This document defines key terminology related to microbial pathogenicity and discusses various concepts including: 1. It classifies microbes as saprophytes, parasites, commensals, and pathogens. 2. It describes the infection process and different types of infections such as primary, secondary, and nosocomial. 3. It explains mechanisms of microbial pathogenicity including routes of transmission, infective dose, evasion of host defenses, adhesion, invasion, and the role of toxins and pathogenicity islands.

1. MICROBIALPATHOG
ENICITY
DR. MANISH TIWARI
SMC UNNAO

2. Terminologies
Terminology Explanation
Saprophytes Free-living microbes that live on dead or decaying organic
matter.
Parasites Microbes that live on a living host, derive nutrition from the
host and also cause harm to the host. They are of two types-
microparasites (bacteria, viruses, fungi and protozoa) and
macroparasites (helminths).
Commensals Harmless microbes that harbour on a living host as normal
flora of the host without causing any injury to the host

3. Pathogens Microbes capable of causing disease. Represents only
a very small proportion of the microbial world.
Opportunistic
pathogens
Causes disease only in immunocompromised people.
Infection Process in which a pathogenic organism enters, establishes
itself, multiplies and invades the normal anatomical barrier
of the host; resulting in disease.
Infectious
disease
Infectious diseases are caused by pathogenic
microorganisms, such as bacteria, viruses, parasites or
fungi; the diseases can be spread, directly or indirectly,
from one person to another.
Colonization Pathogenic organism enters, multiplies but does not
invade, and neither causes disease or nor elicits specific
immune response. (not same as normal flora).

4. Classification of infections
1. Primary infection
2. Re infection
3. Secondary infection
4. Focal infection (or focal sepsis)
5. Cross-infections
6. Nosocomial infections
7. Iatrogenic (or physician induced)

5. 1. Primary infection :- Initial infection with a pathogenic
microorganism in a host.
2. Reinfection:- Subsequent infection by the same parasite in
the host.
3. Secondary infection:- New pathogen sets up an infection in a
host whose immunity is already lowered by a pre-existing
infection.

6. 4. Focal infection (or focal sepsis):- Indicates a condition where, due
to infection at localised sites (such as in the appendix or tonsils),
generalised effects are produced.
5. Cross-infections:-When in a patient already suffering from a
disease a new infection sets up from another host or another
external source.
6. Nosocomial infections:-Cross-infections occurring in hospitals are
called nosocomial infections.
7. Iatrogenic (or physician induced):-Refers to the infections induced
by the professional activity of the physician or other health care
workers resulting from preventive, diagnostic, treatment.

7. source
1. Endogenous infections:- Source of infection is within the
body, either normal flora if breeches the anatomical barrier, or
endogenous reactivation of a latent infection.
2. Exogenous infections:- Source is outside the host's own body.

8. Asymptomatic infection
 Infection that is active but does not produce noticeable
symptoms.
Symptomatic or apparent or clinical infections:-
 Acute infection- here, the symptoms last for a short term
period.
 Chronic infection- symptoms persist for a long period.

9. 3. Latent infection:- refers to an infection that is inactive or
dormant or in hidden form; but capable of reactivating later.
4. Atypical infection:- the usual manifestations of the disease are
not present. Instead, atypical symptoms may be present

10. 1. Endemic:-Endemic is derived from Greek en meaning
in and demos meaning people. It is used to describe a disease
that is present at an approximately constant level within a
society or country.
2. Epidemic:-is the rapid spread of disease to a large number of
people in a given population within a short period of time.
3. Pandemic:-Infection that spreads rapidly over large areas of
the world.
4. Sporadic :- refers to a disease that occurs infrequently and
irregularly.

11. SOURCES AND RESERVOIR OF INFECTION
 Source and reservoir are not always synonymous.
 Source-
o The source of infection refers to the person, animal, or
object from which a microorganism is transmitted to the
host.
 A reservoir is the natural habitat in which the organism lives,
multiplies.

