Example - attachment of Candida to vaginal epithelial cells

Adhesins and ligands are usually on Fimbriae w Neisseria gonorrhoeae w ETEC (Entertoxigenic E. coli) w Bordetello pertussis

Bacteria typically employ proteins known as Adhesins to attach to host tissues, which usually are located on ends of fimbriae. Alternatively, adhesins can consist of glycocalyx.

2. Capsules w Prevent phagocytosis w attachment w Streptococcus pneumoniae w Klebsiella pneumoniae w Haemophilus influenzae w Bacillus anthracis w Streptococcus mutans K. pneumoniae

Avoidance of Phagocytosis Capsules are Involved in avoidance of phagocyte- mediated recognition and attachment.

Cell Wall Components M protein: Found on cell surface and fimbriae of Streptococcus pyogenes. Mediates attachment and helps resist phagocytosis. M-protein is heat and acid resistant Waxes [ Mycolic Acid]: In cell wall of Mycobacterium tuberculosis helps resist digestion after phagocytosis and can multiply inside WBC.

3. Enzymes w Many pathogens secrete enzymes that contribute to their pathogenicity

Enzymes and toxins that harm eukaryotic cells.

A. Leukocidins w Attack certain types of WBC’s w 1. Kills WBC’s which prevents phagocytosis w 2. Releases & ruptures lysosomes lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage

B. Hemolysins - cause the lysis of RBC’s Streptococci

1. Alpha (α) Hemolytic Streptococci - secrete hemolysins that cause the incomplete lysis or RBC’s Incomplete Lysis of RBC

2. Beta (β) Hemolytic Streptococci - secrete hemolysins that cause the complete lysis of RBC’s Complete Lysis of RBC

3. Gamma (γ) Hemolytic Streptococci - do not secrete any hemolysins

C. Coagulase - cause blood to coagulate w Blood clots protect bacteria from phagocytosis from WBC’s and other host defenses w Staphylococcus aureus - are often coagulase positive Fibrinogen Fibrin ( Clot)

D. Kinases - enzymes that dissolve blood clots w 1. Streptokinase - Streptococci w 2. Staphylokinase - Staphylococci w Helps to spread bacteria - Bacteremia w Streptokinase - used to dissolve blood clots in the Heart (Heart Attacks due to obstructed coronary blood vessels)

E. Hyaluronidase w Breaks down Hyaluronic acid (found in connective tissues) w “Spreading Factor” w mixed with a drug to help spread the drug through a body tissue w Streptococci, Staphylococci, Clostridia and pneumococci.