1 Microbial Pathogenesis Medical Microbiology

2 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

3 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

4 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

5 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

6 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

7 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

8 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

9 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

10 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

11 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

12 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

13 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

14 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

15 Entry Defined Ingress of microbes into body cavities contiguous with outside

16 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

17 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

18 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

19 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

20 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

21 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)

22 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

23 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

24 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

25 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

26 Virulence Factor Examples Exotoxins Endotoxins Capsules IgA proteases Adhesins (pili) Motility Invasive properties Ability to acquire iron Serum resistance Ability to survive inside phagocytes

27 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)

28 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

29 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

30 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

31 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”

32 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

33 Damage Types, continued: – Pharmacological: toxins alter metabolism – Damage due to host responses Inflammation can lead to destruction of neighboring cells Immune response