12. SOURCES AND RESERVOIR OF INFECTION
 The term source and reservoir may be same for many
organisms but are not always synonymous. For example,
o In tetanus infection- the reservoir and source of the agent
(Clostridium tetani) are same, i.e. the soil.
o In hook worm infection- the reservoir is man, but the source
of infection is the soil contaminated with the larva of hook
worm.
o In typhoid fever, the reservoir may be a case or carrier, but
the source of infection is usually contaminated food &
water.

13. Types
1. Human reservoirs.
2. Animal reservoirs.
3. Non living reservoirs

14. Human reservoirs.
1. Communicable diseases
2. Cases or patients
3. Carrier
4. Incubatory carriers
5. Healthy carriers
6. Convalescent carrier
7. Temporary carriers
8. Chronic carriers

15. 1. Communicable diseases:-Diseases that can be spread from
one person to another are called. Human sources may be
either cases or carriers.
2. Cases or patients:- Persons in a given population identified
as having a particular disease.
3. Carrier:-Persons/animals that harbour the infectious agent in
the absence of any clinical symptoms and shed the organism
from the body via contact, air or secretions and risk
transmission (inadequate treatment or immune response).

16. 4. Incubatory carriers:- Person shed the organism during the
incubation period of disease (usually occurs in the last few
days of incubation period) e.g. measles, mumps, polio,
diphtheria, pertusis, hepatitis B, influenza, etc
5. Healthy carriers:-Subclinical cases who develop into
carriers without suffering from overt disease, e.g., polio,
cholera, salmonellosis, diphtheria, meningococcal meningitis,
etc.
6. Convalescent carrier:- One who has recovered from the
disease and continues to harbour and shed the pathogen from
his body.

17. 7. Temporary carriers:-shed the organisms for less than six
months (incubatory, healthy and convalescent carriers).
8. Chronic carriers:- shed the organisms for indefinite period.
E.g. in hepatitis B, typhoid fever, malaria, gonorrhoea, etc.

18. 2. Animal reservoirs.
 Zoonoses - Disease and the infections which are transmitted to man
from vertebrates.
 Common examples include-
o From animals- rabies (from dog), yellow fever (from monkeys),
leptospirosis (from rodents), and influenza (from pigs), etc.
o Birds may be source of infection for various diseases like
influenza, Chlamydophila psittaci infection (psittacosis),
histoplasmosis etc.
 Amplifying host - Vertebrate reservoir in which the organism
multiplies exponentially, e,g. pigs in Japanese B encephalitis.

19. 3. Non living reservoirs
 Soil and inanimate matter can also act as reservoir/source of
infection.
 Example soil may harbour the agents of tetanus, anthrax and
some intestinal helminths.

20. MODE OF TRANSMISSION
 Microorganisms may be transmitted from the reservoir or
source to a susceptible host in different ways :
1. Contact
2. Inhalation
3. Airborne
4. Ingestion
5. Inoculation
6. Transmission of Blood borne infections
7. Vector borne (mechanical or biological)
8. Vertical transmission

21. o Direct contact from skin and mucosa of an infected
person- through unclean hand, kissing, or sexual contact.
 e.g. Common cold, skin and eye infections and agents of sexually
transmitted diseases (STD) such as HIV, Neisseria gonorrhoeae,
Chlamydia trachomatis and Treponema pallidum etc.
o Indirect contact through the agency of fomites, which are
inanimate objects such as clothing, toys, etc which may be
contaminated by a pathogen and act as a vehicle for its
transmission.
 e.g. face towels shared by various persons may lead to spread of
trachoma.

22. Inhalation transmission
 Agents causing respiratory infections are acquired by
inhalational route.
 These organisms are shed into the environment by patients in
secretions from the nose or throat during sneezing, coughing or
speaking in the form of droplets.

23. Air borne transmission
 Droplet nuclei (<10 µm size) can remain suspended in air for long
periods, and can act as source of infection.
 Droplet (dust) transmission- Larger droplets (>10 µm size) travel for
a short distance, settle down on clothing and other objects and
become a part of the dust.
o Respiratory viruses (e.g., influenza, parainfluenza virus,
 Airborne (droplet nuclei) transmission-When the droplet is small (1-
10 µm), it can travel a long distance; can infect any person it finds on
its way. Primary contact with the source is not necessary.
o Organisms transmitted through this route include agents causing
tuberculosis, measles and chickenpox virus.

