Microbial symbiosis - living together of two dissimilar organisms; may be divided into different kinds of relationships

a. mutualism - beneficial to both.

b. commensalism - beneficial to one; not harmful to other.

c. parasitism - beneficial to one; harmful to other.

Majority of the normal flora - commensal or mutualistic relationship with the host. Example: 1011 bacteria/g fecal material - most harmless.

This can change if:

Colonization: growth of microbe on body surfaces; no recognizable reaction in the host.

Infection: Interaction between a host and a multiplying microbe that usually involves tissue (or cell) penetration and results in a host response to eliminate the microbe or to protect the host against further invasion or reinfection.

Infectious disease: infection that results in bodily dysfunction or a lesion - damage to the host. Unsuccessful relationship between parasite and host.

Note: infection does not equal disease. Isolation of a pathogen does not necessarily mean disease.

Endogenous or opportunistic infections are much more common now due to advanced medical technologies: radiation, treatment with cytotoxic drugs, treatment with corticosteroid hormones, malnutrition, shock, antimicrobial therapy, foreign bodies (catheters or prosthetic devices), and AIDS.

1. availability or unavailability of oxygen;

2. the availability of appropriate receptor sites for attachment;

3. the pH of the host site (stomach, vagina);

4. the availability of nutrients;

5. the influence exerted by other microorganisms at the site;

6. the immunological response of the host to the presence of the microbe.

Normal flora = indigenous flora = autochthonous flora = commensals

The skin, the oral cavity, the GI tract, and the female genital tract: resident normal flora

Esophagus, urinary tract, and stomach - few microbes.

Blood, spinal fluid, urine, and endothelial tissues - normally sterile.

The indigenous microflora will remain with the host for life, with only minor changes resulting from disease, dietary alterations, antibiotics, or hormonal changes.

SKIN - tough, thick outer layer - a natural barrier to invading microbes. Fatty acids secreted by the glands of the skin - inhibitory to microbial growth.

Resident microbes are not pathogenic unless the bacteria enter the host when the skin becomes abraded, IV catheters, or through the bite of animals or insects.

Below the larynx is normally sterile because of efficient cleansing action of mucociliary blanket that lines the bronchi.

b. nose - staphylococci, diphthroids, streptococci

c. GI tract - few bacteria survive in the stomach because of acidity. Those that survive the stomach enter the intestinal tract and encounter acids, bile salts, and enzymes.

Small intestine - some Gram-positives

d. vagina - differs before and after menarche

1. colonization resistance = bacterial antagonism = bacterial interference.

This is a bacterium-bacterium interaction whereby there is

a. competition for nutrients

b. competition for mucosal attachment sites

e.g Clostridium difficile - enterocolitis

Pseudomonas aeruginosa - invasive bacteremic infection.

2. Immunity - indigenous flora stimulates the immune system

1. Bacterial synergism - allows an organism to become pathogenic when ordinarily it is not.

Examples: Bacteroides melaninogenicus infects experimental animals when mixed with a diphthroid producing vitamin K (essential for growth of B. mel).

GC in the urethra may be protected against penicillin by penicillinase-producing staphylococci.

2. Opportunistic pathogens. If host immunity is impaired, normal flora bacteria (endogenous microbes) may cause disease.

e.g., alpha-hemolytic strep in the oral cavity may seed the bloodstream after dental extraction or even while brushing teeth. If heart valves are damaged, these bacteria can colonize the valves and cause subacute bacterial endocarditis.

Bacteroides spp. in the gut - ruptured appendix or knife wound

Contrast with exogenous organisms that may infect:

nosocomial infections - hospital-acquired infections (5% of admissions)

iatrogenic infections - physician- (or dentist-) induced

endemic - presence of infectious disease at the usual level in a population

epidemic - incidence of disease exceeding usual level

pandemic - whole world involved or a large portion of the world - e.g., influenzae pandemics, cholera pandemics

Of the thousands of microbial species, ≤ 300 can cause disease in humans.

Infectivity - ability of a microorganism to cause infection

Pathogenicity - ability of a microorganism to cause infectious disease, i.e., pathologic or pathophysiologic changes

Virulence - the degree of pathogenicity of a microorganism as indicated by

a. case fatality rates for an infectious disease

b. ability to invade and damage tissues of the host.

