Al-Ahliyya Amman University

Faculty of Allied Medical Sciences

Microbiology Course
Dr. Hala Al Daghistani
 Unit 8

Pathogenesis of microbial infection

Microbiology-Pharmacy

Dr. Hala Al Daghistani

 Pathogenesis of bacterial infection
Initiation of the infectious process: The mechanisms that lead to the development of signs and
symptoms of disease.

Characteristics of bacteria that are pathogens include

 transmissibility
 Adherence to host cells
 Persistence
 invasion of host cells and tissues
 toxigenicity
 ability to evade or survive the host’s immune system
 Resistance to antimicrobials and disinfectants
Disease occurs if the bacteria or immunologic reactions to their presence cause sufficient harm to
the person.
• Adherence (adhesion, attachment): The process by which bacteria stick to the
surfaces of host cells.
• Carrier: A person or animal with asymptomatic infection that can be transmitted to
another susceptible person or animal.
• Infection: Multiplication of an infectious agent within the body. Multiplication of the
bacteria that are part of the normal flora is not considered an infection.
• Invasion: The process whereby bacteria, animal parasites, fungi, and viruses enter
host cells or tissues and spread in the body.
• Microbiota: Microbial flora harbored by normal, healthy
individuals.
• Nonpathogen: A microorganism that does not cause
disease;may be part of the normal microbiota.
• Opportunistic pathogen: An agent capable of
causingdisease only when the host’s resistance is impaired
• Pathogen: A microorganism capable of causing disease.
• Pathogenicity: The ability of an infectious agent to cause
disease. (See also virulence.)
• Virulence: The quantitative ability of an agent to cause
disease.
Toxigenicity: The ability of a microorganism to produce a
toxin that contributes to the development of disease.

Koch’s Postulates
1. The microorganism should be found in all cases of the
disease in question.
2. The microorganism should be grown in pure culture in
vitro (or outside the body of the host) for several
generations.
3. When such a pure culture is inoculated into susceptible
animal species, the typical disease must result.
4. The microorganism must again be isolated from the
lesions of such experimentally produced disease.
 BACTERIAL VIRULENCE FACTORS

Virulence factors are bacteria-associated molecules that are required for a bacterium to
cause disease while infecting eukaryotic hosts such as humans. A surprisingly large number
of virulence factors are encoded by prophage infecting bacterial pathogens, such as cholera
toxin, Shiga toxin, and diphtheria toxin
• Adherence Factors
• When bacteria enter the body of the host, they must adhere to cells of a tissue surface.
• The interactions between bacteria and tissue cell surfaces in the adhesion process are
complex. Several factors play important roles, including
• Surface hydrophobicity, covalent bonds, ionic bonds……
• Net surface charge (Bacteria and host cells commonly have net negative surface charges
and therefore repulsive electrostatic forces).
• Binding molecules on bacteria (ligands)- Host cell receptor interactions.
• Many bacteria have pili, thick rod-like appendages or fimbriae, shorter “hairlike”
structures that extend from the bacterial cell surface and help mediate adherence of the
bacteria to host cell surfaces.
Invasion of Host Cells and Tissues
• invasion of the host’s epithelium is central to the infectious process.
• When inside the host cell, bacteria may remain enclosed in a vacuole
composed of the host cell membrane, or the vacuole membrane may
be dissolved and bacteria may be dispersed in the cytoplasm.
• In many infections, the bacteria produce virulence factors that
influence the host cells, causing them to engulf (ingest) the bacteria.

• Note: Toxin production and other virulence properties are

generally independent of the ability of bacteria to invade cells and
tissues.

Toxins
Toxins produced by bacteria are generally classified into two groups:
exotoxins and endotoxins.
Lipopolysaccharides of Gram-Negative Bacteria
• The LPS (endotoxin) of gram-negative bacteria are bacterial cell wall
components
• The pathophysiologic effects of LPS are similar regardless of their bacterial
origin except for those of Bacteroides species
• LPS in the bloodstream is initially bound to circulating proteins, which then
interact with receptors on macrophages neutrophils and other cells of the
RES.
Proinflammatory cytokines such as IL-1, IL-6, IL-8, TNF-á are released
• Complement and coagulation cascades are activated.
• Clinically: fever, leukopenia, and hypoglycemia; hypotension and shock
resulting in impaired perfusion of essential organs (eg, brain, heart, kidney);
intravascular coagulation; and death from massive organ dysfunction.

Peptidoglycan of Gram-Positive Bacteria

• The peptidoglycan of gram-positive bacteria is made up of cross- linked
macromolecules that surround the bacterial cells.
• Caused vascular changes leading to shock
• PG is much less potent than LPS.
Enzymes
• Many species of bacteria produce enzymes that are not
intrinsically toxic but do play important roles in the infectious
process.
Tissue-Degrading Enzymes
• Lecithinase( lecithin degrading substances)
• Collagenase, which degrades collagen, the major protein of
fibrous connective tissue, and promotes spread of infection in
tissue.
• Coagulase, which works in conjunction with blood factors to
coagulate plasma. It contributes to the formation of fibrin walls
around staphylococcal lesions, which helps them persist in
tissues and may help protect them from phagocytosis or from
destruction within phagocytic cells.
• Hyaluronidases are enzymes that hydrolyze hyaluronic acid, a
constituent of the ground substance of connective tissue.
Streptokinase (fibrinolysin), This enzyme is able to dissolve coagulated
plasma and probably aids in the rapid spread of streptococci through tissues.
Many bacteria produce substances that are cytolysins— that is, they dissolve
red blood cells (hemolysins) or kill leukocytes (leukocidins).
Streptolysin O, for example, is produced by group A streptococci . caused
hemolysis for red blood cells from many animals. It is oxygen labile ,
antigenic. The same streptococci also produce oxygen-stable, serum-inducible
Streptolysin S, which is not antigenic.
 Antiphagocytic Factors