24. Ingestion
 Intestinal infections like cholera, dysentery, food poisoning and
most of the parasitic infections are acquired by ingestion of
food or drink contaminated by pathogens.
 Food borne infections occur mostly through carriers engaged
in handling or preparation of food and contaminating the food
stuffs.
 The water supply may get contaminated with the faeces of the
patients or carriers

25. Inoculation
 Pathogens, in some instances, may be inoculated directly into
the skin or tissues of the host.
 Animal bite- for example, rabies virus is inoculated directly by
bite of a rabid animal.
 Inoculated directly into tissues-Spores of Clostridium tetani
present in the soil, get deposited directly into the host tissues
following severe wounds leading to tetanus.

26. Transmission of Blood borne infections
 Blood borne infections such as hepatitis B, hepatitis C and HIV
may be transmitted by-
o Needle prick and other sharp injuries (with contaminated
sharps)
o Blood transfusion
o Intravenous drug abuse (through contaminated needles)

27. Vector borne (mechanical or biological)
 Arthropod vectors such as mosquitoes, flies, fleas, ticks, mite,
and lice are the vectors that transmit many diseases. Vector
may be of two types.
 Mechanical vectors: These carry the microorganisms (which
do not multiply) and transmit them to the eatables.
 Biological vectors: The pathogen multiplies in the body of the
vector, often undergoing part of a development cycle in it. (e.g.
female Anopheles mosquito in malaria; Culex mosquito in
filariasis).
 Extrinsic incubation period: After the entry of pathogen into
the vector, the time required for the vector to become infective
is called extrinsic incubation period.

28. Vertical transmission
 Refers to transmission of infection from mother to the fetus.
 It may be categorized into-
o Transplacental transmission –Infection occurs via the
placental barrier; leads to abortion, miscarriage or stillbirth. If
babies are born, they suffer from congenital malformations.
Such infections are known as teratogenic infections. Examples
include TORCH infections-
 Transmission via the birth canal without causing congenital
malformation in the baby- Examples include-Group B
Streptococcus, Neisseria gonorrhoeae, Chlamydia trachomatis,
Viruses-Hepatitis B, Hepatitis C and HIV, Listeria
monocytogenes.

29. MECHANISM OF MICROBIAL PATHOGENICITY
 Bacterial pathogenicity depends upon the sum total of several factors
as described below:
1. Route of transmission of infection
2. Infective dose of the organism
3. Evasion of the local defences
4. Adhesion
5. Adherence
6. Invasion
7. Toxins
8. Pathogenicity islands
9. Other bacterial products

30. Route of transmission of infection
 Route of transmission of infection plays a crucial role in the
pathogenicity of certain bacteria.
 Some bacteria, such as streptococci, can initiate infection
whatever be the mode of entry.
 Others can survive and multiply only when introduced by the
optimal routes.

31. Infective dose of the organism
 Infective dose of the organism is referred to as the minimum
inoculums size that is capable of initiating an infection.
 Low Infective dose
o Shigella : very low (as low as 10 bacilli); Cryptosporidium
parvum : very low (10 to 30 oocysts); Escherichia coli
O157:H7 (< 10 bacilli); Entamoeba coli and Giardia : few
cysts; Campylobacter jejuni (500 bacilli)
 Large Infective dose
o Escherichia coli (106 - 108 bacilli); Salmonella (102 – 105
bacilli); Vibrio cholerae (106 - 108 bacilli).

32. Evasion of the local defences
 Skin, mucus, ciliated epithelium, and secretions containing
antibacterial substances (e.g. lysozyme) are the natural barriers
of the human and animal hosts that prevent microbial entry.
 However, these barriers are sometimes broken.

