This document discusses host-microbe relationships and microbial pathogenesis. It begins by defining key terms like pathogenicity, virulence, and toxigenicity. It then describes how most microbes do not cause harm, while a few contribute to health or pose threats. Pathogens can establish infections through various mechanisms like toxin production, tissue invasion, or evading host defenses. Toxins are categorized as exotoxins, endotoxins, or exoenzymes. Exotoxins like AB toxins directly damage tissues. Colonization, invasion, and evasion of host defenses allow pathogens to replicate and spread infection. Microbes cause disease through direct damage by toxins or indirect activation of the host immune response.

1. Establishment of Disease and
Replication/Damage by Microbial
Agents
MB 315 MEDICAL MICROBIOLOGY
Dr Simpokolwe

2. Establishment of Disease

3. • At the end of this lecture, students should be
able to:
– Describe the host-microbial relationships.
– Define parasitic organism, parasitism, infection,
infectious disease, pathogenicity, virulence,
invasiveness, infectivity, pathogenic potential, and
toxigenicity.
– Discuss the factors that determine the outcome of
most host-parasite relationships?

4. Overview of Host – Microbial
Interactions
• Most microorganisms are not harmful
• Few contribute to health and fewer pose
direct threats to health
Normal microbial flora
• Microorganisms usually found associated with
human body tissue
• Humans are colonized by microorganisms at
birth

5. Host Microbe Interactions
• Bacteria are ubiquitous & we come in contact
with them on a daily basis
– Breathe in, ingest with food and drink, pick up on
skin
– Vast majority generate no ill effects
– Others slough off with dead epithelial cells
– Most that are swallowed die in stomach or are
– eliminated in faeces

6. • We are also protected by the friendly resident
microorganisms found throughout our body
• Relatively few are pathogens that cause
damage

7. • Some microorganisms very easily colonize the
warm, moist, nutrient rich environment on our
body
• In some cases, these normal flora are able to
overcome the bodies defenses, and cause disease
eg.
– Defenses such as anatomical barriers, non-specific
local responses (e.g., pH), non-specific inflammatory
responses & specific immune responses (e.g.,
lymphocytes)
• Organisms that can cause any noticeable damage,
invade tissue, or produce toxins

8. Anatomical Barriers
• Skin and mucous membranes provide
anatomical barriers to infection
– Also supply foundation for microbial ecosystem
– Microbial community offers protection from
disease- causing organisms

9. Normal Flora
• Also known as normal microbiota are
organisms that routinely reside on body’s
surfaces
– Relationship is delicate balance; some can cause
disease should opportunity arise
– Weaknesses or defects in innate or adaptive
defenses can leave individuals vulnerable to
invasion and are said to be immunocompromised

10. • Some Factors than can lead to
immunosuppression include:
1. Malnutrition
2. Cancer
3. AIDS
4. Surgery
5. Wounds
6. genetic defects
7. alcohol or drug abuse
8. organ transplants

11. Some aspects of normal flora include:
1. SOURCE OF INFECTIONS
May be source of opportunistic infections e.g. In
patients with impaired immune system.
2. IMMUNOSTIMULATION
a)They enable the body to produce antibodies which
may contribute to host defenses.
b)Some of these antibodies may cross react with
normal tissue components.

12. 3)PROTECTION FROM EXTERNAL INVADERS
Prevent other microbes from establishing
themselves by blocking receptors, competing for
essential nutrients or producing anti-bacteria
substances e.g. Fatty acids, peroxides.
4)NUTRITION
Some of the normal intestinal flora e.g. E. coli &
Bacteroids produce Vitamin K in the gut which is
available for use by host.

13. • Symbiosis is any type of a close and long-term
biological interaction between two different
biological organisms, be it mutualistic,
commensalistic, or parasitic.
– Intimate interaction between microorganisms and
human body is an example of symbiosis
– The players in symbiosis are referred to as
symbionts

14. • Symbiosis.
– All symbiotic relationships are dynamic, and shifts
among them can occur as indicated by the arrows.

