Host-Microbe Interactions & Pathogenesis
10.1: Basics of Host-Microbe Interactions
Host-Microbe Interactions Are Not Always Harmful
Normal microbiota play crucial roles within the human body.
Colonize various systems: skin, digestive, genital, urinary, and respiratory.
In exchange for habitat, microbiota:
Manufacture essential vitamins.
Compete with potential pathogenic microorganisms.
Promote the maturation of the immune system.
Interactions can be mutualistic (beneficial) or commensal (neutral).
Disrupting the normal microbiota balance can lead to health issues.
This disruption is referred to as dysbiosis.
Example of dysbiosis: Antibiotic use can lead to Clostridium difficile infections.
Host factors might cause harmless microbial species to become pathogenic in certain individuals:
Example: Group B streptococci (GBS) infections:
Approximately 30% of women harbor commensal GBS in the vagina.
In newborns, GBS can be associated with sepsis, meningitis, and pneumonia.
Pregnant women are routinely screened for GBS due to its potential danger.
The immune system recognizes the presence of normal microbiota:
It mounts a moderate response, ensuring a balanced communication between the immune system and resident microbes.
Opportunistic pathogens may cause illness under specific circumstances:
Example: Escherichia coli can cause disease when it enters the abdominal cavity or when a person has a weakened immune system, potentially allowing yeast infections.
Tropism: The preference of a pathogen for a specific host or type of tissue within a host.
Examples include:
Human-only pathogens or gastrointestinal-only pathogens.
Pathogens demonstrate varying degrees of tropism; this characteristic may evolve over time.
Spillover events may cause emerging pathogens to expand their host or tissue range and successfully infect humans.
Even the successful colonization of a favored tissue by a pathogen does not always result in disease; numerous host factors influence disease development:
Factors include age, gender, overall health, and lifestyle habits.
10.2: Introduction to Virulence
Host-Microbe Interactions Influence Virulence
Pathogenicity: Refers to the ability of a microbe to cause disease, essentially identifying a microbe as pathogenic or not.
Virulence: The degree or extent to which a pathogen causes disease; compares the severity of different pathogens (e.g., colds vs. flu).
Virulence factors: Mechanisms that allow pathogens to overcome host defenses:
Features that assist in adhering to host cells and invading host tissues.
Development of these factors requires energy investment and typically occurs in response to selective pressures from the host.
Host Factors & Virulence: The association of virulence with host properties such as:
Immune fitness and balance of normal microbiota.
Mechanisms of damage caused by virulence factors:
Directly harm host cells.
Induce exaggerated immune responses.
Historical examples of virulence:
The Influenza pandemic of 1918 was particularly virulent in young adults while being less impactful on older patients.
SARS-CoV-2 infections are notably often asymptomatic in children, illustrating variability in virulence related to age.
Transmission & Virulence: The connection between virulence factors and pathogen transmission:
Contagious pathogens tend to have increased prevalence in populations:
Example: Pathogens spread via respiratory droplets.
Pathogens causing asymptomatic cases are prone to creating epidemics or pandemics:
Example: Many sexually transmitted infections (STIs).
Symptoms categorized as aggressive can limit pathogen spread:
Illness often limits social interaction (e.g., staying away from others when ill).
Basic Reproduction Number (R0): A crucial measure of a pathogen's transmissibility or contagiousness:
For instance, an R0 of 2.0 indicates that one infected individual is expected to infect an average of 2 other individuals in a fully susceptible population.
Measles has the highest known R0, approximately 15.
Toxins as Major Virulence Factors:
Toxins: Molecules resulting in various adverse effects on hosts, including tissue damage and suppressed immune responses.
Toxigenic organisms: Bacteria capable of producing toxins.
Toxemia: The presence of toxins in the bloodstream.
Classification of toxins:
Endotoxins:
Found in Gram-negative bacteria, characterized by an outer membrane rich in lipopolysaccharide (LPS).
LPS consists of:
A lipid portion (Lipid A) and sugars.
Lipid A is identified as endotoxin, toxic to hosts.
Trigger severe immune responses leading to symptoms such as:
Fever, chills, body aches, low blood pressure, leading potentially to septic shock and organ failure upon the death of the bacteria.
