BACTERIAL PATHOGENESIS

SBP3403
 Normal Flora of Human Body

• Normal flora are bacteria, fungi, and protozoa that live on

or within the bodies of animals and plants.

• Normal flora, by definition, do not cause disease in healthy

individuals. Instead, they are communalists or mutualists
to the host, not harming the host, but are beneficial.
 Benefits from normal flora to host

Colonization inhibition:
• pathogenic microorganisms are inhibited by
normal flora from colonizing healthy individuals .
• competing with pathogenic microorganisms for
nutrients
• competing with pathogenic microorganisms for
space
• producing toxins that are harmful to some
pathogenic microorganisms
• The presence of normal flora in a host site can make the
environment less suitable to colonization or invasion by
pathogenic microorganisms.

• For example: The lactobacilli which colonies the vagina

lower the pH of that environment thus making an
inhospitable habitat to numerous other colonizers or
pathogens.
Normal flora are found mostly:

1.on the skin

2.in the eyes
3.in the nose
4.in the mouth
5.in the upper throat
6.in the lower urethra
7.in the lower intestine
8.especially in the large intestine
• Amount and types of nutrients available
at that site
• Resistance to antimicrobial substances
like lysozyme, bile, fatty acids
• Conditions such as
• Dry:
• Moist: eg diphtheroids
• pH
Factors that
Environmental condition ( a predisposing
factor for opportunistic infection determine the
depends on
Age
composition of
Nutritional status usual microbial
Disease states
Drug or antibiotics effect
flora
Opportunistic infections by normal flora
are frequently encountered in
immunocompromised people rather than
normal population
Microbial flora of skin
 Skin a natural barrier for pathogens
 Fattyacids , lysozyme desquamation (shedding outer layers
of skin) of epithelium
 Profuse sweating, washing and bathing does not eliminate
flora (reduced, but immediately replaced)
 Aerobes and Anaerobes form synergistic infections:
gangrene, necrotizing fasciitis, cellulitis

Flora of Mouth
Streptococcus-predominant genus
Dental plaque consists of gelatinous glucans, facilitate acid producers
to attach to enamel.
S. Mutants and lactobacilli produce high acid
High conc of acid demineralize the adjoining enamel and initiate caries
Flora of Conjunctiva
Diphtheroids, S. epidermidis and non-hemolytic
streptococci, Neisseriae, Moraxella Sp
Tears contain lysozyme which controls opportunistic
infections
 Respiratory system

Upper RS
Mouth
Nasopharynx
Oropharynx
Larynx
Lower RS
Trachea
Bronchi
Pulmunory parenchyma URS: normal flora
Strep viridans
Such as mitis,
URS: pathogens
mutans, milleri,
H. influenzae, S.
sanguis and
pneumonia and
Moraxella
N. meningitidis
catarrhalis,
S. aureus
Neisseria,
dipthereiods
 Gastrointestinal tract
The acid pH of stomach resist most pathogen acquired from food.
Except spore phase and cysts of parasites.
Small and large intestines usually have similar flora (108 to 1011
bacteria/gram of solid food)
Facultative anaerobes gram-negatives make 90%
G+cocci, yeast and P. aeruginosa also present
Antibiotics may inhibit many organisms

Genitourinary tract
Kidney, bladder and fallopian tubes : free of microbes
Perineum and urethra are colonized
Vaginal flora consistent with hormonal changes and age.
Lactobacilli maintain a low pH, inhibiting many organisms
 Role of Microbial flora in the
pathogenesis of infectious diseases
•Cause diseases when habitat is disturbed
•When leaked or reach other areas’
•Immune suppression by drugs, chemotherapy, radiation
•Underlying diseases