15. Mutualism: both partners benefit
• Examples of benefits include:
a) in large intestine, some bacteria synthesize
vitamin K and B vitamins, which host can absorb;
b) bacteria are supplied with warmth, energy
sources

16. Commensalism -One partner benefits, other is
unharmed
– E.g Many microbes living on skin neither harmful nor
helpful, but obtain food and necessities from host
Parasitism - one organism benefits at expense of
other
• All pathogens can become parasites, but medical
microbiologists often reserve this term for
eukaryotic pathogens (e.g., protozoa, helminths)

17. Principles of Infectious Disease
• Colonisation refers to microbe establishing
itself on body surface
• Infection is the state produced by the
establishment of one or more pathogenic
agents in or on the body of a suitable host
• Infection may also be a parasitic relationship
between a microorganism and a host

18. Infection can either be:
• Subclinical or inapparent - symptoms do not
appear or are mild enough so go unnoticed
• Infectious – Yields noticeable signs & symptoms
– Symptoms are subjective effects (nausea, pain etc)
– Signs are objective effects (rash, swelling, pus
formation etc) experienced by the Patients
• Infection that causes impairment of body
function is called a disease

19. • One infectious disease may leave individuals
predisposed to developing a new disease
• Initial disease is termed primary infection
• Additional infections resulting from primary
infection are termed secondary infection (e.g.,
respiratory illness impairing mucociliary
escalator)

20. • Pathogens are organisms that can cause
disease in otherwise healthy individuals
– That pathogen is termed as a primary pathogen
• Microbes that cause disease when the body’s
defenses are weak or when the organism is
introduced to an unusual location are termed
opportunistic pathogen

21. • Pathogenicity
– pertains to the ability of a pathogenic agent to
cause disease by overcoming the host defenses
• Virulence
– refers to pathogen’s disease-causing ability

22. • Highly virulent organisms have high degree of
pathogencity
– The more virulent a pathogen is the more disease
promoting attributes it has
• These organisms are more likely to cause
disease e.g. Streptococcus pyogenes causes
disease from strep throat to necrotizing
fasciitis.

23. • Virulence factors are traits that allow
microbes to help it infect and cause disease.
– These may include:
• ability to adhere
• ability to overcome host defense
• ability to evade host defence.

25. Characteristics of Infectious Disease
• Communicable or contagious diseases easily
spread from one host to the other either
through direct or indirect contact
• Infectious dose is number of microbes
necessary to establish infection

26. • ID50 is the number of cells that infects 50% of
the population eg
– Shigellosis results from ~10–100 ingested Shigella
– Salmonellosis results from as many as 106
ingested Salmonella enterica serotype Enteritidis
• Differences partially reflects ability to survive
stomach acid

27. pneumoniae) serovar Typhimurium)
Percentage
of
mice
killed
Highly virulent Moderately virulent
organism organism
100 (Streptococcus (Salmonella enterica
80
60
40
20
101 102 103 104 105 106 107
Number of cells injected per mouse

28. • Attenuation - The decrease or loss of
virulence
• Toxicity - Organism causes disease by means
of a toxin that inhibits host cell function or
kills host cells
– Toxins can travel to sites within host not inhabited
by pathogen

29. Course of Infectious Disease
• Incubation period: time between infection and
onset
– Varies considerably - few days for common cold to
even years for Hansen’s disease (leprosy)
– Depends on growth rate, host’s condition, infectious
dose
• Illness: signs and symptoms of disease
– May be preceded by prodromal phase (vague
symptoms)

30. • Convalescence: recuperation, recovery from
disease
• Carriers may harbour and spread infectious
agent for long periods of time in absence of
signs or symptoms

32. Duration of Symptoms
• Acute infections: symptoms develop quickly,
last a short time (e.g., strep throat)
• Chronic infections: develop slowly, last for
months or years (e.g., tuberculosis)