33. Adhesion
 Adhesion of the bacteria to body surfaces is the initial event in
the pathogenesis of the disease. It is mediated by specialized
molecules called adhesins which bind to specific host cell
receptors.
o Adherence prevents the bacteria from being flushed away
in secretions and also facilitates bacterial invasion into the
host cells.
o Fimbriae or pili are the most important adhesins present in
some bacteria. They directly bind to the sugar residues
(glycolipids or glycoproteins) on host cells.

34. Invasion
 Invasion refers to entry of bacteria into host cells, leading to
spread within the host tissues.
 Highly invasive pathogens produce, spreading or generalised
lesions (e.g. streptococcal infections), while less invasive
pathogens cause localised lesions (e.g. staphylococcal abscess)
 Some pathogens though capable of causing fatal diseases lack
invasiveness but remain confined to the site of entry and
produce disease by elaborating a potent toxin e.g. Clostridium
tetani.

35. Toxins
Endotoxins
 They are the lipid A portion of lipopolysaccharide. They are
present as an integral part of the cell wall of Gram negative
bacteria.
 They are released from the bacterial surface by natural lysis of
the bacteria and are responsible for various biological effects in
the host.

36. Biological effects of Endotoxins
a. Macrophage activation
b. Complement activation
c. Endothelial activation
d. Coagulation pathways activation
e. Platelet activation
f. Mast cell activation
g. In Gram negative septicemia

37. Exotoxins
 They are heat labile proteins; secreted by certain species of both
Gram positive & Gram negative bacteria and diffuse readily into
the surrounding medium.
 High potency- Exotoxins are highly potent even in minute
amounts.
 Used for vaccine-Exotoxins can be converted into toxoids by
treatment with formaldehyde.
 Specific action- They are highly specific for a particular tissue
e.g. tetanus toxin for CNS. They have specific pharmacological
activities.

38. Difference between endotoxin and exotoxins
Feature Endotoxins Exotoxins
Nature Lipopolysaccharides Proteins
Source Part of cell wall of Gram negative
bacteria
Secreted both by Gram positive &
negative bacteria; diffuse into
surrounding medium
Released by Cell lysis
Not by secretion
Actively secreted by the bacteria
Heat stability Highly stable Heat labile destroyed at 60oC
Mode of
action
↑IL-1 and TNF Mostly enzyme like action

39. Feature Endotoxins Exotoxins
Effect Non-specific (fever, shock,
etc)
Specific action on particular
tissues
Tissue affinity No Specific affinity for tissues
Fatal dose Only large doses are fatal More potent, even smaller
doses- fatal
Antigenicity Poorly antigenic Highly antigenic
Neutralisation by antibodies Ineffective Neutralized by specific
antibodies
Used for vaccine No effective vaccine is
available using endotoxin
Toxoid forms are used as
vaccine; e.g. tetanus toxoid

40. Pathogenicity islands
 Large genomic islands located in the chromosomal regions of
some bacteria containing sets of genes encoding numerous
virulence factors
 Pathogenicity islands have been detected in some bacteria such
as Shigella, Salmonella, Vibrio cholerae, Yersinia pestis,
Staphylococcus aureus, uropathogenic E.coli, Helicobacter
pylori, etc.

41. Bacterial secretary system
 Secretion in bacteria refers to the translocation of effector
molecules such as proteins, enzymes or toxins (such as cholera
toxin) across the cell membrane from cytoplasm to its exterior.
 Secretion is a very important mechanism for bacterial survival
and pathogenesis.
 There are at least five specialized secretion systems described
especially in Gram negative bacteria .

42. 1. Coagulase
2. Fibrinolysins
3. Hyluronidase
4. Leucocidins
5. Hemolysins

43. Bacterial appendages:
 Capsulated bacteria such as pneumococci, k. pneumoniae,
h. influenzae are not rapidly phagocytosed. Some bacterial
surface antigen such as Vi antigen of s. typhi and k antigen
of e. coli which is help in the phagocytosis and they are
lytic activity of the complement activity.

44. Biofilms
 These are also well organised microcolonies of bacteria ,
that are enclosed of EPM( Extracellular Polymer
Matrix)or Glycocalyx.
 Biofilm are divided into two types:
 Monomicrobial Biofilms
 Polymicrobial Biofilms