Microbial Mechanisms of Pathogenicity
How microorganisms enter a host •
How microorganisms penetrate host defenses
•
How microorganisms damage host cells •

Microbial Mechanisms of Pathogenicity
Pathogenicity = is the ability of a pathogen to produce a disease by overcoming the defenses of the host
•
Virulence = is the degree of Pathogenicity •
Incubation period = is the period between • the entry of the microbe till the appearance of disease symptoms

Microbial Mechanisms of Pathogenicity
To cause disease , most pathogens must •
Enter the host •
Adhere to host tissues •
Penetrate or evade host defenses
Damage the host tissues •
Exit from the host •
•

Mucous membranes , conjunctiva , skin
Respiratory tract (inhalation) •
•
( Common cold ,pneumonia ,tuberculosis ,influenza ,measles )
Gastrointestinal tract (food ,water, fingers)
( poliomyelitis ,hepatitis A ,typhoid fever ,amoebic dysentery
,cholera ,giardiasis )
•
•
•
Genitourinary tract
(sexually transmitted diseases)
(HIV ,genital warts ,chlamydia ,herpes ,syphilis ,gonorrhea) •
•

Skin
Hair follicles ,sweat gland ducts ,larvae of the hookworm ,fungi
•
Inoculation through the skin & mucous membranes (injury)
Bites = rabies •
• Injection =malaria
Wound •
Parenteral route •
•

Adhere to host tissues
Adhesins or ligands == Surface • projections on a pathogen = glycoproteins or lipoproteins = associated with fimbriae
Adhere to complementary receptors on host cells = mannose
•

How pathogen penetrate host defenses
Capsules =some bacteria make • glycocalyx material that forms capsules around their cell wall
This increase the virulence of species
==prevent bacteria from being phagocytized
•
Streptococcus pneumoniae •

How pathogen penetrate host defenses
Cell wall components = some bacteria contain chemical substances that contribute to virulence
•
Streptococcus pyogenes = produce a • heat-resistant & acid-resistant protein = Mprotein =present in cell surface & fimbriae
=increase the virulence
M-protein mediates attachment of the bacteria to epithelial cells of the host & helps them resist phagocytosis by WBC
•

How pathogen penetrate host defenses
Mycobacterium tuberculosis can even multiply inside phagocytes
• waxy lipid = mycolic acid •
Mycolic acid increase virulence by resisting digestion by phagocytes
•

How pathogen penetrate host defenses
Enzymes = the virulence of some • bacteria is thought to be aided by the production of extracellular enzymes
= exoenzymes
==can digest materials between cells or digest blood clot
•

How pathogen penetrate host defenses
Coagulases = enzymes that coagulate (clot) the fibrinogen in blood
•
Staphylococcus ( some members) • protect the bacteria from phagocytosis

How pathogen penetrate host
• defenses
Other enzymes
Kinases •
Fibrinolysin •
Streptokinase • collagenase
IgA proteases = destroy IgA = antibody in mucosal surfaces
Neisseria gonorrhaeae
Neisseria meningitidis

How pathogen penetrate host defenses
Antigenic variation =some pathogen alter their surface antigens
•
Adaptive immunity = acquired = specific defensive response of the body to an infection or to antigen
•
In the presence of antigen the body • produces protein called antibody = bind to antigen and inactivate or destroy them

How pathogen penetrate host defenses by the time the body mounts an immune response against a pathogen
•
When the pathogen has altered its antigens and is unaffected by the antibodies
•
Neisseria gonorrhoeae
Influenza virus •
•

Penetration into the host cell cytoskeleton
= protein filaments
(microfilaments ,intermediate filaments & microtubules) that present in the cytoplasm of eukaryotic cells that provide support & movement

Penetration into the host cell cytoskeleton
** when microbes attach host cell by adhesins
•
**this triggers signals in the host cell that activate factors that can result in the entrance of bacteria
•
**this mechanism is provided by the host cell cytoskeleton
•

How bacterial pathogen damage host cell
Pathogen can damage host cell in four basic ways:
## by using the host`s nutrients •
•
## by causing direct damage •
## by producing toxins •
## by inducing hypersensitivity •

How bacterial pathogen damage host cell
Using the host cell nutrients siderophores
=protein secreted by some bacteria in order
• to obtain free iron
!!-iron is required for the growth of pathogenic bacteria
• !!-in human body the concentration of free iron is low = most of it is bound to iron transport protein (transferrin , ferritin & hemoglobin)
**** = bacteria secrete siderophore s in order to obtain free iron
•
•

How bacterial pathogen damage host cell
Direct damage =pathogens metabolized & multiply inside the host cell by using nutrients & produce waste products=destroyed = rupture
•
• the microbe released & spread to other tissues in greater number
•

How bacterial pathogen damage host cell
The production of toxins = poisonous substance produced by bacteria
•
Toxemia = the presence of toxins in the blood
•
Toxigenicity = the ability to produce toxins •