33. • Latent infections: never completely
eliminated; microbe exists in host tissues
without causing symptoms
– Decrease in immunity may allow reactivation
– Chicken pox (acute illness) results from varicella-
zoster virus; immune response stops, but virus
takes refuge in sensory nerves, can later produce
viral particles resulting in shingles
– Tuberculosis, cold sores, genital herpes also
examples

34. Distribution of Pathogen
• Infections often described according to
distribution within the body
• Localized
– Infection limited to small area e.g. boil
• Systemic or generalized
– Agent has spread or disseminated throughout the
body
– Example = measles

35. • Toxemia
– Toxins circulating in blood
• Viremia
– Viruses circulating in blood
• Septicemia
– Acute life-threatening illness caused by infectious
agent or its products circulating in blood

36. Establishing the Cause of Infectious Disease –
Koch’s Postulates
• Koch's Postulates criteria for establishing the
fact that specific microbes cause specific
diseases
• Determined by Robert Koch in 1877 while
looking for the causative agent for anthrax

37. • Establishing the Cause of Infectious Disease -
Koch’s Postulates
• In order to determine that a microbe causes a
disease, the following postulates must be met
1. The microorganism must be present in every case
2. The organism must be grown in a pure culture from
diseased hosts
3. The same disease must be produced when a pure
culture of the organism is reintroduced into a
susceptible host.
4. The organism must be recovered from the
experimentally infected hosts

39. Replication/Damage by
Microbial Agents

40. • At the end of this lecture, students should be
able to:
• List the steps involved in the infection process
and pathogenesis of bacterial diseases.
• Describe the mechanism of microbial replication
and damage.
• Describe the general characteristics of exotoxins
& endotoxins.
• Discuss the biological effects of endotoxins &
exotoxins.

41. • Pathogenesis is the manner in which a disease
develops
• This may occur through foodborne
intoxication or by pathogens invading and
breaching the body’s barrier.

43. Microorganism mechanism of
Pathogenesis
• Produce toxins that are ingested
– E.g., Clostridium botulinum, Staphylococcus
aureus
• Colonise mucous membranes, produce toxins
– E.g., Vibrio cholerae, E. coli O157:H7,
Corynebacterium diphtheriae

44. • Invade host tissues, avoid defenses
– E.g., Mycobacterium tuberculosis, Yersinia pestis,
Salmonella enterica
• Invade host tissues, produce toxins
– E.g., Shigella dysenteriae, Clostridium tetani
• Pathogens and hosts generally evolve toward
balanced pathogenicity (e.g., myxoma virus
and rabbits)

45. Bacterial Pathogenesis

48. Adherence
• Specific Adherence
– A pathogen must usually gain access to host
tissues and multiply before damage can be done
• Hence they need to attach to specific tissues
and this is known as adherence

49. • Bacteria that initiate infection often adhere
specifically to epithelial cells through
macromolecular interactions on the surfaces
of the pathogen and the host cells
• Adherence can be facilitated by:
– Extracellular macromolecules. Examples:
1. slime layer,
2. capsule
3. Fimbriae or pili
4. Lipotechoic acid

50. Adherence

52. Invasion
• At this point microbes begin to invade the
host & produce a bacteraemia or viremia.
– Bacteraemia - presence of bacteria in the
bloodstream
– Viremia - presence of a virus in the bloodstream

53. • Pathogen Invasion
– Starts at the site of adherence
– May spread throughout the host via the
circulatory or lymphatic systems
– Microorganisms are exposed to many barriers
after introduction into the host.
– Some bacteria are able to cause disease while
remaining on the epithelial barriers, while many
need to penetrate that barrier.

