Pathogenicity and Virulence
Pathogenicity and Virulence
All bacteria differ in their individual ability to cause infectious process.
- It means the potential capacity of a certain microbial agent to cause an infectious process in the susceptible organism.
- Pathogenicity is the species inherited genetic feature.
- Unlike saprophytic bacteria, pathogenic microorganisms harbour pathogenicity genes that encode the vast number of virulence factors – toxin production, invasion enzyme synthesis, adhesin expression, effector protein synthesis, etc.
- Pathogenicity genes in bacteria are usually organized into special genetic clusters known as pathogenicity islands.
- Typical structure of the pathogenicity island includes several virulence-linked genes (encoding toxins, secretion system structures, capsule synthesis, etc.) as well as the genetic elements responsible for the mobility of pathogenicity island (IS-elements, integrase genes, direct repeats sequences, and others).
- In addition, the genetic sequence of pathogenicity island is quite different from the basic sequence of the microbial genome. For instance, pathogenicity islands can be distinguished from the other parts of nucleoid by (G+C) nucleotide content.
- Therefore, pathogenicity islands are the transmissible genetic structures capable of spreading among the various groups of bacteria by lateral gene transfer. The acquisition of these genes endows the bacteria with pathogenic properties.
- It signifies the degree of pathogenicity of the certain microbial strain. It is the quantitative ability of the microbial agent to cause infectious disease (phenotypic trait).
- Virulence is seen as the severity of disease manifestation that can only be measured in infected individuals
- Virulence results from the expression of pathogenicity genes with the synthesis of a great variety of virulence factors (toxins, adhesins, invasive enzymes, etc.)
- To measure the virulence levels, various units of virulence have been proposed. In general, virulence is indicated “by case fatality rate and/or by the ability of a microorganism to invade the tissues of the host”.
- One of the virulence units for measurement is Dosis letalis minima (or DLM). It corresponds to the minimal quantity of live microorganisms, which causes the death of 95% of experimental animals in a certain period of time.
- Also the absolute lethal dose – dosis certa letalis (Dcl) – can be evaluated. This dose causes the death of all 100% of the experimental animals.
- And more precise is median lethal dose or LD50 – the dose that is lethal to 50% of the infected experimental animals.
- The infectious dose (or ID) of a certain pathogenic agent indicates a definite amount of pathogenic microorganisms that is enough to produce the infectious disease in standard experimental conditions. It is expressed in units of ID50 or ID95.
- It has been found that the infectious dose varies from less than 10 bacterial cells for enterohemorrhagic E. coli to 108-1011 microbial cells for El Tor cholera vibrios.
- The potency of toxins is estimated by laboratory animal tests according to Dlm and LD50. For instance, 1 Dlm of the diphtheria toxin is equivalent to the minimal amount of toxin that after subcutaneous injection of guinea pigs kills them on the fourth day of the experiment.
- Virulence is altered under the influence of the environment and by the pressure of host defensive systems. It can be increased by the number of microbial passages through the susceptible experimental animals as well as by culturing on the special media enriched with growth factors.
- On the other hand, virulence can be diminished by a great variety of factors (passages through resistant lines of laboratory animals, treatment with antimicrobial drugs, the action of disinfectants and other chemicals, cultivation in poor media, etc.)
- More advanced methods include genetic engineering manipulations that may either increase or decrease the virulence.
Basic Virulence Factors of Bacteria
- Every case of infection comprises a great set of specific reactions between the virulent microorganism and its susceptible host.
- They include selective interaction and attachment of bacteria to host cell receptors, membranes and tissues (adhesion or adherence), replication of pathogenic agents in the place of their attachment (colonization), their ability to overcome the cellular and tissue barriers (penetration and invasion), toxin production (toxigenicity), inactivation of host immune factors (immunosuppression), inactivation of antimicrobial agents (antimicrobial resistance).
All these reactions are stimulated by the powerful virulence factors, produced by microbial cells. As a result, highly virulent bacteria in minimal doses may cause severe diseases with lethal outcome.