• Many bacterial pathogens are rapidly killed after they are ingested by
polymorphonuclear cells or macrophages. Some pathogens evade phagocytosis
or leukocyte by
• Adsorbing normal host components to their surfaces. E.g. S aureus has surface
protein A, which binds to the Fc portion of IgG.
• Other pathogens have surface factors that impede phagocytosis (eg, S
pneumoniae, N meningitidis) e.g. polysaccharide capsules.
• S pyogenes (group A streptococci) has M protein. N gonorrhoeae (gonococci) has
pili.
• A few bacteria (eg, Capnocytophaga and Bordetella species) produce soluble
factors or toxins that inhibit chemotaxis by leukocytes and thus evade
phagocytosis
 Intracellular Pathogenicity
Some bacteria (eg, M tuberculosis, Listeria monocytogenes, Brucella species, and Legionella
species) live and grow within polymorphonuclear cells, macrophages, or monocytes. The
bacteria accomplish this by several mechanisms:

• they may avoid entry into phagolysosomes and live within the cytosol of the phagocyte
• they may prevent phagosome–lysosome fusion and live within the phagosome
• they may be resistant to lysosomal enzymes and survive within the phagolysosome.
 Importance of Bacterial Biofilms
• A biofilm is an aggregate of interactive bacteria
attached to a solid surface or to each other by
exopolysaccharide matrix.
• A single species of bacteria may be involved or more
than one species may coaggregate to form a biofilm.
Fungi, including yeasts, are occasionally involved.
• After a biofilm is formed, quorum-sensing molecules
produced by the bacteria in the biofilm accumulate,
resulting in a modification of the metabolic activity of
the bacteria.
• The bacteria in the exopolysaccharide matrix may be
protected from the host’s immune mechanisms.
• Some of the bacteria within the biofilm show marked
resistance to antimicrobials compared with the same
strain of bacteria grown free living in broth
• Biofilms are important in human infections that are
persistent and difficult to treat.
 Transmission Routes
Several different classifications for the routes of transmission for
different infections exist. Common classifications include:
person-to-person spread
Airborne
Waterborne
food-borne
vector-borne infections.
For diseases that can spread from one person to the next, it is
often more useful to divide the infections into those directly and
indirectly transmitted . Most of the infections in the indirect
group can also spread through direct contact.
In fact, the diseases that are placed in the ‘indirect’ category are
really just the most infectious ones
.
 Airborne transmission include

A. Aerosol transmission (airborne transmission) are very small

droplets that are able to stay suspended in the air for longer periods
of time.
B. Droplets are large mucus or saliva particles heavier than air that fall
toward the ground as soon as they're expelled, and droplet
transmission typically occurs when a droplet containing pathogen
comes in contact with another person's eyes, nose or mouth.

Organization uses a particle diameter of 5 𝜇m to delineate between •

Based on size and persistence as an aerosol, the World Health

Airborne (≤ 5 𝜇m) , Droplet (> 5 𝜇m)

 Vectors
A vector is any living organism that can carry a disease-causing microbe, but
most commonly they are arthropods such as mosquitoes, flies, fleas, lice, and
ticks. A vector can carry a pathogen externally or internally.
it serves as a mechanical vector, carrying the microbe on its body from
one place to another.

Diseases such as malaria, plague, and Lyme disease are transmitted via
arthropods that harbor the pathogen internally. The vector either injects the
infectious agent while taking a blood meal, or deposits the pathogen when it
defecates on skin where it can be inoculated when the individual scratches
the bite (infected fleas inject Yersinia pestis while attempting to take a blood
meal ).

In the case of malaria, caused by species of the eukaryotic pathogen

Plasmodium, the mosquito not only transmits the parasite but also plays an
essential role in its reproductive life cycle. Such vectors are called
biological vectors . The pathogen multiplies to high numbers within this
vector.
 Resident flora

Bacteria that are normally found in host, normally

doesn't cause disease.
The human body is built by 10 trillion cells 100 trillion non-
pathogenic bacteria/microorganisms that reside in or on a human
body
Transient flora: Bacteria that can't survive continual in the host.
Microbiome : Collective genomes of all the microorganisms (bacteria, fungi and
viruses) that reside in a person, literally share our body space
Microbiome and metabolic activity
Gut microbiome: Produce hydrolytic enzymes - help our digestive system, Synthesize vitamins –
K, B2, B12 and folic acid
Opportunistic pathogen: Microorganisms that cause disease when the
immune system is suppressed, when microbial antagonism is reduced or
when introduced into an abnormal area of the body.
Certain normal flora is often responsible for nosocomial infections when
they are introduced into the body through such medical procedures as
surgery and catheterization.