54. • The invasion of a host by a pathogen may be
aided by the production of Bacterial
extracellular substances which act against the
host by breaking down defenses of the body.
• These are known as invasins

55. • Most invasins are proteins (enzymes) that act
locally to damage host cells and/or have the
immediate effect of facilitating the growth
and spread of the pathogen.
• Invasins usually act at a short range (in the
immediate vicinity of bacterial growth) and
may not actually kill cells as part of their range
of activity

56. Colonization
• Colonization is the establishment of the
pathogen at the appropriate portal of entry.
• The availability of nutrients is the most
important in affecting pathogen growth
Pathogens may grow locally at the site of
invasion or may spread throughout the body

57. • During colonization, the host begins to show
signs of septicaemia for infection to proceed
an infectious dose should be determined.
• Infectious dose is the minimal number of
microbes necessary to establish infection e.g.
10-100 for Shigella & 1,000,000 for Salmonella
are needed establish infection

58. Evasion of Host Defenses
• Pathogens invade and evade the host
defences by different mechanisms such as:
– Intracellular pathogens that live inside a host cell
– Avoid phagocyte recognition by producing
capsules prevents phagocytosis
– Producing membrane damaging toxins which can
kill phagocytes (e.g., leukocidins)
– Interfere with complement activation Survive in
the phagocyte

59. Damage & Disease to Host Tissue
• Damage can occur through direct or indirect
pathways.
• Direct methods produce toxins, which are
poisonous substances that produce toxaemia
within a host.

60. Toxins
• Toxins are bacterial products that directly
harm tissue or trigger destructive biologic
activities.
• Toxins and toxin like activities are degradative
enzymes that cause lysis of cells or specific
receptor-binding proteins that initiate toxic
reactions in a specific target tissue.

61. • In many cases toxins are responsible for
causing the characteristic symptoms of the
disease.
• Three categories of toxins are produced
– Exotoxin, Endotoxin & exoenzymes

62. Exotoxins
• Are soluble, heat-labile, proteins that usually are
released into damage.
• They are produced by both Gram-negative &
positive bacteria.
• They may travel from the site of infection to
other body tissues
• Three categories of exotoxins:
– Cytolytic toxins
– AB toxins
– Superantigen toxins

63. Characteristics of Exotoxins
• Synthesized by specific bacteria that often
have plasmids or Heat-labile proteins
inactivated at 60 to 80°C
• Among the most lethal substances known
(toxic in very small toxin)
• Associated with specific diseases and have
specific mechanisms of action

64. • Highly immunogenic and stimulate the
production of neutralizing antibodies called
antitoxins
• Easily inactivated by formaldehyde, iodine,
and other chemicals to form immunogenic
toxoids
• Unable to produce a fever in the host directly
• Often given the name of the disease they
produce (e.g., the diphtheria toxin)

65. Cytolytic Toxins
• Work by degrading cytoplasmic membrane
integrity, causing cell lysis and death
• Toxins that lyse red blood cells are called
hemolysins
• Staphylococcal a-toxin kills nucleated cells and
lyses erythrocytes

67. AB Toxins
• Consist of two subunits, A and B Work by
binding to host cell receptor (B subunit) and
transferring damaging agent (A subunit)
across the cell membrane
• Examples: diphtheria toxin, tetanus toxin,
botulinum toxin

68. • Clostridium tetani and Clostridium botulinum
produce potent AB exotoxins that affect
nervous tissue
– Botulinum toxin consists of several related AB
toxins that are the most potent biological toxins
known
– tetanus toxin is also an AB protein neurotoxin

69. Diphtheria Toxin

73. Exotoxins
• AB Toxins
• They include enterotoxins whose activity
affects the small intestine
• Generally cause massive secretion of fluid into
the intestinal lumen, resulting in vomiting and
diarrhea
• Example: cholera toxin

76. Superantigens
• Are a special group of toxins
• Activate large numbers of T cells to release
large amounts of interleukins, e.g. IL-1, TNF &
IL-2, causing life-threatening autoimmune-like
responses.
• Include the toxic shock syndrome toxin of S.
aureus, staphylococcal enterotoxins, and the
erythrogenic toxin A or C of S. pyogenes.

