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Microbial Pathogenesis

Medical Microbiology

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Definitions

Microbial pathogenesis—process of causing disease

Colonization—presence of microbes at site of body– Does not imply tissue damage or disease

symptoms– Does imply invasion of site and multiplication

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Characteristics of Parasitism

Encounter: agent meets host Entry: agent enters host Spread: agent spreads Multiplication: agent multiplies Damage: agent, host response, or both

cause damage Outcome: agent or host wins, or coexist

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Encounter

In utero– Do not normally come in contact with organisms

Protection of fetal membranes Do not normally come in contact with organisms from

mother– Normally only present sporadically– Exceptions: sexual diseases, virus causes, rubella

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Encounter

At moment of birth– Come in contact with organisms present in

vaginal canal and on skin Previously, antibodies passed from mother to fetus Defenses are good for a period of time, then they wane

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Encounter

Challenge between man and microbe wages many times during lifetime– Most disappear rapidly– Some become part of normal flora– Only a few cause disease

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Later Encounters

Exogenous: encountered in environment Endogenous: encountered in or on body

– Organisms present on skin can cause disease when they go into deeper tissues

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Later Encounters

Example:– Staphylococcus aureus enters cut and forms boil– In this case, encounter took place long before

disease (at time skin was colonized)

Encounter is not always sharply demarcated

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Normal Flora

What constitutes normal flora?– Some people possess Streptococcus pyogenes in

their throat for long periods, but rarely contract disease

Opportunistic pathogen existence (carrier state)

– 95% of people never have this bacterium, and when they do, they get sick

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Normal Flora Defined

Constitutes normal flora if definition is “any organism present that is not causing disease”

Not normal flora if used to mean organisms present in majority of population

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Host-Parasite Interaction

Exposure to virulent agents does not always lead to disease– Typhus and Black Plague epidemics: only half

of population became sick, even though most likely exposed

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Host-Parasite Interaction

Response of particular microbe to particular host– Depends on factors unique to each interaction– Within a single individual– Changes with:

Age Nutritional state Other factors

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Entry

Much of inside of body is connected to the outside; for example:– Lumen of intestine– Alveoli of lung– Tubules of kidney

Almost all organs within thorax and abdomen are topologically connected to the outside

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Entry

Mechanisms to keep out invaders– Sphincters and valves– With exception of digestive and genitourinary

systems, these sites are normally sterile– Organism that resides on lumen side of intestine

or lung alveoli has not penetrated body

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Entry Defined

Ingress of microbes into body cavities contiguous with outside

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Digestive System

Enter through eating– Numbers of organisms are reduced one million or

more in stomach Bacillary dysentery can result from only a few hundred

organisms

– Not many survive in intestine because of digestive enzymes and strong force of peristalsis

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Digestive System

More survive in ileum, but need mechanisms to prevent expulsion– Surface components serve as adhesins to allow

adherence to epithelial cells Pili and surface polysaccharides

– Diseases such as cholera and “traveler’s diarrhea” are caused without penetrating epithelium

Toxins that affect epithelial cells

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Respiratory System

Enter through being inhaled– Air containing microbes goes through air

passages (nasal turbinates, oropharynx, larynx)– Microbes reaching lower respiratory system face

powerful epithelium sweeping action– Colonization requires adhesion mechanisms

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Other

No term for urinary or genital entry

By bypassing epithelial tissue, microbes can cause disease without penetrating deep into tissues– Cholera, whooping cough, infection of urinary

bladder

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Penetration into Deeper Tissues

Very few organisms can penetrate unbroken skin (worms are an exception)

Some organisms can penetrate epithelial tissue; for example:– S. pneumoniae, Treponema pallidum

Normally after some injury to tissue (many times caused by a virus)

– Viruses, by receptors

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Carried in by Macrophage

Alveolar macrophage trap organisms in lung– Normally carry upward on ciliary epithelium– Some cases, can carry deeper into tissues

Some organisms can live, grow in macrophage:– Legionella– Bordetella pertussis– HIV (via virus-laden macrophage from semen)

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Penetration by Other Means

Insect bites: numerous viral and protozoan diseases

Cuts and wounds: don’t normally lead to disease– Brushing teeth or defecating vigorously causes

minute abrasions of epithelium Organisms quickly cleared from blood by

reticuloendothelial system

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Penetration by Other Means

– Injury to internal tissue disrupts defense mechanisms and serious disease can result; for example

Subacute bacterial endocarditis– Devastating before antibiotics– Caused by oral streptococci that became implanted on

heart valves damaged by rheumatic fever

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Penetration by Other Means

Organ transplants or blood transfusions– Jakob-Cruetzfeldt disease from transplanted

corneas– Cytomegalovirus from kidneys, probably in donor

kidney

Because immunosuppressive drugs are used, virus may be endogenous

Hepatitis B, HIV transmitted by blood

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Disease Causation

Why are organisms adapted to various locations?– Temperature optima; athletes foot yeast cannot

grow at 37°C– Oxygen requirements– Specialized factors important for causing disease

(i.e., virulence factors)– Virulence: degree of pathogenicity

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Virulence Factor Examples

Exotoxins Endotoxins Capsules IgA proteases Adhesins (pili) Motility

Invasive properties Ability to acquire iron Serum resistance Ability to survive inside

phagocytes

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Inoculum Size

Inoculum size can determine whether organisms cause disease

Normally, high number needed to cause disease/overcome defenses; e.g.

– Baths in contaminated hot tubs (veritable culture of bacteria—over one hundred million organisms per ml)

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Inoculum Size

Normally harmless organisms can overcome defenses; e.g.,

– People get boils all over body

If large number of organisms deposited in deeper tissues, infection usually results

– Surgeon preps area to reduce numbers

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Spread of Disease

General: spread only if overcome host defenses

Sometimes precedes, sometimes follows microbial multiplication– Precede: parasite causes malaria disseminated before

multiplication

– Follow: S. aureus multiplies locally before being disseminated

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Spread of Disease

Types:– Direct lateral propagation to contiguous tissues– Dissemination to distant sites

Characteristics:– Anatomical factors (e.g., ear infections)– Active participation by pathogens— enzymes

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Multiplication

Factors that affect– Microbial nutrition: body is very nutritious, but it

also has antimicrobial substances– Body contains very little free iron

Physical factors: temperature, etc.– Narrow temperature optima—prudence of lowering fever

by “take two aspirin and call me in the morning”

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Damage

General: type and intensity depend on specific organism and tissue

Types:– Mechanical: mostly result of inflammation– Cell death: depends on:

Which cells How many infected How fast infection proceeds

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Damage

Types, continued:– Pharmacological: toxins alter metabolism– Damage due to host responses

Inflammation can lead to destruction of neighboring cells Immune response