Host-Microbe Interaction

Host-Microbe Interaction

• Humans are colonized by microbes at birth and continuously throughout their lifetime.
• A fetus is sterile until birth, with the first exposure to microbes occurring during passage through the birth canal.
• The human body constantly comes into contact with many microorganisms daily by breathing, ingesting food/drink, and skin contact.
• Relatively few microbes encountered are pathogenic.
• Normal microbiota (flora) routinely reside on the body's surfaces.
• Resident microbiota are permanent colonies that do not cause disease.
• Transient microbiota inhabit the body temporarily.
• Normal microbiota prevents pathogens from causing infection through microbial antagonism.
• The composition of normal microbiota is dynamic and changes due to physiological variations, genetics, and host activities.
• Intestinal microbes of obese and lean individuals differ.
• The Human Microbiota Project aims to better understand the effects of microbiota.
• Host/Microbe relationship is a delicate balance.
• Infection or disease occurs when the balance favors the microbe.
• Microbial pathogenicity mechanisms are key to understanding how pathogens overcome host defenses.
• Some microbes only cause disease when there is an opportunity
• This may due to weakened defenses (immunocompromised).
• It may also due to antibiotic treatment suppressing or killing other microorganisms, enabling over-colonization.
• Some antibiotics inhibit Lactobacillus in the vagina, which normally suppresses Candida albicans, leading to yeast infections.
• Oral antibiotics can inhibit intestinal microbiota, causing an overgrowth of C. diff.
• Disease can result from organisms in unusual locations. Growing organisms in a relatively germ-free environment can also have negative effects.

Pathogenicity Overview

• For a pathogen to cause disease, it must:

• Gain access to the host

• Adhere to host tissues

• Penetrate or evade host defenses

• Damage the host directly or through waste accumulation

• Infectious diseases yield objective signs and subjective symptoms from the damage

• Virulence is the degree of pathogenicity.

• Virulence factors are traits that enable a pathogen to cause disease.

• The course of infectious diseases includes the incubation period, illness, and convalescence (recovery).

Mechanisms of Pathogenicity

• When the host-microbe balance favors the microbe, infection or disease can occur.
• The cycle includes: portal of entry -> number of invading microbes + adherence -> penetration or evasion of host defenses -> damage to host cells -> portal of exit

Portals of Entry

• Microbes enter through portals of entry, and exit through portals of exit.
• Common portals of entry include:
• Mucous membranes (respiratory, gastrointestinal, genitourinary tracts, conjunctiva)
• Skin
• Parenteral route
• Respiratory Tract: Microbes are inhaled into the mouth or nose via moisture droplets or dust particles. This is considered the easiest and most common route of entry.
• GI Tract: Microbes enter through contaminated food, water, fingers, and hands; most are destroyed by enzymes or bile.
• Genitourinary System: STDs fall into this category
• Conjunctiva: Microbes gain entrance in the mucus membranes covering the eyeball and lining the eye.
• Skin: An effective barrier when unbroken, some microbes enter through openings such as hair follicles and sweat glands.
• Parenteral Route: Microbes are deposited below the skin or mucous membranes via punctures, injections, bites, scratches, surgery, or skin splitting due to swelling or dryness.
• Pathogens must enter the body through a portal that allows them to cause disease.

Preferred Portal of Entry

• Salmonella typhi causes typhoid fever only when it enters the GI tract but not when on the skin.
• Some can cause disease from multiple portals eg. Bacillus anthracis.

Number of Invading Microbes

• The likelihood of disease increases with more invading pathogens.
• ID50 (Infectious Dose) is the number of microbes needed to infect 50% of a population.
• ID50 varies for different pathogens and portals of entry for the same pathogen.
  • Skin: 10-50 endospores
  • Inhalation: 10,000-20,000 endospores
  • Ingestion: 250,000-1,000,000 endospores
• LD50 (Lethal Dose) is the amount of toxin needed to kill 50% of a population within a specific time frame.
• Adherence is microbe attachment to a host at the portal of entry, is needed for virulence, and can be prevented by blocking adhesion.
• Adherence involves specific molecule binding between host and pathogen.

Virulence and Host Defenses

• Virulence is indicated by a microbe's ability to establish itself in the host and cause damage.
• Pathogens encounter resistance from host defenses (e.g., phagocytes).
• Antiphagocytic factors are virulence factors that help pathogens avoid phagocytes.
• Some microbes outright kill phagocytes by producing leukocidins toxic to WBCs (e.g., Streptococcus and Staphylococcus)
• Capsules can prevent phagocytosis (e.g., Streptococcus pneumoniae)
• Slime layers make it difficult for phagocytes to engulf microbes.
• Some survive inside phagocytes due to their cell wall composition (e.g., Mycobacterium)

Damage to Host Cells

• Pathogens that survive host defenses can damage host cells. Damage can be done by:
• Secreting proteins (enzymes/toxins) directly.
• Exoenzymes:
• Coagulase: clots fibrin in blood, creating a protective barrier against host defenses and preventing phagocytosis by WBCs (e.g., Staphylococcus)
  • Kinases: dissolve clots to allow escape from isolated wounds (e.g., Streptokinase (S. pyogenes) and Staphylokinase (S. aureus))
• Hyaluronidase: breaks down hyaluronic acid ("glue" in connective tissue), allowing deeper invasion (e.g., Staphylococcus, Streptococcus, Clostridium)
• Toxins: are poisonous chemicals:
• Toxemias: toxins spread by blood from the site of infection (e.g., tetanus)
• Intoxications: result from the ingestion of toxins (e.g., botulism)
• Toxins are named based on their specific target:
• Neurotoxins: target the nervous system. (Clostridium toxins interrupt key cell pathways and prevent nerve-muscle stimuli transmission)
• Enterotoxins: target the intestines
• Hemotoxins: target RBCs (hemolysins are discussed as Streptococcus pyogenes and Staphylococcus aureus)
• Nephrotoxins: target the kidneys
• **Exotoxins are secreted by living bacteria into the infected tissue.
• Endotoxin is shed from the outer membrane of gram-negative bacteria, and causes a systemic response with fever, inflammation etc eg. Neisseria, E. coli, Shigella.

Exotoxins vs. Endotoxins

• Exotoxins:
  • Source: Gram-positive and gram-negative bacteria
  • Relation to microbe: By-products of growing cell
  • Chemistry: Protein
  • Fever: No
  • LD50: Small
• Endotoxins:
  • Source: Gram-negative bacteria
  • Relation to microbe: Outer membrane
  • Chemistry: Lipid A
  • Fever: Yes
  • LD50: Relatively large
• Additional Pathogenic Effects
  • Causing an overreaction of the body's defenses that results in damage
  • Host excessive or inappropriate response to a microorganism.
  • Pathogenicity is not just influenced by the characteristics of the microorganisms.
  • Alteration of the host cell genome or transcription processes.
  • Microbes shut down or activate DNA regions via epigenetic processes.
  • Changes the way host cells function and may persist, causing continuing symptoms.

Portals of Exit

• Means of exit by pathogens, often released during secretion, excretion, or discharge.
• High pathogen numbers increase the likelihood of reaching a new host.
• V. cholerae induces watery diarrhea (up to 20L a day).