77. Endotoxin
• The LPS of the cell which is a toxin when
solubilized
• Generally less toxic than exotoxins
• Gram-negative bacteria release endotoxin
• At low concentrations, endotoxin stimulates the
development of protective responses Such as
fever, vasodilation, and the activation of immune
and inflammatory responses

80. Exoenzymes
• Enzymes that function outside the host cells
or tissues.
• These include:
– Coagulase - forms a fibrin clot that “hides” the
microbe from phagocytosis
– Hyaluronidase - breaks connective tissues down
– Fibrinase - breaks down blood clots to allow
pathogens to continue spreading).

82. Exiting the Host
• A pathogen must exit the body.
• This occurs through various routes.
– Examples include sneezing, coughing, diarrhea,
coitus, pus, blood, or insect bites.
• Survival Outside the Host

83. • Pathogen must now to survive in the
environment long enough to be transmitted to
another host.
• Some can survive for several weeks before a
new host is found.
• Others that survive in animal reservoirs or
require direct contact because they are fragile.

84. Pathogenesis of Viral Diseases
• The fundamental process of viral infection is;
• the expression of the viral replicative cycle in host cell
• The steps for the infectious process involving viruses are
that a virus must;
– Enter a host
– Contact and enter susceptible cells
– Replicate within the cells
– Spread to adjacent cells
– Cause cellular injury
– Engender a host immune response
– Be either cleared from the body of the host, establish a
– persistent infection, or kill the host
– Be shed back into the environment

85. Entry, Contact & Primary Replication
• The first step is the attachment and entrance of the
virus into a susceptible host and the host’s cells.
• Entry may be accomplished through one of the body
surfaces
• E.g. skin, respiratory system, gastrointestinal system,
urogenital system, or the conjunctiva of the eye).
• Other viruses enter the host by needle sticks, blood
transfusions and organ transplants etc.
• Some viruses replicate at the site of entry, Cause dx at
the same site & do not spread throughout the body.
• Others spread to sites distant from the point of entry
and replicate at these sites.

86. Viral Spread & Cell Tropism
• Mechanisms of viral spread vary, but the most
common routes are;
• the bloodstream and lymphatic system.
• In some instances, spread is by way of nerves (e.g.,
rabies virus, herpes simplex, and varicella zoster
viruses
• Viruses exhibit cell, tissue, and organ specificities & this
is called tropisms
• A tropism by a specific virus usually reflects the
presence of;
– specific cell surface receptors on the eukaryotic host cell
for that virus

87. Cell Injury & Clinical Illness
• Destruction of the virus-infected cells in the
target tissues & alterations in host physiology
are responsible for the development of viral
dx & clinical illness.
• The potential effects of viruses on individual
host cells are the result of a complex series of
events.

88. • There are four generally accepted patterns of a
viral infection.
– In lytic infections the virus multiplies and kills the host
cell immediately and new virions are released.
– In persistent viral infections the virus lives in the host
cell and releases small numbers of virions over a long
period of time.
– In latent infections, the virus resides in the cell but
produces no virions.
– Some viruses can transform the host cell into a cancer
cell that becomes the focal point for a tumour

89. • Host Immune Response
– Both humoral & cellular components of the immune
response are involved in the control of viral infections.
• Recovery from Infection
– The host will either succumb or recover from a viral
infection.
– Recovery mechanisms involve nonspecific defense
mechanisms & specific humoral and cellular immunity.
– The relative importance of each of these factors varies
with the virus and the disease

90. Virus Shedding
• The last step in the infectious process is shedding of
the infectious virus back into the environment.
• This is necessary to maintain a source of viruses in a
population of hosts.
• Shedding often occurs from the same body surface
used for entry.
• During this period, an infected host is infectious and
can spread the virus.
• In some viral infections, such as a rabies infection,
humans are dead-end hosts because virus shedding
does not occur.