How bacterial pathogen damage host cell
Toxins =are primary factor contributing to the pathogenic bacteria
=when transported by blood or lymph can cause serious & some times fatal effects
•
• fever • cardiovascular disturbances diarrhea •
& shock •
•

How bacterial pathogen damage host cell
Toxins = can inhibit protein synthesis destroy blood cells •
= = vessels •
•
& disrupt the nervous system by causing spasms •
•
& •

How bacterial pathogen damage host cell
= are proteins = Gram
positive & Gram negative bacteria
====produced inside bacteria as a part of their growth & metabolism & are secreted into the surrounding medium or released following lysis

How bacterial pathogen damage host cel l
= are soluble in body fluids
= they can easily diffuse into the blood
= are rapidly transported through the body
•
•
Botulism •

How bacterial pathogen damage host cell
Antitoxins = antibody to toxins = provide immunity to exotoxins
•
Toxoid = altered exotoxin = exotoxins are inactivated by heat or by formaldehyde , iodine or other chemicals they no longer cause disease but can still stimulate the body to produce antibody
( antitoxins )
• vaccine tetanus

How bacterial pathogen damage host cell
Types of exotoxins •
+++ A-B toxins •
+++ membrane-disrupting toxins •
+++ superantigens •
A-B toxins =polypeptides = inhibits protein synthesis & kill the host cell
Diphtheria toxin •
•

How bacterial pathogen damage host cell
• membrane-disrupting toxins =cause lysis of host cells by disrupting their plasma membranes
Staphylococcus aureus = •

How bacterial pathogen damage host cell
Streptococci = hemolysin •
Streptolysins •
Streptolysin O (SLO) =is inactivated by • atmospheric O2
Streptolysin S (SLS) =is stable in an O2 environment

How bacterial pathogen damage host cell
Superantigens =bacterial proteins = antigen that activate immune system ===electing a large immune response=====large amount of proteins (cytokines) ==== give rise to a number of symptoms *fever *diarrhea
*nausea *vomiting •
*some time shock & even • death
•
Staphylococcal toxins •
==food poisoning •
•
==toxic shock syndrome •

How bacterial pathogen damage host cell
= are lipopolysaccharides
**the lipid A component of the cell wall of
Gram negative bacteria
•
## are part of the outer portion of the cell wall
•
**are released when Gram negative • bacteria die & their cell walls undergo lysis

How bacterial pathogen damage host cell
Antibiotics used to treat diseases caused by Gram negative bacteria can lyses the bacterial cell
•
===this reaction releases endotoxin •
====lead to an immediate worsening of the symptoms
•

Pyrogenic response caused by endotoxin == when gm – ve bacteria ingested by phagocytes – degradation & the release of toxin
==the endotoxin cause the macrophages to produce a cytokine = interleukin-1
==carried via the blood to hypothalamus=a temp control center in the brain
==prostaglandins released = reset the thermostat = high temp = fever

How bacterial pathogen damage host cell
Shock = any life-threatening decrease in blood pressure
•
Septic shock = shock caused by bacteria •
Endotoxic shock = Gram negative bacteria endotoxin
•

How bacterial pathogen damage host cell
Phagocytosis of Gram negative bacteria •
Phagocytes ---secrete polypeptide •
( tumor necrosis • factor) bind to many tissues in the body & alter the metabolism •
•
Damage blood capillaries –their permeability drop in blood • pressure
•

How bacterial pathogen damage host cell
Salmonella typhi == typhoid •
Proteus spp == urinary tract infection
== wound infection •
•
Neisseria meningitidis == meningitis •

Naming – according to the system that can be affected
• Neurotoxins = nervous system
Hepatotoxins = liver •
Nephrotoxins = urinary tract •
•

According to the disease •
Diphtheria toxin
Tetanus toxin •
Vibrio toxin •
•

Pathogenic properties of viruses
**viruses evade destruction by the host s immune response by:
•
---viruses can penetrate and grow inside of host cell
•
---viruses have specific attachment sites for receptors on their target cells
•
CD4 for HIV •

Cytopathic effects of viruses (CPE) = destruction , killing & death of host cells
•
**stop mitosis = cytocidal •
**inclusion bodies =viral parts ,nucleic acid or proteins in the cytoplasm or in the nucleus
Negri bodies=rabies •
•
•

**syncytium=giant cell •
**decrease immunity= measles •
**interferon production •
**chromosomal changes & contact inhibition
= oncogen =cancer causing genes •
=transformation = malignant cell •
•

• Symptoms of fungal infections can be caused by :
Capsules •
Toxins =inhibit protein synthesis •
Ingestion of toxins cause headaches , vomiting nausea
•
Allergic responses = molds growing in homes
•

Pathogenic properties of protozoa & helminths
Symptoms of protozoan & helminthic can be caused by
•
**damage to host tissue •
**the metabolic waste products of the parasite
•
**some protozoan change their surface • antigen while growing in a host thus avoiding destruction by the host antibodies

