Microbial Ecology Relationships

Host-Pathogen Interaction

• Host-pathogen interactions, the environment, and other microbes define the "disease triad".

Ecological Relationships

• Mutualism (+/+) is a mutually beneficial relationship between two species.
• Commensalism (+/0) is a relationship between two species where one benefits and the other is neither positively nor negatively affected.
• Parasitism (+/-) is a relationship where one species (the parasite) benefits from the other (the host), typically with detriment to the host.
• A saprophyte is a microbe that lives off dead or decaying plant matter, such as fungi on a dead tree trunk.

Basic Ecological Definitions

• Flora or microbiota refers to the microorganisms present in a specific location.
• Indigenous (resident) microbiota are the microbial flora typically occupying a particular niche, given the diversity of environmental conditions.
• Transient flora are microbial flora only temporarily taking up a given niche

Natural Microbial Habitats

• Microbes live in soil, water, air, and in/on animals and animal products.

Microbial Flora of the Normal Human Body

• Skin
• Respiratory Tract includes the nose, nasopharynx, mouth, and oropharynx.
• Eye (conjunctivae) and outer ear
• Intestinal Tract includes the stomach, small intestine, and large intestine.
• Genitourinary Tract includes the external genitalia, anterior urethra, and vagina.

Normally Sterile Sites in the Human Body

• These sites' colonization typically involves a defect or breach that creates a portal of entry
• Brain and central nervous system
• Blood, tissues, and organ systems
• Sinuses, inner and middle ear
• Lower respiratory tract: larynx, trachea, bronchioles, lungs, and alveoli
• Kidneys, ureters, and urinary bladder
• Uterus, endometrium (inner mucous membrane), and fallopian tubes

Factors Controlling Growth of Microorganisms

• Nutrient availability refers to the accessibility of necessary resources for life, such as conversion to energy and structural building blocks.
• Fastidious organisms have complex nutritional needs, making isolation and culture challenging.
• Competition arises when two or more organisms/species simultaneously demand a common resource in limited supply, leading to a struggle for survival.
• The host immune system involves cells and tissues recognizing and attacking foreign substances.

Acquiring Infectious Agents

• Portals of entry/exit are how agents enter and leave the host.
• Routes of entry include ingestion, inhalation, and direct penetration (trauma, surgical procedure, needlestick, or arthropod bite).
• Colonization is the successful occupation of a new habitat by a species not normally found there.
• Adherence (attachment) is a close association between bacterial and host cells, often via receptors on target sites.
• Adhesin is a structure on a cell surface or extracellularly that facilitates adherence to another surface/cell, often via specific receptors, but can be nonspecific.
• Invasion is the entry and spread throughout the host's cells/tissues; receptor recognition enhances pathogenic advantage.
• Invasins are molecules facilitating invasion by pathogenic microorganisms..
• Multiplication is microbe's ability to reproduce during an infection, influenced by disease, immunity, antibiotics & nutrient availability.

Transmission of Disease

• Entrance, colonization, and penetration depend on age, nutrition, immune status, host health & bacterial virulence
• A vector is a carrier, especially an animal such as an arthropod, that transfers an infectious agent from one host to another.
• A carrier is a symptomless individual hosting a pathogenic organism with the potential to transmit it.
• Nosocomial infections are acquired in a hospital setting, not present in the host upon admission.

Nosocomial Infections in Acute Care Institutions

• Urinary tract infections are commonly caused by Escherichia coli, Enterococcus, Proteus, Klebsiella, Pseudomonas aeruginosa.
• Surgical wound infections commonly involve Staphylococcus aureus, Staphylococcus epidermidis, E. coli.
• Pulmonary infections commonly involve Klebsiella, Pseudomonas, E. coli, and S. aureus.
• Primary bacteremia infections commonly involve S. aureus, S. epidermidis, and Gram-negative rods.
• Other infections commonly involve S. aureus and E. coli.

Epidemiology

• An epidemic is a disease occurring suddenly in numbers clearly exceeding normal expectancy.
• An endemic is a disease present or usually prevalent in a population/geographic area at all times.
• A pandemic is a widespread epidemic, distributed globally.

Pathogenicity vs. Virulence

• Pathogenicity is the quality of producing disease or causing pathologic changes.
• Virulence is a degree of pathogenicity; ability to produce disease, gauged by severity and dosage required for pathogenicity.
• A true pathogen can cause disease in most cases and is therefore an infecting agent.
• An opportunistic pathogen is a typically harmless microorganism that becomes pathogenic under favorable conditions, causing opportunistic infections.

