Lecture 6: Host Microbe Relationship & Infection

Symbiosis

Living-together and interaction between 2 different species in such a way that at least one species benefits

Host vs Symbiont

The larger organism is the host

While the smaller one is the symbiont (always benefits)

Commensalism

Host neither benefits nor gets harmed

Mutualism

Host benefits

Parasitism

Host is harmed

Parasite

Organisms that lives on or in another organism (host), benefiting from it while causing some harm

Types of parasites

Microparasites and macroparasites

Normal flora (microbiota)

Microorganisms normally colonizing skin and mucus membrane of humans and animals

Predominant normal flora species

Bacteria, but fungi, viruses, and protozoan can be found

bacteria vs own cells in humans

10^14 bacteria

10^13 own cells

Our normal flora has at least the same amount to 10x as more bacteria than our own cells

Composition of normal flora

Differs from site to site (habitat) due to differences in key ecological factors (pH, anaerobiosis, nutrients, adhesion ligands, etc.)

Resident flora

Members of the normal flora that are regularly found at a particular habitat

Transient flora

Members of normal flora that are only occasionally found at a particular site and for short periods

(Ex: sneezing in your hand)

Skin normal flora

Gram (+):

• staphylococci (s. Aureus and s. Epidermis)

• Micrococcus

• Corynebactia

• Propionibacteria

Fungus:

• malassezia

Oral cavity normal flora (diverse!)

Gram (+):

• streptococci (most dominant)

• Rothia

• Actinomyces

Gram (-)

• Neisseria

• Haemopilus

• Fusobacterium

Fungus:

• candida

Intestine normal flora (varies from site to site in intestine)

Gram (+)

• entrococci

• Bifidobacteria

• Lactobacilli

• Clostridium

Gram (-)

• Bacilli (enterobacteria - E. Coli, Klebsilla, protus, etc.)

• Bacteroides

• Fusobacterium

Pharynx and larynx normal flora

Gram (+)

• oral streptococci

• Strep. Pyogenes (can cause tonsillitis)

• Strep. Pneumonia (if goes to lungs can cause harm to susceptible host)

Gram (-)

• anaerobes

• Haemophilus influenza (takes advantage of susceptible host)

Vagina normal flora

Gram (+)

• lactobacilli

• Streptococci

• Staphylococci

Fungus

• candida

Lower respiratory tract normal flora

Usually sterile

Commensal / mutualistic interactions with normal flora

This is usually the case

• synthesis of vitamins (ex: vitamin K by intestinal bacteria)

• Stimulation of development of certain tissues (lymphoid tissues)

• Colonization resistance (little to no place for pathogens)

Parasitic interactions with the normal flora

An opportunistic infection

• when host immunity is compromised

• When normal flora from one site goes to another part of the body

• When colonization resistance is disturbed (antibiotics)

Pathogen

Microorganisms (or virus) that can cause disease

Obligate pathogen (parasite)

One that causes disease as part of its life cycle

Ex: Neisseria gonorrhea, obligate intracellular bacteria, and viruses

Accidental pathogen (not a parasite)

One that lives independently of the host, in the environment or in other species, but will cause disease if accidentally introduced

Ex: clostridium tetanus or salmonella entriditis

Opportunistic pathogen (parasite)

One that causes disease only under unusual circumstances

Pathogen vs Parasites

All parasites are pathogens BUT not all pathogens are parasites

Parasite lives with us and causes disease

Pathogens are introduced and cause disease

Defining a pathogen

Henle-Koch’s postulates

1. The microorganism must be found in all diseased subjects but in non of the healthy subjects

2. The microorganism must be cultivated in pure form in vitro

3. Inoculation of the microorganism in a laboratory animal must produce a similar disease

4. The microorganism must be re-isolated from lesions of the experimental animals

*not always applicable

Colonization

Presence and growth of a microorganism on a host tissue surface WITHOUT causing damage

Infection

Multiplication of a pathogen in or on a body tissue, INDUCING some sort of damage

Infectious disease

A disease caused by a pathogen

Communicable diseases

An infectious disease that can pass from one individual to another

Non-communicable diseases

An infectious disease that is acquired from the environment or other species, by ingestion of a bacterial toxin or caused by normal flora

Pathogenesis

The mechanism by which infection and disease develop

Pathogenicity

The ability of a microorganism to cause disease

Virulence

The degree of disease a pathogen has the potential to cause

Virulence factors

The properties of a pathogen that allow it to cause disease (virulent vs. non-virulent strains)

Infectious dose

Minimum number of a pathogen required to ensure infection

Subclinical (unapparent) infection

No clinical symptoms (majority of infections)

Acute infection (fulminant if very severe)

Rapid onset- brief duration

Ex: measles

Chronic infection

Prolonged duration, virus is continually released from the cell and multiplying, always positive in a test result

Ex: HIV, Hep B

Latent infection

Signs and symptoms appear after a long while, and can stay below detection limits

Etc: herpes, shingles

Infections according to spread

Localized

Generalized/systemic

Permissive infection

Lytic cycle, lyses the cell and multiplies

Non permissive infection

Lysogenic- virus integrates within the cell

Mono-species infection

Infection caused by one pathogen

Mixed infection

Infections caused by more that one pathogen

Primary infection

Infection by a virulent pathogen in immunocompetent host

Secondary infection

Subsequent to a primary infection

Opportunistic infection

Caused by opportunistic pathogens

Vertical transmission in humans

Infection passed from parents to offspring

• prenatal through placenta

• Perinatal via infected birth canal

• Postnatal via milk, direct contact

• Germline via ovum or sperm (viral DNA)

