NPTEL – Biotechnology – Microbiology

Module 10 – Microbial Pathogenicity and Diseases

Introduction

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 leprosy. Koch's postulates are criteria
designed to establish a causal relationship between a causative microbe and a disease.
Four criteria that were established by Robert Koch to identify the causative agent of a
particular disease, these include:

1. The microorganism or other pathogen must be present in all cases of the disease
2. The pathogen can be isolated from the diseased host and grown in pure culture
3. The pathogen from the pure culture must cause the disease when inoculated into a
healthy, susceptible laboratory animal
4. The pathogen must be reisolated from the new host and shown to be the same as
the originally inoculated pathogen.

The changes to the host, manifested as a set of symptoms, may be due to the effect of
microbial products such as toxins or the result of the host’s immune reactions to the
presence of the bacteria. Pain, fever, redness and swelling are common symptoms of
bacterial disease.

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Fig. 1. Different infection stages of disease causing organisms

A pathogen is a microorganism that is able to cause disease in a plant, animal or

insect. 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. Bacteria may produce two types of toxins
called exotoxins and endotoxins. Exotoxins are released from bacterial cells and may act
at tissue sites removed from the site of bacterial growth. Endotoxins are cell-associated
substance. The bacterial toxins, both soluble and cell-associated, may be transported by
blood and lymph and cause cytotoxic effects at tissue sites remote from the original point
of invasion or growth.

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The diseases can be caused by:

 Bacteria: - These one-cell organisms are responsible for illnesses such as strep
throat, urinary tract infections and tuberculosis.
 Viruses:-Even smaller than bacteria, viruses cause a multitude of diseases —
ranging from the common cold to AIDS.
 Fungi: - Many skin diseases, such as ringworm and athlete's foot, are caused by
fungi. Other types of fungi can infect your lungs or nervous system.
 Parasites: - Malaria is caused by a tiny parasite that is transmitted by a mosquito
bite. Other parasites may be transmitted to humans from animal feces.
MICROBIAL PATHOGENICITY

Factors that Influence the degree of Pathogenicity and the Progression of

Infection and Disease

 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)

External factors (e.g., crowding; seasonal variations; hygiene, sanitation and

public health; food processing, storage and preparation; etc.

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.
Progression of Infection and Disease

Entrance (Portal of entry).

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 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

Colonization (Adherence; Adhesion; Attachment)

 Attachment/Adherence: Close association of bacterial cells and host cells

generally characterized by receptors and target sites.
 Surface Receptors/Target Sites: Receptor sites present on both hosts (Receptor)
and bacterial surfaces (Adhesins).
 Adhesins: Bind Specific Host Receptors often involve fimbriae as structural cell
component; Host cell receptors are often sugar moieties. The lectins are adhesin
specific for polysaccharide target receptor (sugar residues).
 Fimbriae (plural): Short hair-like protein (pilin) appendages extending outward
from the surface of certain bacteria.
 Pili (plural); Pilus (singular): Short hair-like protein (pilin) appendages
extending outward from the surface of certain bacteria and responsible for
bacterial conjugation.

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.

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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.

Prevention of Host Defenses:-

Some pathogenic bacteria are inherently able to resist the bactericidal components of host
tissues. For example, the poly-D-glutamate capsule of Bacillus anthracis protects the
organisms against cell lysis by cationic proteins in sera or in phagocytes. 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.

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.

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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.
Penetration into Host Cytoskeleton

Many a time the pathogen penetrates into host cytoskeleton and use actin of host cell to
penetrate and move within the cells of host. The invasins a surface proteins produced by
bacteria to control actin e.g. Salmonella rearrange actin to cause the cell membrane to
wrap around the microbe and take it into the cell (endocytosis) allows Salmonella to
penetrate intestinal epithelium e.g. Shigella and Listeria trigger endocytosis.

Damage to Host Cells:-

The damages to the host cell can be direct or indirect. The direct damages are: -
 Tissue damage, cell components and metabolic by-products, toxins and enzymes.
 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: - 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.

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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: - 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, tissue necrosis, shock and death e.g. endotoxic shock: critical
loss of blood pressure due to bacterial endotoxins (LPS).
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).

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 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

REFERENCES:

Text Books:

1. Jeffery C. Pommerville. Alcamo’s Fundamentals of Microbiology (Tenth Edition).

Jones and Bartlett Student edition.

2. Gerard J. Tortora, Berdell R. Funke, Christine L. Case. Pearson - Microbiology: An

Introduction. Benjamin Cummings.

Reference Books:

1. Lansing M. Prescott, John P. Harley and Donald A. Klein. Microbiology. Mc Graw

Hill companies.

2. Biology, Raven and Jhonson, 6th edition (2001)

3. Microbiology, Pelczar. M.J , Chan E.C.S, Kreig N.R, 5th edition (2007)

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