Role of microbial flora in host defense

against infectious disease

Immunesystem is primed by contact with microbes

Germ free environment have poor immune system
Antibodies production is stimulated by microbes
Suppressed Immune system –more susceptible to pathogenic
species.
Without activation by microbes, APC, cytokines, Cell mediated
immunity (CMI) will not be developed
Examples of human normal flora (100
different species of microbes)
•a.Actinomyces spp. • J.Diptheroids
•b.aerobic micrococci • k.Enterobacter spp.
•c.Bacteroides spp. • l.Enterococcus spp.
•d.Bifidobacterium spp. • m.Escherichia coli
•e.Candida spp. • N.Fusobacterium spp.
• o.Hemophilus spp.
•f.Clostridium spp.
• p.Klebsiella spp.
•g.Citrobacter spp. • q.Lactobacillus spp.
•h.Corynebacterium spp. • r.Neisseria spp.
•i.Corynebacterium • s.Pityrosporum spp.
xerosis • t.Propionibacterium acnes
• u.Proteus spp.
Bacterial Pathogenesis
Pathogen: A biological agent that causes
illness
Infection: Invasion, multiplication and
colonization of pathogens in host which
further leads to disease
Disease: Abnormality of host when
infected with pathogens
Pathogenesis: The development of a
disease or the process how a disease is
developed.
Pathogenicity: The ability to cause
disease by particular bacterial species
Virulence: The degree of pathogenecity
Mechanism of bacterial pathogenicity or
challenges that microbes face before
causing an infection
Bacteria cause infection through 6
steps
Step 1: Find a suitable host
1.Direct transmission: person-to-person
touching, biting, kissing or sexual
intercourse, droplet sneezing, coughing,
spitting, singing or talking.
2.Indirect transmission: (a) through vehicle
such as thermometers, drinking glasses, toys,
bedding and eating utensils. Water, food,
drinks and biological products, such as blood
or plasma. (b) Vector-borne transmission
(i)external transmission: Shigella from feces to
food by flies (no growth during transit)
(ii)internal transmission: malaria parasite
(grows during transit)
Step 2: Attachment and colonization
(a)pathogen when comes near the
host attaches the host through
special molecular reaction
(b)compatible protein complexes,
some on the host and some on the
microbe, recognize and bind to one
another.
(c)attachment is specific and
restricted to particular host or site.
 Step 3: Invasion of host defenses

1) Pathogens fight to escape from host

defenses
2) express proteins that kill phagocytes
that have come to destroy them
3) Pathogens often express enzymes that
weaken surrounding host tissues,
making it easier to spread to new
areas.
4) Some develop resistance to common
antibiotics, allowing them to continue
infection even after treatment.
 Step 4: Harm the host
• production of toxin
• simply by their growth and in some
cases,
• vigorous inflammatory response of the
host against the pathogen.

Step 5: Exit from host

•Exit from the host and look out new
host
•When the conditions are no more
favorable
 Step 6:Survival outside host until
find new host to infect
• ability to survive away from the host
• leads to microbe's transmission
• need proper elimination
• treatment or vaccine against the microbe. eg: smallpox
virus
• microbe that is able to survive and grow outside the host is
impossible to eradicate the disease. eg:Corynebacterium
diphtheriae can exist outside the host and therefore, keeping
high levels of immunity via vaccination is still important
even though diphtheria has been virtually eliminated from
the human population in the U.S.
Major determinants in pathogenesis or
virulence factors that damage the host
Capsules (outer layer): It is found in many bacteria, made
up of polysaccharides. Capsule acts as protective layer for
bacteria protects them from engulfment of eukaryotic cells
such as macrophages.