Exotoxins: Soluble proteins produced by both Gram-positive and Gram-negative bacteria;
Affect a broad spectrum of host cell types.
Typically heat-stable and named for their source organism or targeted cell types (e.g., neurotoxins, enterotoxins, hepatotoxins, nephrotoxins).
Over 200 distinct exotoxins have been identified and classified into three families based on action types:
Type I: Superantigens that cause excessive immune system stimulation, leading to harmful inflammation.
Type II: Cause membrane disruptions or cell lysis.
Type III: Enter host cells and exert intracellular effects.
10.3: 5 Steps to Infection
A successful pathogen must accomplish five key tasks to establish an infection:
Pathogen Entry:
Portal of entry: Any site a pathogen utilizes to enter a host, typically mucous membranes which are the most common, although not exclusively the main infection site.
Examples of portals of entry:
Skin, eyes, ears, respiratory tract (most common), gastrointestinal tract, urogenital tract, parenteral (injection), and transplacental.
Adhesion to Host Tissues:
Initial adhesion often relies on non-specific mechanisms before targeting specific surface molecules on host cells.
Tissue and species tropism arises from specificities in host cell surface markers.
Adhesion Factors: Includes various virulence factors enabling pathogen attachment to host cells:
Adhesins such as cell wall components, capsules, fimbriae, pili, and different plasma membrane-associated molecules.
Invasion and Nutrient Acquisition:
Pathogens inflict damage to host tissues while acquiring nutrients:
This damage may result in cytopathic effects.
Invasins: Factors that allow pathogens to penetrate host tissues, including extracellular enzymes that break down host tissues, form blood clots, or induce host to internalize pathogens.
Evasion of Host Immune Defenses:
Hiding from Host Defenses: Intracellular pathogens, including viruses, many protozoans, and certain bacteria, predominantly reside within host cells, thus protected from immune detection.
Latency: A pathogen’s ability to exist quietly within a host; often related to chronic or recurring diseases, provides protection from immune responses and may confer resistance to drug therapies.
Antigenic Manipulation:
Antigenic masking: Pathogens obscure antigenic features by coating themselves with host molecules.
Antigenic mimicry: They mimic host molecules (e.g., capsules resembling host carbohydrates).
Antigenic variation: Pathogens periodically change surface molecules to evade rapid immune reactions, facilitated by genomic mutations causing protein expression alterations.
Undermining Immune Response: Includes targeting immune cells, producing proteases that degrade host antibodies, disrupting immune protein transcription, and interfering with immune signaling pathways.
Transmission to New Hosts:
Symptoms generated may enhance pathogen transmission, e.g., itchiness, sneezing, coughing, diarrhea.
Portal of Exit: Refers to routes utilized by pathogens to exit hosts:
Include feces, urine, and bodily fluids: blood, secretions from wounds, vomit, saliva, mucus, or semen, often coinciding with the portal of entry.
10.4: Safety & Healthcare
Infection Control Practices: Essential in healthcare settings to protect both patients and healthcare workers.
Most healthcare facilities employ infection control teams to minimize infection risks.
Standard Precautions: Guidelines applying to all patients to limit bloodborne pathogen transmission, treating all patients as potential sources.
Handling protocols exist for managing all bodily fluids:
Hand washing before and after patient contact, changing gloves between different tasks or procedures, using barrier clothing, face shields, or masks.
Proper disposal of biosharps waste.
Disinfection practices for surfaces, linens, and garments.
Transmission Precautions: These are additional measures used when specific infections are suspected or confirmed.
Informational signage for healthcare providers and visitors to prevent direct contact, droplets, or airborne transmission.
Contact Precautions: Minimize transmission spread by fomites and healthcare worker contact:
Requires barrier gowns and gloves in the patient room and limited patient transport applications.
Examples include MRSA and C. difficile.
Droplet Precautions: Mandates wearing procedural masks while in the patient's vicinity and restricting transport of the patient:
During transport, the patient is required to wear a mask.
Examples include rubella, influenza, and pertussis.
Airborne Precautions: Patients may be required to be housed in specialized airborne infection isolation rooms (AIIR), which utilize negative pressure and may necessitate the use of N95 or better respirators:
Examples include tuberculosis, chickenpox, and measles.