Pathogens have preferred portal of entry , they also have definite portals of exit
•
**respiratory tract = coughing ,sneezing •
**gastrointestinal tract =saliva , feces •
**genitourinary tract = genital secretions •

Normal Microbiota
Biofilms •
•
Infectious diseases •
Emerging Infectious diseases •

Masses of microbes & their extracellular products attach to living & non living surfaces == biofilms
Dental plaque on teeth •
Algae on walls of swimming pools •
Scum accumulates on shower doors •
•
Biofilms provide attachment & resistance to antimicrobial agents
•

Microbes adhere to particular surface that is typically moist & contain organic matter
•
Microbes multiply & secrete a glycocalyx glycocalyx = enzyme produced by bacteria convert glucose • into sticky • polysaccharide
• glycocalyx

Normal microbiota = normal flora
Pathology = is the science of diseases
Etiology = the causes of the disease •
Pathogenesis & Pathogenicity
Virulence •
•
•
Infection = invasion or colonization of the body by pathogenic microorganism = the presence of a particular type of
• microorganism in a part of the body where it is not normally found
E.coli
= normally in intestine ** urinary tract infection
•

Normal microbiota = normal flora disease = an abnormal state in the body , in which part or all of the body is not properly adjusted , or incapable of performing normal functions ====any change from a state of health
Infectious disease = caused by a microbe •

Normal microbiota = normal flora
Microorganisms -----few are pathogenic
-----some are benefit •
•
Humans are generally free of microbes in utero
•
Microbes being colonization in & on the surface of the body soon after birth
•

Normal microbiota = normal flora
The first contact is during delivery •
Lactobacilli ==become the predominant organism in the newborn
•
E.coli
== acquired from foods begin to inhibit large intestine & remain there throughout life
•

Normal microbiota = normal flora
14
The number of bacteria on the body =1x10
13
The number of body cells =1x10 •
•
•
•
Bacteria which are establish permanent residence inside or on the body without producing disease is called === normal microbiota or normal flora
•
Transient microbiota ==present for various periods & then disappear
•

Normal microbiota = normal flora
There are many factors that determine the distribution & composition of the normal microbiota
•
Nutrients •
Physical & chemical factors
Defenses of the host •
Mechanical factors •
•

Normal microbiota = normal flora
Nutrients == bacteria can colonize only those body sites that can supply the appropriate nutrients
•
Nutrients may be derived from secretary products of cells •
Body fluids
Dead cells
•
• food in gastrointestinal tract •
•

Normal microbiota = normal flora
Physical & chemical factors === temperature pH, O2 , CO2 •
•
Defenses =immune response=variety of molecules & activated cells that kill
• microbes or inhibit their growth or prevent adhesion & neutralize toxins

Normal microbiota = normal flora
Mechanical factors =may affect colonization by normal flora e.g.
•
•
Chewing action of the teeth remove microorganism attachment
G.I.T. – flow of saliva & digestive secretions
R.T –mucus membrane •
•
•

Normal microbiota = normal flora
Other factors that also affect the normal microbiota
Age •
• Nutritional status
Diet •
Health status
Disability •
•
• Climate\geography
Personal hygiene •
Life style •
•

Relationship between the normal microbiota and the host
Microbial antagonism ===competitive exclusion
====normal microbiota prevent pathogen from colonization === protect the host
By-----
Competing for nutrients
Producing harmful substance affecting the growth of the pathogen

Relationship between the normal microbiota and the host e.g.
•
Lactobacilli & the yeast Candida albicans
Vagina pH 4 •
•
E.coli
in the intestine produce bacteriocins
, that inhibit the growth of salmonella & shigella
•

Relationship between the normal microbiota and the host
Symbiosis ==the relation between normal microbiota &the host ==means living together
•

Relationship between the normal microbiota and the host commensalism
• One of the organism is benefited &the other is unaffected
• Corynebacteria- eye---mycobacteria-ear no apparent benefit or harm to the host mutualism
• Both are benefits
• E.co
li in intestine synthesize vitamins K ?& some B vitamins parasitism
• One organism Is benefited by deriving nutrients at the expense of the other
• disease

Relationship between the normal microbiota and the host
Probiotics ==are live culture application to exert beneficial effect
Microbes produce CD4 --- HIV •
•
The relationship (symbiosis) can change under certain condition
•

Opportunistic microorganisms
==microorganisms that do not cause disease under normal conditions but
• cause disease under special conditions
***the symbiotic relationship can be changed
•

Opportunistic microorganisms e.g.
•
E.coli
=harmless as long as it remains in the large intestine – but if it gains access
• to other body sites it may cause disease
Urinary bladder===urinary tract infection •
• Lung===pulmonary infection
Spinal cord===meningitis •
Wounds===abscesses •

Opportunistic microorganisms
AIDS is often accompanied by a common opportunistic infections
•
Because AIDS patients immune system is suppressed
•

Second Term Exam.
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