Production of exotoxins: exotoxins are toxins secreted by

bacteria. It causes damages to host by destroying cells or
disrupting normal cellular metabolism.
•For example: leukotoxins produced by bacteria destroy
phagocytes or WBC, eg Clostridium botulinum,
•cholera toxin from Vibrio cholerae causes cholerae,
•tetanus toxin from Clostridium tetani causes tetanus.
Invasive enzymes
•enzymes that helps in penetration of tissues
•Breaks the primary or secondary defenses of
•eg Hyaluronidase: this enzyme attacks the interstitial cement of connective
tissue by depolymerizing hyaluronic acid
•Collagenase: breaks down collagen, the framework of muscles
•Neuraminidase: degrades the neuraminic acid (also called sialic acid), an
intercellular cement of the epithelial cells of the intestinal mucosa.
•Streptokinase and staphylokinase are produced by streptococci and
staphylococci, respectively. Kinase enzymes convert inactive plasminogen to
plasmin which digests fibrin and prevents clotting of the blood.
•Pili and fimbriae:
•Appendages that stretch out from the prokaryotic cell into
the environment
•Bridge between pathogen and host cytoplasm delivering
toxins
Fimbriae: for attachment only
•Pathogenicity islands
•continuous stretches of DNA containing genes important for
the microbes ability to cause disease
Bacterial Pathogens
 Staphylococcus aureus
•Causes skin infections, eye infections, food-borne illness etc
•Leading cause of nosocomial infections : Infections acquired
in the hospital
Resistant strain are called as Methicillin resistant
Staphylococcus aureus (MRSA)
Nosocomial or Hospital MRSA (HAMRSA): Usually multiple
drug resistant ie resistant to many drugs
•Community acquired MRSA (CAMRSA): acquired from
community, usually not multiple drug resistant, but highly
virulent or pathogenic.

Properties of S. aureus
•Common inhabitants/colonizers of nose and skin
•Gram positive cocci, approximately 1 μm in diameter,
•occur in clusters resembling grapes (morphology is
important)
•Coagulase producers, catalase-positive
 Clinical manifestations
• pus-forming infections as well as food poisoning and
toxic shock syndrome
• superficial infections (boils, stye) to tissue infections
(pneumonia, meningitis and urinary tract infections)
and deep-seated infections of the bones and heart.
• remain localized due to the action of the immune
system (host response inflammation), fever, swelling,
the accumulation of pus and tissue necrosis.
• S. aureus gains access to the bloodstream, bacteremia
and sepsis
• Produce toxin: food poison (enterotoxin)
• Toxic shock syndrome: menstruation and the use of
tampons colonization of the cervix or vagina with S.
aureus and the production of a toxin fatal, high fever,
diffuse rash, peeling of the skin and low blood
pressure
 Mechanism of pathogenesis

Surface proteins - colonization of host tissues

Invasins- bacterial spread in tissues (leukocidin,
hyaluronidase);
Capsule, Protein A -surface factors that inhibit
phagocytic engulfment
Carotenoids, catalase production -substances
that enhance their survival in phagocytes
Membrane-damaging toxins that lyse eukaryotic
cell membranes (hemolysins, leukotoxin and
leukocidin).
•Protein A binds to IgG in different orientation,
makes it difficult for phagocytes to engulf and
destroy the bacteria
•nucleases, proteases, lipases, hyaluronidase
and collagenase, convert local host tissues into
nutrients for growth.
•virulence factors are analogous to those for S.
pyogenes and serve similar functions.
•Toxins: Exfoliative toxin (ET) causes the
scalded skin syndrome in neonates, widespread
blistering and loss of epidermis.
•Staphylococcal enterotoxins causes food
poisoning, 14 enterotoxins differ in genetic
makeup
•Toxic shock syndrome toxin (TSST) (super
antigens)
••Gram
Gram staining
staining
••Biochemical:
Biochemical: coagulase
coagulase test
test
••Antibiotic
Antibiotic susceptibility
susceptibility test
test
••Immunology:
Immunology: enterotoxins
enterotoxins
••Molecular
Molecular test:
test: genes
genes
••Beta
Betalactam
lactam
antibiotics
antibioticsfor
fornon-
non-
MRSA,
MRSA,community
community
MRSA
MRSA
••Vancomycin
Vancomycinforfor
MRSA
MRSAor ornosocomial
nosocomial
strains
strains