Host Microbe Interactions

Host Defense Virulence:

microrganisms
State of Health Tankeshwar Acharya
Lecturer
 Class objectives

● Understand the concept of host pathogen interaction

and its types
● Understand the concept of pathogenicity and
virulence
● Know different microbial virulence factors
● Understand sources and routes of Infections
● Understand different types of infections
Normal Flora Locations & Species

Note that much of those

locations not mentioned are
sterile in healthy individuals.
● Bacteria are constantly associated with our body
surfaces
● Normal flora/commensals
● Resident flora Vs. Transient flora

SYMBIOSIS: Neutral, antagonistic or synergistic relationship

between two dissimilar organisms living in close association
with each other;
 Types of Interactions

Mutualism: Both partners benefit (+/+)

● E. coli produces vitamins, K & B and
bacteriocins (chemical that ward off
harmful species)
● Large intestine provides nutrients

Commensalism: One partner benefits, other is neutral (+/0)

The ability of a microorganism to live on the external or
internal surfaces of the body without causing disease.
Parasitism (+/-): One partner benefits while the other
is harmed
Many protozoan, helminths, bacteria, virus and fungi.
 ● A microorganism is a pathogen if it is capable of causing
disease.
Pathogenicity vs. Virulemce

● Pathogenicity: the quality of producing disease or the

ability to produce pathologic changes or disease
● Some organisms are highly pathogenic (highly virulent) but
some rarely cause disease.
● Virulence
● quantitative measure of pathogenicity and
● measured by the number of organisms required to cause
disease.
● LD50: Number of microorganisms/toxins needed to kill
half the hosts.
● ID50: Number of organisms needed to cause infection in half
the hosts.
● The infectious dose of bacteria depends primarily on their
virulence factors. eg dose of Salmonella vs. Shigella for
causing Enteric fever and Dysentery respectively

●Opportunistic pathogens are those that rarely cause disease in

immunocompetent person but can cause serious infection in
immunocompromised individuals.
 ● People get infectious diseases when microorganisms
overpower our host defenses.
Why do People Get Infectious disease?

● Organisms perspectives:
Two critical determinant in overpowering the host are
1. Number of organisms to which host is exposed.
Greater the number of organisms, the greater is the
likelyhood of infection.
2. Virulence of these organisms.
Small number of highly virulent organisms can cause
disease. The virulence of an organism is determined by its
ability to produce various virulence factors.
The gene that codes for virulence may be located in
Pathogenicity islands (PAIs) in bacterial
chromosome, Plasmids or in bacteriophage they are
carrying.
Host perspectives in Infectious disease

● Main arms of our host defenses are:

● Innate immunity (Non specific defense)
● Acquired immunity (Specific immune defense):
Antibody mediated and Cell Mediated.
● A reduction in the functioning of any component of
our host defenses shift the balance in favor of the
organism and increase the chance that an infectious
disease will occur.
● Examples: Opportunistics infections in AIDS, Cancer,
Immunosuppression conditions.
 ● Infection: A process in which an organism enters, establishes
itself, and multiplies in the host producing signs and
symptoms of disease.
Types of Bacterial Infections

● An infection is epidemic if it occurs much more frequently

than usual;
● It is pandemic if it has a worldwide distribution
● An endemic infection is constantly present at low level in a
specific population.
● Some infection leads to overt disease, but many are
inapparent or subclinical.
● Some infections result in a latent state.
● Some infections lead to a chronic carrier state: In which
organisms continue to grow with or without producing
symptoms in the host. E.g. Chronic carriers, eg. Typhoid
Mary
 Steps of bacterial infections

1. Transmission from an external source into the portal

of entry
2. Evasion of primary host defenses
3. Adherence to mucous membrances
4. Colonization by growth of bacteria at the site of
adherence
5. Disease symptoms caused by toxin production or
invasion accompanied by Inflammation
6. Host responses, both nonspecific and specific
(immunity) during steps, 3, 4 and 5
7. Progression or resolution of the disease
 Incubation Stage: No signs and symptoms
Illness:
a. Prodomal Stage: First signs and symptoms
b. Clinical Stage: Peak of characteristic sign and symptoms of
infection or disease
Stages of Infection

Convalescent stage: Full recovery of surviving host or chronic

infection develops or Death
Sources and routes of infection
 Modes of Transmission

Microorganism
Sources (Reservoirs) Direct: Direct contact between Reservoir
Humans and Hosts
Animals
Food/ Water Indirect: Transmitted to Host
Air via Intervening Agents
Huma
Soil n Host

Intervening Agents:
Vectors: Animals, Insects,
Other Humans
Vehicles- Water, food, air,
medical devices, various
other inanimate objects
Modes of Transmission of Infections
● Direct/Contact
● Trauma or Surgical Procedure
● Needlestick
● Arthropod Bite
● Inhalation
● Ingestion
● Sexual Transmission
● Congenital/Transplacental
Infections due to bite/trauma

e.g. Wound Infections, Zoonoses etc.

