Chapter 11: Interactions Between Microbes and Humans

Introduction

This chapter explores the complex relationships between humans and the microbial world, focusing on the human microbiome, the process of infection, disease development, and the mechanisms by which microbes interact with and affect their hosts. Understanding these interactions is fundamental to the study of pathogenesis, epidemiology, and the control of infectious diseases.

The Human Microbiome

Definition and Importance

• Human microbiome: The sum total of all microbes found on and in a normal human.

• These microbes are critically important to the health and functioning of their host organism.

Colonization, Infection, and Disease

• Colonization: The long-term presence of resident microbiota on the host, typically without causing disease.

• Infection: Occurs when microbes bypass host defenses, enter tissues, and multiply.

• Disease: A deviation from health resulting from the cumulative effects of infection that damage or disrupt tissues and organs.

• Infectious disease: A pathologic state caused directly by microorganisms or their products.

The Human Microbiome Project (HMP)

• Launched in 2007 as a worldwide research effort.

• Aims to characterize microbes living on healthy human bodies and determine how the microbiome differs in various diseases.

• Utilizes genome sequencing and big data tools.

Key Findings from HMP

• Human cells encode about 21,000 proteins, while the microbiota encode millions.

• Microbes are found in locations previously thought to be sterile (e.g., lungs, bladder, breast milk, amniotic fluid, and even the brain and bloodstream).

• All healthy people harbor potentially dangerous pathogens in low numbers.

• The composition of intestinal biota can influence overall health.

Sites with Microbiota

• Previously known sites: Skin, mucous membranes, upper respiratory tract, gastrointestinal tract (including mouth), outer urethra, external genitalia, vagina, external ear canal, external eye.

• Newly recognized sites: Lungs, bladder, breast and breast milk, amniotic fluid, fetus.

• Sites with detected microbial DNA: Brain, bloodstream.

Acquisition and Role of Microbiota

• The human body provides diverse environmental niches for microbes.

• Microbial antagonism: Resident biota prevent colonization by incoming microbes through competition for attachment sites and by creating hostile environments.

• Normal biota are generally beneficial or commensal in healthy individuals.

Factors Weakening Host Defenses

• Old age, infancy, prematurity

• Genetic or acquired immune defects (e.g., AIDS)

• Surgery, organ transplants

• Underlying diseases (cancer, diabetes, liver malfunction)

• Chemotherapy, immunosuppressive drugs

• Physical/mental stress, pregnancy, other infections

Colonization of the Fetus and Newborn

• The placenta harbors a small but significant array of bacteria.

• During birth, Lactobacillus and other species colonize the newborn, aiding digestion and protecting against disorders.

• Human milk contains about 600 species of bacteria and unique sugars that nourish healthy gut bacteria.

Pathogenicity and Virulence

Definitions

• Pathogen: A microbe whose relationship with its host is parasitic, resulting in infection and disease.

• Pathogenicity: The organism's potential to cause disease.

• True pathogens: Cause disease in healthy individuals.

• Opportunistic pathogens: Cause disease when host defenses are compromised or when introduced to unusual body sites.

• Virulence: The relative severity of disease caused by a microbe; determined by its ability to establish in the host and cause damage.

• Virulence factor: Any characteristic or structure of the microbe that contributes to its ability to establish itself and cause damage.

Polymicrobial Infections

• Most infections involve multiple microbial species (polymicrobial).

• Example: Influenza infection can lead to pneumonia; skin infections may involve Staphylococcus, Streptococcus, and Moraxella.

Steps in Microbial Pathogenesis

Step 1: Becoming Established – Portals of Entry

• Portal of entry: The route a microbe takes to enter host tissues.

• Exogenous: Originates outside the body.

• Endogenous: Originates from within the host.

• Pathogens are often adapted to specific portals; entry via the wrong portal may not result in infection.

• Some pathogens can use multiple portals (e.g., Mycobacterium tuberculosis).

Table: Portals of Entry and Organisms Typically Involved

Step 2: Attaching to Host Cells (Adhesion)

• Microbes use specific molecules to bind to host tissues.

• Attachment is essential for infection, as the body has mechanisms to flush out unattached microbes.

• Mechanisms: Fimbriae (pili), surface proteins, adhesive slimes/capsules (bacteria, fungi, protozoa); specialized receptors (viruses); suckers/hooks/barbs (parasitic worms).

Step 3: Surviving Host Defenses

• Phagocytes: Host cells that engulf and destroy pathogens.

• Antiphagocytic factors: Leukocidins (kill phagocytes), extracellular layers (slime/capsule), survival inside phagocytes.

Step 4: Causing Disease

• Microbes cause damage by:

  • Direct action of enzymes or toxins (endotoxins/exotoxins)

  • Indirectly, by inducing excessive/inappropriate host responses

  • Epigenetic changes to host cells

Extracellular Enzymes (Exoenzymes)

• Break down host tissues and promote spread of infection.

• Examples: Mucinase (digests mucous membranes), hyaluronidase (digests cell cement), coagulase (clots blood), kinase (dissolves clots).

Bacterial Toxins

• Toxin: A chemical product of microbes that is poisonous to other organisms.

• Types:

  • Neurotoxins (nervous system)

  • Enterotoxins (intestine)

  • Hemotoxins (red blood cells)

  • Nephrotoxins (kidneys)

Exotoxins vs. Endotoxins

• Exotoxins: Secreted proteins, highly toxic in small amounts, specific targets, can be converted to toxoids for vaccines (e.g., hemolysins).

• Endotoxins: Lipopolysaccharide (LPS) from gram-negative bacteria, released on cell lysis, cause systemic effects (fever, inflammation, shock).

Types of Infections

Definitions and Examples

Warning Signals of Disease

• Sign: Objective evidence observed by others (e.g., fever, rash).

• Symptom: Subjective evidence sensed by the patient (e.g., pain, fatigue).

• Syndrome: A disease identified by a specific set of signs and symptoms.

Signs and Symptoms of Inflammation

• Symptoms: Fever, pain, soreness, swelling.

• Signs: Edema (fluid accumulation), granulomas/abscesses (walled-off cells), lymphadenitis (swollen lymph nodes).