Bacterial pathogenesis
Dr. Ibtisam Habeeb
Introduction to bacterial pathogenesis
• Infection: growth and multiplication of a microbe in or on the body with or without
the production of disease.
• A pathogen: is a term that refers to a microorganism that causes disease in an
organism.
• The capacity of bacterium to cause disease reflects the relative “pathogenicity”
• Virulence: is the measure of the pathogenicity of a microorganism.
• Pathogenesis refers both to the mechanism of infection and to the mechanism by
which disease develops.
Microorganism and host
Saprophytism – Living on dead or decaying organic matter.
Parasitism – Living on or within another living organism –
Commensalism – parasite lives on/in the host without causing any disease.
Symbiosis – mutually beneficial relationship
Opportunistic pathogen – The organism is generally harmless, but can cause disease when it gains access to other
sites or tissues.
Obligate pathogen – parasite always causes disease .
Infectivity – It is the capacity of the organism to penetrate the tissues of host, to survive the host defenses, and to
multiply and disseminate in host.
Sources of infection
• Sources of infection are animal and inanimate in nature:
• Animal sources
Normal flora
Animals in incubation period of disease
Animals with overt disease.
Convalescent carrier : In these person shedding of the pathogen occurs for varying periods after clinical recovery. The period
may vary from weeks to months.
Contact carrier or subclinical infections: They acquire pathogenic organisms from other animals suffering with infectious
disease without contracting the disease themselves. Such animals are called as contact or subclinical carriers. The carrier state
may be temporary for a few days or lasting for months.
• Inanimate sources (fomites)
• Contaminated utensils, feed and water troughs, vehicles, etc.
Transmission
• Disease can be transmitted by direct or indirect contact:
• Direct contact
contact with discharges or aerosols from the animal.
Coitus.
Vertical transmission from mother to offspring.
• Indirect contact
Organisms excreted by the infected animal are carried in/on various
vehicles like feed, water, litter, clothing, footwear, farm house products
and by-products, equipment's, personnel, logistics, air or dust. Such
contaminated objects are called as fomites.
Contaminated instruments may also spread the infection.
Routes of entry
Inhalation
Ingestion
Inoculation through the skin or mucous membrane
Coitus or artificial insemination.
Transplacental / in ovo
Hospital acquired infections - nosocomial infections.
Physician induced infections - iatrogenic infections.
Pathogenicity
• Pathogenicity: The ability to cause
disease, the factors effect bacterial
pathogen are:
1-virulence factors
2- number of initial organisms
3- immune status
• A disease ensues when the balance
between bacterial pathogenicity and host
resistance is upset.
• Pathogenic bacteria can be grouped into three categories on the basis of their
invasive properties for eukaryotic cells:
Extracellular ( Vibrio cholerae)
Obligate Intracellular ( Chlamydia)
Facultative Intracellular (Salmonella)
Terminologies
• Bacteraemia
Bacteraemia is the presence of bacteria in blood.
The pathogenic organisms may gain entry in to a blood capillary or venule actively or passively from the initial site
of entry.
Once in blood stream the organism can cause localized infection or spread to various parts of the body, e.g.
Leptospires reach the kidneys following bacteraemia.
Organisms can directly gain access to the blood by first infecting the lymphoid system.
• Septicaemia
Septicaemia is the presence of actively multiplying bacteria in the blood.
One of most severe septicaemia is anthrax in which the number of bacteria in blood may often exceed the
erythrocytes in blood.
Septicaemic infections often start as localized infections that later become generalized, e.g, Streptococcal
pharyngitis,.
• Toxaemia
Toxemia is the presence of toxins in blood.
• Bacteria cause disease by 2 basic mechanisms:
1. Direct damage of host cells
2. Indirectly by stimulating exaggerated host inflammatory/immune
response.
Virulence
• Virulence: is the measure of the pathogenicity of an organism to cause
disease; usually used to describe the difference in disease causing
capability between two different strains of the same species.
• Virulence can be expressed as LD50 (lethal dose for 50% of the
inoculated hosts) or ID50 (infectious dose for 50% of the inoculated
hosts).
Virulence factors
• Virulence factors: The factors produced by a microorganism and induce pathology in a host are called virulence factors.
These factors help pathogen to
(1) invade the host,
(2) cause disease (3) evade host defenses.
• Virulence factors are classified into two categories –
1. Virulence factors that promote bacterial colonization of the host:
Adherence Factors
Invasion and/or Spreading Factors
Compete for iron and other nutrients;
Evasion of host immune responses
2. Virulence factors that damage the host:
Exotoxins
Endotoxins
Genetic basis for virulence
• Virulence factors in bacteria may be encoded on chromosomal
DNA, bacteriophage DNA, plasmids, or transposons. For
example, the heat-labile enterotoxin (LTI) of E. coli is plasmid
encoded, and diphtheria toxin of C. diphtheriae is coded by
phage.