Organisms of moderate virulence have the best interaction with this host. If an organism is dependent on man for survival (has no reservoir in the natural environment, e.g. the gonococcus), it depends on man for its spread (e.g. ebola virus, smallpox virus). A highly virulent organism will eliminate the host and eliminate its own spread. The successful parasite is one that obtains enough nutrients to multiply without causing major damage to its host (e.g. pneumococcus, staphylococci, Treponema pallidum (syphilis).

Highly virulent bacteria generally have other stable reservoirs, either in other animals or in the soil. The plague bacillus (Yersinia pestis) colonizes rats without killing them, and anthrax spores survive for many years in the soil. Hantavirus asymptomatically resides in field mice.

Different strains of the same species vary in virulence. For example, a strain of Streptococcus pneumoniae that does not elaborate a capsule is unable to cause the type of disease associated with a capsule-producing strain. E. coli virulence - dependent on many plasmid-associated factors: toxins, adherence pili

Virulence factors - those components of an organisms that promote its capacity to cause disease but do not affect its viability, e.g. toxins and surface antigens that promote cellular adhesion or decrease interaction with phagocytes.

Factors influence bacterial virulence: growth rate, nutritional requirements, efficiency of iron uptake, temperature sensitivity, resistance to attack by oxidants or enzymes.

Virulence can be modified by serial passage in the laboratory or in an unnatural host. This reduction of virulence is called attenuation.

Some infections may lie dormant for years: TB. The microorganisms may emerge later if the individual becomes immunosuppressed or sometimes there is no apparent cause.

Some people asymptomatically carry pathogenic bacteria with no overt symptoms: AIDS, Salmonella typhi (Typhoid Mary was a cook who carried S. typhi; she spread typhoid to more than 50 people). Group A strep, Haemophilus influenzae type b.

Once a bacterium enters its host, it may take up residence within various cells of the body (intracellular parasite) or it may remain attached to the surface of host tissue (extracellular parasite).

Extracellular bacteria produce potent toxins or other proteins that enable them to colonize and damage tissue. These products induce an inflammatory response which helps the host recover from the disease. These are usually acute diseases.

Few microbes are able to survive intracellularly. These organisms are not directly exposed to various immune forces such as antibodies, immune cells, and other immune factors found in the bloodstream (or to many antibiotics that do not penetrate cells).

Some pathogens reside within phagocytic vacuoles (phagosomes) of professional phagocytes (e.g., macrophages): Chlamydia, Salmonella, Mycobacterium tuberculosis, Legionella, Coxiella, Yersinia, Brucella.

Pathogens that escape phagosomes (to cytoplasm): Rickettsiae, Shigella, Listeria.

1. Colonization of surfaces mediated by adhesins.

Selective localization of pathogens (organ tropisms)

Most adherence does not lead to invasion unless mechanical or chemical injury allows the bacteria to penetrate the skin or intestinal epithelium.

Some bacteria invade in the absence of mechanical injury.

From there, they can invade the underlying tissues.

Some invasive bacteria have the ability to survive within phagocytes.

Broad spectrum of invasiveness

3. Toxins - not found associated with microorganisms other than bacteria.

a. exotoxins

• most are heat labile proteins

• secreted by the bacterial cell into the surrounding environment without disruption of the bacterial cell

• most are produced by GP bacteria - tetanus, botulinum, diphtheria toxin, staphylococcal toxins, streptococcal toxins

• some GN’s also secrete exotoxins - cholera, pertussis toxin, E. coli

• vary widely in potency - some highly lethal, others cause morbidity but not mortality.

subunit B is nontoxic; binds to specific cell surface receptors; facilitates the entry of the second subunit (A)

subunit A is the toxic component

b. endotoxin -

a. Bacterial capsules

b. Cell wall components (M protein of Group A strep)

a. substances toxic to phagocytic cells, e.g. S. aureus leucocidin

b. Spreading factors

hyaluronidase (Strep. pyogenes)

collagenase (Clostridium perfringens, gas gangrene)

fibrinolysin (Group A strep)

proteases (many microbes)

lipases (many microbes