Microbial pathogenicity

1. MICROBIAL PATHOGENICITY AND DISEASES
Pathogenicity is the ability to produce disease in a host organism. Microbes express their
pathogenicity by means of their virulence, a term which refers to the degree of pathogenicity of
the microbe. Hence, the determinants of virulence of a pathogen are any of its genetic or
biochemical or structural features that enable it to produce disease in a host. The relationship
between a host and a pathogen is dynamic. The outcome of such a relationship depends on the
virulence of the pathogen and the degree of resistance and susceptibility of the host, due to the
effectiveness of the host defense mechanisms.
Two qualities of pathogenic microbes by which they cause disease to the host:
1. Invasiveness is the ability to invade tissues. It consists of colonization, production of
extracellular substances which facilitate invasion and ability to bypass or overcome host
defense mechanisms.
2. Toxigenesis is the ability to produce toxins.
FACTORS INFLUENCING PATHOGENICITY
Factors that Influence the degree of Pathogenicity and the Progression of Infection and Disease
are
● Host factors: Age, sex, ethnicity, nutrition (diet), hormonal status; personal hygiene and
immune status; Underlying disease or medical condition; Antibiotic or drug usage; Presence
of foreign object (e.g., splinter, catheter, sutures, etc.); Innate differences between hosts
● Microbial factors: Bacterial virulence factors; Inoculum size (dosage)
▪ Numbers of Invading Microbes:
The chances of causing diseases increase as the numbers of invading pathogens
increases. This expressed by infectious dose (ID50) and lethal dose (LD50).
▪ The ID50 (Infectious Dose) is the number of microbes required to produce infection
in 50% of the population. The ID50 is different for different pathogens i.e. different
ID50 for different portals of entry for the same pathogen.
▪ The LD50 (Lethal Dose) amount of toxin or pathogen necessary to kill 50% of the
population in a particular time frame.
● External factors (e.g., crowding; seasonal variations; hygiene, sanitation and public health;
food processing, storage and preparation; etc.

2. STEPS OF PATHOGENSIS
To cause disease a pathogen must:
● Gain access to the host.
● Adhere to host tissues.
● Penetrate or evade host defenses.
● Damage the host, either directly or accumulation of microbial wastes.
Fig. Different infection stages of disease causing organisms
BACTERIAL PATHOGENESIS
Although the vast majority of bacteria are harmless or beneficial, quite a few bacteria are
pathogenic. Pathogenic bacteria are bacteria that cause bacterial infection. One of the bacterial
diseases with highest disease burden is tuberculosis, caused by the bacterium Mycobacterium
tuberculosis, which kills about 2 million people a year, mostly in sub-Saharan Africa.
Pathogenic bacteria contribute to other globally important diseases, such as pneumonia,
which can be caused by bacteria such as Streptococcus and Pseudomonas, and food borne
illnesses, which can be caused by bacteria such as Shigella, Campylobacter, and Salmonella.
Pathogenic bacteria also cause infections such as tetanus, typhoid fever, diphtheria, syphilis, and

3. PROGRESSION OF INFECTION AND DISEASE
1. ENTRANCE ( PORTAL OF ENTRY )
● Mucous membrane: - is most common route for most pathogens. The mucous
membranes are respiratory tract, gastrointestinal tract, urinary/genital tracts and
conjunctiva.
● Skin (keratinized cutaneous membrane):- Some pathogens infect hair follicles, sweat
glands and colonize surface. But unless broken, skin is usually an impermeable barrier to
microbes.
● Parenteral route: - penetrate skin, punctures, injections, bites, cuts, surgery and deposit
organisms directly into deeper tissues.
The microbes must enter through preferred portal of entry in order to cause disease. But some
can cause disease from many routes of entry
2. COLONIZATION
The first stage of microbial infection is colonization: the establishment of the pathogen at
the appropriate portal of entry. Pathogens usually colonize host tissues that are in contact with
the external environment. Organisms that infect these regions have usually developed tissue
adherence mechanisms and some ability to overcome or withstand the constant pressure of the
host defenses at the surface.
Bacterial Adherence to Mucosal Surfaces.
In its simplest form, bacterial adherence or attachment to a eukaryotic cell or tissue
surface requires the participation of two factors:
 a receptor and
 a ligand.
The receptors so far defined are usually specific carbohydrate or peptide residues on the
eukaryotic cell surface. The bacterial ligand, called an adhesin, is typically a macromolecular
component of the bacterial cell surface which interacts with the host cell receptor. Adhesins and
receptors usually interact in a complementary and specific fashion with specificity comparable to
enzyme-substrate relationships and antigen-antibody reactions.
Biofilms are formed when microbes adhere to a surface which usually moist and contains
organic matter. The microbe secretes glycocalyx allowing other microbes to adhere a large mass
is formed. The biofilms are resistant to disinfectants and antibiotics.

