Bacteriology III: Normal Flora and Pathogens

Terminology

• Normal Flora: endogenous microorganisms that live on another living organism without causing disease
• Pathogen: an organism that can cause disease
• Opportunistic pathogen: non-pathogenic organisms that cause serious disease in immuno-compromised individuals or when in other locations
• Virulence Factors: bacterial features that contribute to infection
• Pathogenesis: the mechanism by which infections lead to symptoms

Normal Flora

• Consists of all microorganisms present in the body
• Microbiome refers to the microorganisms and their genes
• Microbiota refers to the microbes themselves
• Example: An adult human body has approximately 2 m2 of skin, and it contains about 10^12 numbers of bacteria
• Normal flora prevents the colonization of pathogens by competing with them for essential nutrients and attachment sites

Microbiome

• Initial colonization of bacteria occurs primarily in the first year of life
• A healthy microbiome is highly diverse with beneficial bacteria
• Microbiota vary in anatomic location and composition
• Example: Ubiquitous on the skin (e.g., Staphylococcus), very high numbers in the intestine (e.g., Escherichia coli), and absent in sterile sites (e.g., blood, organs)
• Loss of diversity leads to altered microbiota (dysbiosis) and is associated with many health conditions

Microbiome Impact in Health

• Example of dysbiosis: Clostridiodes difficile infection
• Dysbiosis may lead to infections, and fecal transplantation can be used to treat dysbiosis

Types of Infections

• Primary infection: Initial infection with an organism in the host
• Reinfection: Subsequent infection by the same organism in the host (after recovery)
• Secondary infection: An infection that follows on from, or is the indirect result of another infection
• Superinfection: Secondary infection that occurs during treatment of a primary infection
• Opportunistic infection (primary or secondary): caused by normally harmless bacteria that become pathogenic upon favorable changes in the environment

Infection

• Infection is dose-related
• Virulence factors contribute to the ability of a microorganism to cause disease

Virulence Factors

• Adhesion: attachment to host tissue or abiotic surfaces
• Invasion: penetration of host tissue
• Resistance to environment and host immunity: ability to survive and evade host defense mechanisms
• Secretion: release of exotoxins, enzymes, and effector proteins
• Virulence factors are molecules that enhance the ability of a microorganism to cause disease beyond that intrinsic to the species

Bacterial Appendages with Adhesin Properties

• Pili or fimbriae: thin thread-like structures with adhesin properties
• Mediate the attachment of bacteria to mucosal or other surfaces

Bacterial Adhesins

• Important for attachment to host tissue or abiotic surfaces
• Examples: FimH adhesin, Proanthocyanidins in cranberries

Bacterial Flagella

• Associated with motility
• Contributes to virulence by penetrating the mucus layer and aiding attachment
• Important for classification
• Recognized by the innate immune system

Bacterial Capsule

• Glycocalyx: a gelatinous sugar material including proteoglycans, glycoproteins, and glycolipids
• Functions to help the organism resist environmental insults and is anti-phagocytic
• Asplenic individuals are vulnerable to sepsis, as the majority of antibodies against the capsule are produced in the spleen

Capsules and the Immune System

• Non-encapsulated organisms are resistant to unenhanced phagocytosis
• Encapsulated organisms are resistant to phagocytosis and require antibodies and complement to be dealt with

Bacterial Endospores

• Formed during harsh environmental growth conditions
• Highly resistant to desiccation, chemicals, hot/cold temperatures, and radiation
• Found in the environment
• Germinate into vegetative (replicating) bacterial cells on contact with moisture and suitable temperature and pH

Bacterial Biofilm

• Bacteria are sheltered from harmful factors in the environment, such as desiccation, antibiotics, and a host body's immune system
• Slimy extracellular matrix produced by the bacteria
• Biofilm composed of extracellular polymeric substances (EPSs)

Bacterial Secretion Systems

• Secretion Systems: Found in several Gram-negative bacteria
• Important in the release of exotoxins, enzymes, and effector proteins
• Type 3 Secretion System (T3SS) acts as a "needle" to inject effector proteins into the host and modify host cellular characteristics

Bacterial Enzymes

• Enzymes to break down host tissues
• Examples: Hyaluronidase, Proteases, Lipases, DNAses, Hemolysins

Bacterial Toxins

• Exotoxins: produced by bacteria and secreted into the environment
• Types: A/B-toxins (Type III toxin), Membrane disrupting toxins (Type II toxin), Superantigens (Type I toxin)
• Examples: Cholera, Tetanus, Botulism

Exotoxin: A/B-type Toxin

• 2 Components: A "active" subunit and B "binding" subunit
• B-subunit binds to specific host cell receptor, leading to internalization
• A-subunit disassociates from B-subunit in host cell and targets cellular function

Exotoxin: Membrane disrupting toxin

• Cytotoxin secreted by bacteria from local infection
• Toxin acts by forming pores in host cell membrane
• Causes localized inflammation and damage

Exotoxin: Super-antigen (exotoxin)

• Non-specific activation of T cells leads to massive cytokine release, causing Toxic Shock
• Example: Staph aureus Toxic Shock Syndrome Toxin

Bacterial Toxins: Endotoxins

• Produced only on cell lysis (cell death)

• Lipopolysaccharide (LPS) components of the outer membrane of Gram-negative bacteria

• Endotoxins produce their effect in a host by activating the complement system by the alternative pathway

• Pyrogenic in action (i.e., they produce fever in their host)### Bacterial Toxins: Endotoxins

• Bacterial endotoxins can cause bacterial sepsis (shock) and intravascular coagulation, leading to conditions like meningococcemia and sepsis.

Pathogenicity: Multi-step Disease Process

• The disease process involves multiple steps, resulting in different outcomes, including acute, transient carrier, chronic latent, chronic persistent, and chronic recurrent.

Disease Process: Outcomes

• Acute: finite duration of time of infection and symptoms, resulting in resolution.
• Transient carrier: finite duration and absence of symptoms with low infections.
• Chronic latent: long duration of time and no display of symptoms of disease.
• Chronic persistent: long duration of time and continuous symptoms.
• Chronic recurrent: long duration of time and symptoms that exacerbate and abate, often due to changes in a person's immune status.

Bacterial Load

• The bacterial load affects the outcome of the disease process, with higher loads leading to more severe outcomes.
• The relationship between bacterial load and disease outcome is complex, with multiple factors influencing the progression of the disease.

This quiz covers the basics of bacteriology, including normal flora, pathogens, and opportunistic pathogens. Learn about the terminology and concepts related to microbiology.