Medical Microbiology - Lecture Notes - TIU

Heshu J. Ahmed/Assist. Lecturer_____________________________________________Pathogenesis of bacterial infections – 2nd Stage /2nd Semester

Heshu.jalal@tiu.edu.iq

https://tiu.edu.iq/

2020 - 2021

TIU - Faculty of ScienceMedical Analysis Department

Medical Microbiology

Introduction

A pathogen is a microorganism that is able to cause disease in a

plant, animal or insect.

Pathogenicity is the ability to produce disease in a host

organism.

Microbes express their pathogenicity by means of their

virulence, a term which refers to the degree of pathogenicity of the

microbe.

Determinants of virulence of a pathogen are any of its genetic

or biochemical or structural features that enable it to produce

disease in a host.

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 dependson:

the virulence of the pathogen and

the relative degree of resistance or susceptibility of the host,

mainly due to the effectiveness of the host defensemechanisms.

Introduction

Animals and microbes

Normal flora (beneficial or ignored): GI track, skin, upper respiratory track

Virulent bacteria (actively cause disease): pathogenic islands

Opportunistic bacteria (when host with underline problem): Pseudomonas aeruginosa: cystic fibrosis/burn

TB, Kaposi’s sarcoma (herpesvirus): AIDS

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 bypass or overcome host defense

mechanisms.

Mechanisms of Bacterial Pathogenicity

2. Toxogenesis: ability to produce toxins.

Bacteria may produce two types of toxins:

i. exotoxins and

ii. endotoxins.

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).

Endotoxins may be released from growing bacterial cells

and cells that are lysed as a result of effective host defense

(e.g. lysozyme) or the activities of certain antibiotics (e.g.

penicillins and cephalosporins).

Hence, bacterial toxins, both soluble and cell-associated,

may be transported by blood and lymph and cause cytotoxic

effects at tissue sites

Some bacterial toxins may also act at the site ofcolonization

and play a role in invasion.

Mechanisms of Bacterial Pathogenicity

Tissue destruction: flesh-eatingbacteria:

Clostridium perfrigens

Immunopathogenesis

Excess immune responses

Autoimmunity

Stages of Bacterial pathogenesis

Infection/entry

Virulence factors

Pathogenesis

Escape of immune surveillance

Infection/entry

Ingestion (fecal-oral)

Inhalation (respiratory)

Trauma (e.g burn)

Arthropod bite (zoonoses:

mosquito, flea, tick,

Tsetse fly)

Sexual transmission

Iatrogenic (needle stick,

blood transfusion)

Maternal-neonatal

Bacteria, virus, fungi

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

Inhalation: Mycobacterium, Mycoplasma, Chlamydia etc..

Trauma: Clostridium tetani

Arthropod bite: Yersinia pestis.

Sexual transmission: Neisseria gonorrhoeae, HIV, chlamydia, etc

Needle stick: Staphylococcus, HIV, HBV

Maternal-neonatal: HIV, HBV, Neisseria, etc.

Modes of infectious disease transmission

Contact transmissionDirect contact (person-to-person): syphilis, gonorrhear, herpesIndirect contact (fomites): enterovirus infection, measles

Droplet (less than 1 meter): whooping cough, strep throat

Vehicle transmissionAirborne: influenza, tuberculoses, chickenpoxWater-borne (fecal-oral infection): cholera, diarrhea

Food-borne: hepatitis, food poisoning, typhoid fever

Vector transmissionBiological vectors: malaria, plaque, yellow fever

Mechanical vectors: E. coli diarrhea, salmonellosis

Extracellular versus Intracellular Parasitism

Extracellular parasites

destroyed when phagocytosed.

damaging tissues as they remain outsidecells.

inducing the production of opsonizing antibodies, they

usually produce acute diseases of relatively short duration.

Intracellular parasites

can multiply within phagocytes.

frequently cause chronic disease.

Virulence factors

Factors enhancing the ability of bacteria to cause disease

Example: Pseudomonas aeruginosa

Adhesins: attachment

Alginate production: mucoid layer

Exotoxin A: inhibits host proteinsynthesis

Exoenzyme S: interferes with phagocytic killing

Elastolytic activity: degrades elastin

Phospholipase C: damages tissue

Pyocyanin: damages tissue by ROS

Antibiotic resistance: complicates therapy

Bacterial Toxins

Many different types of toxins

Exotoxins

Endotoxins

Toxins are are not required forgrowth

Genes for toxins are usually on plasmids

EXOTOXINS.

Produced inside some bacteria as part of theirgrowth and metabolism and released into thesurrounding medium

Are proteins, and many are enzymes

Most bacteria that produce exotoxins are gram-positive

The genes for most exotoxins are carried on bacterial plasmids or phages.

Neurotoxin.

Target the nervous system, and can interfere with normal nerve impulse transmission, e.g. C. tetani, C.botulinum.

ENTEROTOXINS. Affect cells lining the gastrointestinal

tract.

E.g. V. cholerae, C. difficile.

Superantigens

Secreted proteins

(exotoxins) that exhibit

highly potent lymphocyte-

transforming (mitogenic)

activity directed towardsT

lymphocytes.

Known and suspected association of superantigens with

animal diseases

Autoimmune diseases

Lyme disease

Multiple sclerosis

Acute diseases

Food poisoning:

Staph infections

Streptococal

2. Endotoxins: heat stable

Bacterial Endotoxins

Endotoxins Toxin is not internalized

Toxin is located on outside of microorganisms (Part of the outer portion of the cell wall ofbacteria)

LPS of gram – bacteria

Lipoteichoic acid or gram + bacteria

Only toxic at high levels

Liposaccharide

Exert their effects when the gram negative bacteria dies and their cell wall undergo lysis, thus liberating the endotoxin(e.g use of antibiotics)

All endotoxins produce the same signs and symptoms

Endotoxins can also induce miscarriage.

Fever, Disseminated intravascular coagulation, Septic shock and death

Thank you