Bacterial Pathogenicity and 

Pathogenesis of bacterial
diseases

• A pathogen- is a microorganism that is able to cause

disease in plant, animal and humans.
• Pathogenicity- is the ability to produce disease in
host organism
• Microbes express their pathogenicity by means of
their virulence, the term for the degree of the
pathogenicity of the microbe.
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The relationship between a host and a pathogen is dynamic,
since each modifies the activities and functions of the other.
• 
The outcome of such a relationship depends on:
 the virulence of the pathogen and
 the relative degree of resistance or susceptibility of the host,
mainly due to the effectiveness of the host defense
mechanisms
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 Mechanisms of Bacterial Pathogenicity

1. Invasiveness: the ability to invade tissues.

 encompasses mechanisms for
colonization (adherence and initial multiplication),
production of extracellular substances which
facilitate invasion (invasins) and
Ability to by pass or overcome host defense
mechanisms
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2. Toxigenesis: ability to produce toxins.

Bacteria may produce two types of toxins:

– exotoxins and

– endotoxins.

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 Exotoxins are released from bacterial cells and may act
at tissue sites removed from the site of bacterial
growth.
 Endotoxins are cell-associated substance. (classic
sense, endotoxin refers to the lipopolysaccharide
component of the outer membrane of Gram-negative
bacteria).
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 Bacterial pathogenesis

• Infection/entry

• Virulence factors

• Pathogenesis
• Escape of immune surveillance

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 Entry
Ingestion: Salmonella, Shigella, Vibrio, Clostridium etc..

Inhalation: Mycobacterium, Mycoplasma, Chlamydia etc..

Trauma: Clostridium tetani

Arthropod bite: Rickettsia, Yersinia pestis, etc.

Sexual transmission: Neisseria gonorrboeae, HIV, chlamydia, etc

Needle stick: Staphylococcus, HIV, HBV

Maternal-neonatal: HBV, Neisseria, etc

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 Modes of infectious disease transmission
Contact transmission
Direct contact (person-to-person): syphilis, gonorrbear, herpes
indirect contact (fomites): enterovirus infection, measles Droplet
(less than I meter): whooping cough, strep throat
 
Vehicle transmission
Airborne: influenza, tuberculoses, chickenpox
Water-borne (fecal-oral infection): cholera, diarrhea
food-borne: hepatitis, food poisoning, typhoid fever
 
Vector transmission
Biological vectors: malaria, plaque, yellow fever
Mechanical vectors: E. coli diarrhea, salmonellosis
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Antibiotic susceptibility test

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 Outline

 Antimicrobial agent
 Modes of antimicrobial actions on bacteria
 Mechanisms of antimicrobial resistance of bacteria
 Antimicrobial susceptibility testing

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 Antimicrobials

 A general term for drugs, chemicals, or other

substances that either kill or inhibit the growth of
microbes.
 Among the antimicrobial agents are antibacterial
drugs, antiviral agents, antifungal agents, and anti-
parasitic drugs.

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 Antibiotics
 Are low-molecular weight substances that are produced as
secondary metabolites by certain groups of microbes
 Antibiotics may have

– a cidal (killing) effect or

– a static (inhibitory) effect on a range of microbes.
 The range of microorganisms that are affected by a certain
antibiotic is expressed as its spectrum of action.
 broad spectrum Antibiotics: kill or inhibit a wide range of
Gram-positive and Gram negative bacteria
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 …
 Narrow spectrum Antibiotics: effective mainly
against Gram-positive or Gram-negative bacteria
 Limited spectrum Antibiotics: effective against a
single organism or disease

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 Mechanism of action of Antimicrobials

Cell wall synthesis inhibitors

 Cell wall synthesis inhibitors generally inhibit
some step in the synthesis of bacterial
peptidoglycan.
– Beta lactam antibiotics. Penicillium and
Cephalosporium
– Semi synthetic -Amoxycillin and Ampicillin have
spectra against Gram-negatives 17
 …
Cell membrane inhibitors
 These antibiotics disorganize the structure or inhibit
the function of bacterial membranes.
 The integrity of the cytoplasmic and outer
membranes is vital to bacteria, and compounds that
disorganize the membranes rapidly kill the cells. Eg.
polymyxin,  produced by Bacillus polymyxis
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Protein synthesis inhibitors
 Many therapeutically useful antibiotics owe their
action to inhibition of some step in the complex
process of protein synthesis.
 The most important antibiotics with this mode of
action are the tetracyclines, chloramphenicol, the
macrolides (e.g. erythromycin) and the
aminoglycosides (e.g. streptomycin). 19
 …
Drugs which act on Nucleic Acids
 Some antibiotics and chemotherapeutic agents affect
the synthesis of DNA or RNA, or can bind to DNA or
RNA so that their messages cannot be read.
 Two nucleic acid synthesis inhibitors which have
selective activity against prokaryotes and some
medical utility are the quinolones and rifamycins.

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Competitive Inhibitors
 Many of the synthetic chemotherapeutic agents are
competitive inhibitors of essential metabolites or
growth factors that are needed in bacterial
metabolism. 
Eg. Sulfonamides

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Antimicrobial Modes of action

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…

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 Antimicrobial Resistance

 Bacteria become resistant to antimicrobial agents by

a number of mechanisms:

1. Production of enzymes which inactivate or

modify antibiotics.

2. Changes in the bacterial cell membrane,

preventing the up take of antimicrobial agent
3. Modification of the target so that it no longer24
 …

4. Development of metabolic pathways by bacteria

which enables the site if antimicrobial action to be
by passed.
5. Increasing the production of a certain bacterial
enzyme

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Resistance • Drug resistance due to gene

• Genetic mechanism of drug transfer
resistance
• It can be due to
– Mutation
– Gene Transfer – Transformation

• Mutational drug resistance: – Conjugation

• It is of 2 types
– Transduction
1. Step wise mutation
2. One-Step mutation

• Clinical significance
– Mutational resistance is of
great importance in
Tuberculosis
 Antibiotic susceptibility testing

 Susceptibility testing is done using the following methods

– Diffusion methods: Disc diffusion-Kirby-Bauer

method

– Dilution methods
a) Agar dilution
b) Broth dilution
 Kirby–Bauer Disc Diffusion Method
o Uses small discs impregnated with antibiotics
o These discs are placed on the surface of the inoculated
Mueller Hinton agar plate, and incubated at 37oC for 24
hrs
o After incubation, plates are observed for the zone of
inhibition
o The diameter of zone of inhibition is measured using a
scale and compared with Kirby-Bauer chart
Mueller Hinton Agar Plate Swabbing
Disc Placement
 AST plate with Measurement of zone of inhibition
zone of inhibition
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• INTERPRETATION 
– Place the metric ruler across the zone of inhibition, at the widest
diameter, and measure from one edge of the zone to the other edge

– Holding the plate up to the light might help

– Use millimeter measurements. The disc diameter will actually be part of

that number

– If there is NO zone at all, report it as 0---even though the disc itself is

around 7 mm

– Zone diameter is reported in millimeters, looked up on the chart, and

result reported as sensitive, resistant, or intermediate.
 Minimum Inhibitory Concentration (MIC)

• MIC is the least concentration of antimicrobial that will

inhibit the growth of an organism after overnight incubation