Fecal oral Transmission: (via food
and water) bacteria, especially Gram
Negative bacilli, viruses such as polio
and Hepatitis A protozoans such as
Entamoeba and Giardia

Airborne Transmission: Bacteria

that cause strep throat, diphtheria,
pertusis viruses such as influenza,
measles, mumps, rubella,
chickenpox and the common cold ,
fungi such as Histoplasma and
Pneumocystis
Sexually Transmitted Infections: Such as
Bacterial vaginosis, Chlamydia, Genital HPV
Infection, Genital Herpes, Gonorrhea, Pelvic
Inflammatory disease, Syphilis, HIV etc.
Host Defense Mechanisms
Mouth: Mucosal Defense against
RM Pathogens Nasopharynx:
Sloughing of cells
Flow of Saliva RM
Lysozyme Secretions:
Lysozymes,
Phagocytes),
Lungs:
Ciliated Cells
Macrophages

Stomach:
Low PH
Proteolytic
Colon: Mucus,
Enzymes Sloughing of
Cells
Small Intestine: Abundant
Fast Flow
Resident
Mucus
microflora
Sloughing of Cells
Bile Salts Bile Salts
 Vagina:
Low PH
Resident
Microflora
Bladder: Flushing
action of Urine
Low PH
Physical Barrier of
Urethra

Urethra
Urine Flow

Defense Against Urinary Tract Infections

Host defense mechanisms Contd…
● Phagocytosis
● Inflammation
● Complement System
● Immune System
● Antibody Mediated Immunity
● Cell Mediated Immunity
Bacterial virulence factors
● Adherence factors
● Invasion of Host Cells and Tissues
● Toxins
● Exotoxins
● Cytotoxins, Neurotoxins, Enterotoxins etc.
● Endotoxins: Lipopolysaccharides of Gram Negative
Bacteria
● Enzymes
● Tissue degrading enzymes
● IgA1 proteases
Bacterial Virulence Factors
Bacterial virulence factors
● Antiphagocytic factors
● Intracellular pathogenicity
● Antigenic heterogeneity
● Bacterial secretion system
● The requirement for iron
● The Role of Bacterial biofilms
Microbial strategies for colonization

● Survival Against Environmental conditions

● Localisation in moist areas
● Protection within ingested or inhaled debris
● Expression of specific metabolic characteristics (e.g. salt
tolerance)
● Attachment and Adherence to Host cell Surfaces
● Motility
● Production of Substances that compete with host for
acquisition of essential nutrients (eg. Siderophores for
capture of iron)
● Ability to coexist with other colonizaing
microorganisms
 Adherence factors
Once bacteria enter the body of the host, they must
adhere to cells of a tissue surface otherwise they would
be swept away by Mucus or body fluids.
Factors that help to mediate
adherence are:
1. Hair like appendages
(Pili/Fimbriae) e.g. in E coli

2. Lipoteichoic acid and

Protein F cause
adherence of S.
pneumoniae in 3. Pili and Opacity associated proteins
buccal epithelial (Opa) in Neisseria gonorrhoeae
cells.
Invasion of host cells and Tissues
● Entry of bacteria in to host cells
● Bacteria produce virulence factors that influence host
cells to engulf the bacteria.
● C. diphtheriae is able to invade epithelium of
nasopharynx
● Invasion plasmid antigens (IpA-D) in Shigella
● Yersinia adhere to the host cell membrane and cause it
to extrude protoplasmic projections and then get
engulfed by the host cells.
● Legionella pneumophila: Inhibits phagolysosome
fusion and multiply within the vesicle.
 Avoidance of Phagocytosis
Capsule is external to the
cell wall of several
important pathogens such
as:
•S. Pneumoniae
•H. Influenzae
•N. meningitidis
Other Antiphagocytic factors
•M protein of Group A
Streptococci (Streptococcus
pyogenes)
•Protein A of S. aureus prevents
complement activation
 ● Collagenase: It degrades collagen thereby allowing
Bacterial Enzymes as Virulence Factor

the bacteria to spread through subcutaneous tissue.

● Hyaluronidase: It degrades Hyaluronic acid.
● Coagulase: It accelerates the formation of a fibrin clot
which may protect bacteria from phagocytosis by
walling off the infected area.
● Leukocidins: It destroy both neutrophilic leukocyte
and macrophages.
Bacterial Enzymes as Virulence Factor

● Lecithinase: Breaks lecithin

● Streptokinase (Fibrinolysin)
● Cytolysins: eg. Hemolysin, leukocidins.
● IgA Protease: Cleave secretory IgA antibodies.
 Bacterial Toxins
●Exotoxins and Endotoxins
●Endotoxin:
Lipopolysaccharides
Lipoteichoic acid
●Exotoxins
oEnterotoxins (eg: Shigella, Vibrio)
oCytotoxins (Shigella, EHEC)
oNeurotoxins (Clostridium, Bacilus cerus)

●DIY: Difference between exotoxins and endotoxins

Microbial strategies for surviving the Immune System

● Pathogen changes antigens so that immune system is constantly

fighting a primary encounter
● Pathogen produces enzymes (e.g. proteases) that directly
destroys or inactivate antibodies.
● Pathogens invades and destroys cells involved in the immune
response.
● Pathogen survives, unrecognized, in host cells and avoids
detection by immune system

● Pathogen multiplies and invades so quickly that damage to host

is complete before immune response can be fully activated

● Pathogens covers its antigen with a capsule so that an immune

response is not activated
Pathogenicity islands (PAIs)

● Large group of genes that are associated with pathogenicity

and are located on the bacterial chromosome.
● The PAIs have one or more virulence genes and are
present in genome of pathogenic member of species but
absent in the nonpathogenic members.
● Virulence Characteristics coded by PAIs are
● Adhesions/fimbriae
● Enhanced iron uptake
● Biofilm production
● Cytolysin
● P-pilus formation
● Enterotoxins etc
 Thank you
Any Questions