4. PREVENTION OF HOST DEFENSES:
1. Some pathogenic bacteria are inherently able to resist the bactericidal components of host
tissues.
● The outer membrane of Gram-negative bacteria is a formidable permeability barrier that is
not easily penetrated by hydrophobic compounds such as bile salts which are harmful to the
bacteria.
● Pathogenic mycobacteria have a waxy cell wall that resists attack or digestion by most tissue
bactericides.
● And intact lipopolysaccharides (LPS) of Gram-negative pathogens may protect the cells from
complement-mediated lysis or the action of lysozyme.
2. Enzymes (exoenzymes):- The microbes produce many enzymes to prevent host defenses
are-
 Coagulases: clot fibrin in blood to create protective barrier against host defenses.
 Kinases: dissolve clots (fibrinolysis) to allow escape from isolated wounds
e.g.Streptokinase (Streptococcus pyogenes) Staphylokinase (Staphylococcus aureus)
 Hyaluronidase: Hydrolyzes hyaluronic acid (‘glue' that holds together connective tissues
and epithelium barriers) allowing deeper invasion e.g. Clostridium species: allows them
to cause gangrene (tissue necrosis).
 Collagenase: breaks down collagen (fibrous part of connective tissue) for invasion into
muscles and organs e.g. Clostridium species
 IgA proteases : destroy host IgA antibodies found in mucous secretions to allow
adherence and passage at mucus membranes e.g. Neisseria species that infect CNS.
3. Antigenic Variation
There are many pathogens which alter its surface antigens to escape attack by antibodies
and immune cells e.g. Neisseria gonorrhoeae has many variety of Opa gene, which can alter one
is being expressed e.g. influenza virus constant genetic recombination between flu viruses
always new spike proteins.
3. DAMAGE TO HOST CELLS
The direct damages are:
● Tissue damage, cell components and metabolic by-products, toxins and enzymes.

5. ● Organ necrosis: - Sum of morphological changes indicative of cell death and caused by
the progressive degradative action of cellular components, metabolic by-products,
enzymes and/or toxins.
● Metabolic Effects: Pathogenic organisms can affect any of the body systems with
disruptions in metabolic processes.
Indirect Damage:
 Damage to host from excessive or chronic immune response (immunopathogenesis).
Production of Toxins
Toxins are poisonous substance produced by microbes tend to cause widespread
damage/disease in host may be necessary for virulence. There are two types of toxins produced
by bacteria.
Exotoxins:
Exotoxins produced inside the bacteria and either secreted or released following microbe
lysis and toxin genes are often found on plasmids or via lysogenic phages. The most exotoxins
are enzymes and function to destroy certain host cell parts or inhibit particular metabolic
functions or damage from toxin results in the particular signs or symptoms of a disease. The
named for the disease, type of cell attacked or organism that produces it e.g. tetanus toxin: causes
tetanus (contraction) of muscle. Three types of exotoxins:
 A-B toxins have two parts: A is the enzyme that disrupts some cell activity and B binds
surface receptors to bring A into the host cell e.g. botulinum & tetanus toxin.
 Membrane disrupting toxins cause lysis of the host cell by disrupting the plasma
membrane e.g. leukocidins: make protein channels in phagocytic leukocytes e.g.
hemolysins: make protein channels in RBCs (hemolysis: Steptococcus pyogenes).
 Superantigens bacterial proteins that cause proliferation of T cells and release of
cytokines and excessive cytokines can cause fever, nausea, vomiting, diarrhea, shock and
death (septic shock) e.g. toxic shock syndrome (Staphylococcus) e.g. enterotoxins:
Staphylococcal food poisoning.
Endotoxins:
Endotoxin is part of the outer membrane portion of the cell wall of gram negative
bacteria: Lipopolysaccharide (LPS) released when dead cells lyse in blood, causes macrophages
to release high levels of cytokines resulting in chills, fever, weakness, aches, small blood clots,