Horizontal transmission in humans

• droplet (respiratory/saliva): large - fall within a meter

• Airborne (respiratory/saliva): small - remain suspended in the air (measles, tuberculosis, varicella)

Direct contact (horizontal transmission)

• Skin to skin (herpes simplex, S. Pyogenes and S. Aureus)

• Mucosal contact (syphillis, HIV, HBV)

• Fecal-oral route (shigella, Hep A)

Indirect contact (horizontal transmission)

• animate surface

• Needle stick injuries (HIV, HCV, HBV)

• Drug abuse (HIV, HCV, HBV)

Common vehicle (horizontal transmission)

• blood / blood products (HIV, HCV, HBV)

• IV fluids (gram negative rods)

• Food - food borne (bacteria), food poisoning (toxin) (campylobacter, salmonella, and staphylococcus)

Arthropod borne (horizontal transmission)

Malaria

Transmission from animals (zoonoses)

• direct contact

• Eating

• Bites and scratches

• Inhalation of fecal or urine particles

• Arthropod borne

Microbial factors that affect the outcome of infection

Virulence and inoculum size (amount of pathgogen)

Host factors that affect the outcome of infection

• immune status

• Vaccination status

• Sex

• Age

• Ethnicity

• Antibiotic usage

Incubation period

The period between the entry of the pathogen and appearance of clinical features

Prodormal period

A period during which non-specific symptoms and signs may appear

Invasive phase (full blown illness)

Typical signs and symptoms become apparent

Acme

Illness peak

Decline phase

Signs and symptoms fading

Convalescence period

A period during which damage is being repaired

First step of infection

Entry: via natural orifices, wounds or burns, parenternally, bites

Second step of infection

Attachment: adherence to host surface by specific adhesion-ligand interactions

Third step of infection

Multiplication: increase in number, formation of micro colonies, formation of biofilm

Fourth step of infection

Invasion/causing damage: directly or indirectly depending on the disease

Fifth step of infection

Spread: locally or systemically

Sixth step of infection

Exist: usually, but not always, a reverse of entry mechanism

Bacteria attachment virulence factors

• fimbrae (common Pili in gram neg.)

• Fibrillation (gram pos.)

• Outer membrane proteins

• Surface proteins

• Capsule/slime

• Lipoteichoic acid

• Enzymes that expose surface receptors on host surfaces

Virus attachment virulence factors

• adhesion receptors (concentration on the surface)

• Entry receptors (entering the cell)

Specific bacteria attachment

Adhesin on pili bind to receptor ligand to anchor bacteria to allow it to attach to host membrane via Attachemnt protein

Viral Attachemnt

Virus attaches to adhesion receptors and diffuses to bind to entry receptor to enter host cell

Biofilm

An intelligent community of bacteria attached to a solid surface and encased in a polysaccharide matrix

Biofilm properties

• integrated metabolism (in multi species biofilms)

• Altered phenotype

• Enhanced resistance to immune response

• Increased resistance to antimicrobials

Biofilm examples

• pseudomonas aeruginosa infections of the respiratory tract in cystic fibrosis patients

• Staph. Aureus infections in central venous catheters

• Chronic periodontitis due to dental plaque

Exotoxins

Soluble proteins, often enzymes, secreted by viable bacteria, which cause DIRECT damage to the hose

Enterotoxin exotoxin

Act on the gastrointestinal tract

Neurotoxin exotoxin

Act on the nerves

Phospholipases

Breaks phospholipid bilayers

Protestase

Break down protein

Collagenases

Break down collagen

ADP-ribosylating

Changes the function of the cell

Proteases and collagenases

Work extracellularly on connective tissue and spread

Cytotoxic

Kills cells

Cytolytic

Cell gets lysed by damaging or forming pores in cell membranes

Cytotonic

Deregulates cell functions

Direct damage without exotoxins

• Metabolic end products

• Invasion of and multiplication within the host cells by (lyses the cell):

  • Obligate intracellular bacteria (while invading it damages the cell)

  • Viruses

Indirect damage

Results from an overt immune response

Simply: the immune response inflicts the damage because of the bacteria infection

Endotoxins

The LPS component of the outer membrane of gram neg bacteria

Released only when the bacteria dies

Superantigen

Staphylococcal toxic shock syndrome toxin (an exotoxin)

Other indirect virulence factors

• peptidogylcan

• Teichoic acids

• Viral infection (cell mediated cytotoxicity)

Septic shock

LPS induces a storm of cytokines

Depending on where response occurs can have local, systemic effects or even cause septic shock

Direct dental damage

Dental caries: bacteria produces an acid to cause caries

Indirect dental damage

Periodontitis: bacteria cause immune system to respond and damage oral health

Evasion of physical and mechanical barriers

• adherence

• Interfere with ciliary activity bu colliotoxic/ciliostatic molecules

• Transversing host cell membrane (Endocytosis)

• Active cell penetration

Evasion of phagocytosis

• inhibition of Chemotaxis (doesn’t allow WB cells to come)

• Killing by leucocidins and cytolytic toxins (kill WB cells)

• Inhibition of phagocytosis via capsule (capsule is too big to be engulfed)

• Inhibition of lysosomal fusion

• Resisting killing inside phagocytes (remain active within neutrophils and macrophages)

Evasion of complement

• camouflage (antigenic mimicry): covering surface with material to mimic host material

• LPS: activates complement far away from the microbial surface so no damage done to cell

• Inactivation of complement components

Evasion of antibody-mediated immunty

• antibody destruction (IgA proteases ): degrades antibodies, inhibits plasma/b-lymphocytes, kills antibodies

• Inhibition of production

• Camouflage

• LPS