Bacterial Virulence Mechanisms

• Adherence (Colonization)
• Invasion
• Degradative enzymes
• Exotoxins
• Endotoxin
• Induction of excess inflammation
• Evasion of phagocytic & immune clearance
• Superantigen
• Resistance to antibiotics

Microbial Pathogenicity: Virulence Factors

• Colonization Factors: specific recognition of receptor sites on target cells enhances pathogenic advantage
• Capsule: nonspecific attachment
• Surface Receptors/Target Sites: receptors on both bacteria (adhesins) and host (target)
• Fimbriae (formerly known as pili) of Enterobacteriaceae

Virulence Factors

• Invasive Factors (invasins): enable a microorganism to enter/spread throughout host tissues
• Degradative Enzymes: proteins capable of catalyzing reactions; both bacterial and host enzymes play roles in disease

Virulence Factors Related to Toxins

• Toxigenicity: the ability of a microbe to cause disease via toxins, determining virulence
• Endotoxin: complex bacterial toxin of protein, lipid & polysaccharide (LPS), released upon cell lysis.
• Exotoxins: Potent toxins formed and secreted by specific bacteria species.

Basic Effects of Endotoxin

• Fever: elevation of body temperature above normal
• Leukopenia/Leukocytosis: abnormal leukocyte count (<5000/mm³) or high (>12,000mm³) due to hemorrhage, infection, inflammation, or fever
• Metabolic Effects: pathogenic organisms disrupt metabolic processes (hypotension, hypoglycemia, etc.)
• Release of Lymphocyte Factors: agranular leukocyte reacts in immunological responses, including antibody production
• Septic Shock: overwhelming infection, vascular failure, complement activation, and histamine/prostaglandin release
• Disseminated Intravascular Coagulation (DIC): blood coagulation element reduction due to vessel clotting
• Organ Necrosis: host cell death causing organ failure

Exotoxins

• Two-Component (Bipartite) A-B Toxins with Intracellular Targets:
  • One part (B subunit) is a binding domain to the host cell
  • The other part (A subunit) is an active domain that enzymatically disrupts cell function
• Bacterial Cytolysins (Cytotoxins) with Cell Membrane Targets
  • Hemolysis
  • Tissue necrosis
  • Can be lethal intravenously

Examples of Bipartite A-B Toxins with Intracellular Targets

• Diphtheria toxin - inhibits cell protein synthesis, causing cell death and pseudomembrane formation.
• Cholera toxin - A-subunit catalyzes ADP-ribosylation, leading to life-threatening diarrhea.
• Tetanus neurotoxin - binds to neuroreceptor gangliosides, causing spasms and trismus.
• Botulinum neurotoxin - inhibits acetylcholine release at myoneural junctions, causing fatal paralysis.

Microbial Pathogenicity: Resistance to Host Defenses

• Encapsulation and antigenic mimicry, masking, or shift
• Capsule, Glycocalyx, or Slime Layer:
  • Polysaccharide capsules of Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, etc.
• Evasion or incapacitation of phagocytosis and/or immune clearance
• Phagocytosis Inhibitors: resisting engulfment, ingestion, and lysis by phagocytes/phagolysosomes
• Resistance to humoral and cellular factors

Microbial Pathogenicity: Damage to Host

• Direct Damage: tissue damage from toxins/enzymes.
• Indirect Damage: tissue reactions from vigorous immune response, such as Hypersensitivity Reactions (Types I - IV).

Host Defense Mechanisms

• External (Primary) include physical barriers like skin and endothelial linings of the respiratory, gastrointestinal, and genitourinary traits.
• Mechanical/Physical Factors: sweat, pH, indigenous flora, peristalsis, hair, cilia, urinary flushing, mucus, tears, lysozyme in saliva, spermine in semen, and IgA antibody
• Internal (Secondary)
• Cellular defense mechanisms include local macrophages and blood-borne phagocytic cells.
• Mononuclear phagocytes (monocytes/macrophages) and polymorphonuclear leukocytes (PMNs) target bacterial infections.
• Cellular Immune Response: immune response at the cellular level, includes processes like inflammation and phagocytosis.
• Inflammatory Response: protective reaction by tissues affected by disease or injury; characterized by redness, heat, swelling, pain, and potentially impaired function.
• Phagocytosis: phagocytes ingest extracellular particles that are opsonized with antibodies are more rapidly and effectively ingested
• T-Lymphocytes and Cytokines
• Humoral Immune Response: sum total of the immune response circulating in th; includes antibody and complement systems
• Complement Protective System: serum protein that combines with antibodies to defend against cellular antigens.
• B-Lymphocytes and Antibody Production: introduction of an antigen stimulates production of specific antibodies.