• Virulence factors are acquired by bacteria by vertical or
horizontal gene transfer
Bacterial virulence factors that promote colonization in the
host
• Factors for contact with host cells:
1. Bacterial motility - e.g., non-motile
mutants of Vibrio cholerae are less virulent
than the motile wild types.
2. Bacterial enzymes - e.g., Streptococcus
pyogenes produces streptokinase that
facilitate spread of the bacterium by
liquefying the fibrin clot
Factors for adherence with host cells - adhesins
• Adhesins are proteins found on the cell wall of various bacteria that
bind to specific receptor molecules on the surface of host cells and
enable the bacterium to adhere intimately to that cell in order to
colonize and resist physical removal, e.g. common fimbriae,
capsule, biofilm, and pilus.
Adherence factors - Pili (fimbriae)
Spreading factors
• "Spreading Factors" are a family of bacterial enzymes that affect the physical properties of tissue matrices and intercellular
spaces, thereby promoting the spread of the pathogen.
Hyaluronidase - depolymerize hyaluronic acid, the interstitial cement substance of connective’ tissue; produced by
Staphylococci,.
Collagenase - breaks down collagen; produced by Clostridium histolyticum and Clostridium perfringens.
Neuraminidase - degrades neuraminic acid (also called sialic acid) present on epithelial cells of the mucosa; produced by
Vibrio cholerae, Shigella dysenteriae, P. multocida, and M. haemolytica
Streptokinase and Staphylokinase - convert inactive plasminogen to plasmin which digests fibrin.
Edema Factor of B. anthracis - adenylate cyclase activity promote bacterial invasion.
Invasions
Some bacteria have mechanisms by virtue of which they
initiate phagocytosis in non-phagocytic cells for
invasion by:
binding to some receptor on cell.
Some pathogens can utilize actin fibres intracellularly to
move through host cells (transcytosis).
Invasins may also mediate uptake of bacteria into
professional phagocytic cells in a way that bypass
normal phagosome formation.
Transcytosis
The ability to compete for nutrients and iron
• Bacteria compete for nutrients by synthesizing specific transport systems or cell wall
components capable of binding limiting substrates and transporting them into the cell.
Siderophores--low MW compounds that chelate iron with very high affinity, eg. E.coli
Direct binding of host transferrin, lactoferrin, ferritin, or heme by bacterial surface
receptors, eg. Yersinia species
Exotoxins that lyse host cells (can be used to obtain other nutrients as well), eg.
haemolysins
Bacterial virulence factors that helps in evasion of immune
response
• Evasion of Innate Immune Responses
Invade or remain confined in regions inaccessible to phagocytes. e.g. the lumen of
glands and the skin are not patrolled by phagocytes.
Avoid provoking an inflammatory response.
Hide the antigenic surface of the bacterial cell. eg, S.aureus produces coagulase which
clot fibrin on the bacterial surface
Inhibit chemotaxis of phagocytes, e.g. Streptococcal streptolysin, fractions of suppresses
neutrophil chemotaxis
Inhibit ingestion by phagocytes, e.g. capsule inhibit recognition and engulfment by
phagocytes
Resistance to complement mediated lysis (serum resistance), e.g. capsule, LPS.
Capsules blocking the attachment of bacteria to phagocytes
Evasion of adaptive immune defenses
Antigen masking - Some bacteria are able to coat themselves with host proteins such as fibrin,
fibronectin, lactoferrin, and in this way avoid antibodies.
Antigenic switching or phase variation - one way certain bacteria can evade antibodies is by
changing the adhesive tips of their pili or vary other surface proteins so that antibodies already
made will no longer "fit.“
Staphylococcus aureus produces protein A while Streptococcus pyogenes produces protein G.
which non-specifically binds IgG with very high affinity
Immunoglobulin proteases - Bacteria such as Neisseria gonorrhoeae and Enteropathogenic E.
coli produce enzymes that degrade the antibodies found in body secretion (IgA).
Staphylococcus aureus resisting opsonization via protein A
• The Fc portion of the antibody IgG, the
portion that would normally binds to Fc
receptors on phagocytes, instead binds to
protein A on Staphylococcus aureus.
• In this way the bacterium becomes coated
with a protective coat of antibodies that do
not allow for opsonization.
Bacterial virulence factors that damage the host
• Virulence factors that damage the host include:
The cell wall components that bind to host cells causing them to synthesize
and secrete pro-inflammatory cytokines and chemokines.
Toxins.
Induce autoimmune responses.
Bacterial cell wall components that promote synthesis and
secretion of inflammatory cytokines and chemokines
LPS of Gram-negative bacteria, and teichoic acids and glycopeptides of Gram-positive bacteria
induces cytokine production and secretion
These cytokines, such as TNF-alpha, IL-1, interleukin-6 IL-6, IL-8, and lead to activation of the
complement pathways and the coagulation pathway.
In some bacteria, lipoproteins in the outer membrane may also play a role in leading to excessive
cytokine production.