6. tissue necrosis, shock and death e.g. endotoxic shock: critical loss of blood pressure due to
bacterial endotoxins (LPS).
Models of action of toxins
Modeling has become a common used tool to predict modes of toxic action in the last
decade. The models are based in
 Quantitative Structure-Activity Relationships (QSARs), which are mathematical models that
relate the biological activity of molecules to their chemical structures and corresponding
chemical and physicochemical properties. QSARs can then predict modes of toxic action of
unknown compounds by comparing its characteristic toxicity profile and chemical structure
to reference compounds with known toxicity profiles and chemical structures.
It has been proposed that modes of toxic action could be estimated by developing a data set of
critical body residues (CBR).
 The CBR is the whole-body concentration of a chemical that is associated with a given
adverse biological response and it is estimated using a partition coefficient and
a bioconcentration factor. The whole-body residues are reasonable first approximations of the
amount of chemical present at the toxic action site(s). Because different modes of toxic
action generally appear to be associated with different ranges of body residues, modes of
toxic action can then be separated into categories. However, it is unlikely that every chemical
has the same mode of toxic action in every organism, so this variability should be
considered. The effects of mixture toxicity should be considered as well, even though
mixture toxicity it's generally additive, chemicals with more than one mode of toxic action
may contribute to toxicity.
MAJOR TYPES OF MODES OF TOXIC ACTION
There are two major types of modes of toxic action:
● non-specific acting toxicants and
● specific acting toxicants.
NON-SPECIFIC TOXICANTS
Non-specific acting modes of toxic action result in narcosis; therefore, narcosis is a mode
of toxic action. Narcosis is defined as a generalized depression in biological activity due to the
presence of toxicant molecules in the organism. The target site and mechanism of toxic action
through which narcosis affects organisms are still unclear, but there are hypotheses that support

7. that it occurs through alterations in the cell membranes at specific sites of the membranes, such
as the lipid layers or the proteins bound to the membranes. Even though continuous exposure to
a narcotic toxicant can produce death, if the exposure to the toxicant is stopped, narcosis can be
reversible.
SPECIFIC TOXICANTS
Toxicants that at low concentrations modify or inhibit some biological process by binding
at a specific site or molecule have a specific acting mode of toxic action. However, at high
enough concentrations, toxicants with specific acting modes of toxic actions can
produce narcosis that may or may not be reversible. Nevertheless, the specific action of the
toxicant is always shown first because it requires lower concentrations.
There are several specific acting modes of toxic action:
1. Uncouplers of oxidative phosphorylation.
Involves toxicants that uncouple the two processes that occur in oxidative
phosphorylation: electron transfer and adenosine triphosphate (ATP) production.
2. Acetylcholinesterase (AChE) inhibitors.
AChE is an enzyme associated with nerve synapses that it’s designed to regulate nerve
impulses by breaking down the neurotransmitter Acetylcholine (ACh). When toxicants bind
to AChE, they inhibit the breakdown of ACh. This results in continued nerve impulses across
the synapses, which eventually cause nerve system damage. Examples of AChE inhibitors
are organophosphates and carbamates, which are components found in pesticides
3. Irritants.
These are chemicals that cause an inflammatory effect on living tissue by chemical action
at the site of contact. The resulting effect of irritants is an increase in the volume of cells due
to a change in size (hypertrophy) or an increase in the number of cells (hyperplasia).
Examples of irritants are benzaldehyde, acrolein, zinc sulphate and chlorine.
4. Central nervous system (CNS) seizure agents.
CNS seizure agents inhibit cellular signaling by acting as receptor antagonists. They
result in the inhibition of biological responses. Examples of CNS seizure agents
are organochlorinepesticides.

8. 5. Respiratory blockers. These are toxicants that affect respiration by interfering with
the electron transport chain in the mitochondria. Examples of respiratory blockers
are rotenone and cyanide.
PATHOGENIC PROPERTIES OF VIRUS
 Viruses have mechanisms to evade host defenses viruses grow inside host cells to hide
from immune defense.
 Kill immune cells e.g. HIV – TH Cells.
 Cytopathic effects: - The visible effects of viral infection on host cell. Some effects will
kill the cell and some will just change the cells.
 Viruses stop DNA, RNA and/or protein synthesis e.g. Herpes virus block mitosis.
 Lysosomal autolysis of host cells e.g. Influenza: bronchiolar epithelium.
 Production of inclusion bodies (visible viral parts inside the cell) can identify a particular
virus e.g. Rabies virus: Negri bodies.
 Syncytium formation (neighboring cells fuse together) e.g. Varicella Zoster virus.
 Change in cell function e.g. Measles, production of interferons by host cell (triggers host
immune response), induce antigenic changes on host cell surface (triggers destruction of
infected cell by host immune response).
 Induce chromosomal changes, cell transformation: may activate or deliver oncogenes
resulting in loss of contact inhibition (cancer) e.g. Papilloma virus.
Eukaryotic Pathogens
Fungi
 They produce toxins causing allergies or disease e.g. -chronic sinusitis (black molds).
 Stachybotrys : headaches, vomiting, mental disturbance.
 Invasive systemic mycosis in immune compromised patients e.g. Candida.
 Mushrooms: mycotoxins may be hallucinogenic or deadly.
Protozoa
● They can grow inside host cells causing lysis e.g. Malaria (Plasmodium)
● They use host cells as food source and produce wastes that cause disease.
Algae
 It produces neurotoxin substances e.g. shellfish poisoning