An Introduction to Infection

1. Steps of Infection
2. Commensals
3. Virulence and Toxins
4. Post-infection
5. Quiz

• Infection is the invasion of a host’s tissues by disease-causing microorganisms
• A patient may be infected by vertical (in pregnancy) or horizontal (from the environment) transmission
• A full history supported by investigation and examination allows identification of an infected patient

• Direct contact transmission occurs when there is physical contact between an infected person and a susceptible person. For example- Most sexually transmitted infections (STIs) are transmitted in this way. 
• Indirect contact transmission occurs when there is no direct human-to-human contact, but the susceptible patient comes into contact with a contaminated surface or object (a fomite). Transmission can also occur via vectors, which are living organisms that carry and transmit infection, such as mosquitoes, flies, mites, fleas and ticks. In indirect contact transmission, the susceptible person comes into contact with a contaminated object (fomite), such as a door handle that has been sneezed on, or with a vector, such as an Anopheles mosquito that has fed on an infected human.

2. Inhalation - involves the entry of infective microorganisms through the respiratory tract. This can be broadly split into airborne and droplet transmission. In airborne transmission, very small particles generated by coughing, sneezing or breathing can remain suspended in the air for prolonged periods. Droplet spread however has a much larger particle which when coughed or sneezed out will fly for a short distance before dropping to the floor or a surface which it may then contaminate.

3. Ingestion - involves the entry of infective organisms through the gastrointestinal system. It mainly consists of faeco-oral transmission which is usually when food or water contaminated with faeces is ingested. Although it is rare for individuals to knowingly directly ingest faeces, this may happen with microscopic amounts of faeces in cases of poor hand hygiene.  A few examples of how this happens would be: drinking water contaminated with sewage, eating shellfish/raw fruit and vegetables that have been harvested or washed in contaminated water, sexual activity, or poorly managed/chlorinated swimming pools.
 
 
 

Image: High quality swimming pool management - anyone for a swim?

2. Adherence

Simply put adherence is the binding of a pathogen to a host cell. This is done using an adhesion protein, or ligand, on the bacterial cell wall or viral capsule surface, which then binds to a receptor (a carbohydrate structure bound to the lipid membrane) on a host cell.
Fimbriae are also believed to be involved in attaching some bacteria to a solid surface or another cell (there is a structural difference between pili and fimbriae but the terms are mostly used interchangeably) - this is one example of a virulence factor, a specific adaptation of a pathogen (organism capable of infection) that allows it to better infect cells, replicate and survive.

3. Invasion

Image: Mycobacterium tuberculosis is a pathogenic mycobacterium and is the causative agent of Tuberculosis.

Non-Phagocytic cell invasion

Bacteria that invade non-phagocytic cells work slightly differently by something called the zipper method. Using Yersinia pseudotuberculosis as an example, the bacterium will bind to a receptor that is involved in binding to other cells, which tricks the cell into forming a cell junction with it. The bacterium is relatively small compared to the host cell so the host cell tries to spread over the adhesive surface of the bacterium, endocytosing it (receptor-mediated endocytosis).

The other way bacteria infect nonphagocytic cells is by the trigger method. In short the bacterium injects molecules into the host cell which activates the Rho family of GTPases, that changes the shape of the actin cytoskeleton so it can fold over the bacterium and invaginate it.

4. Multiplication

Multiplication of bacteria is via the mechanism of binary fission. The process starts with replication of the main strand of circular DNA of the bacteria into two copies. The next step is the replication of any plasmids; small circular strands of DNA which contain any ‘luxury genes’ ie those not crucial in the basic functioning of the bacteria. Multiple copies of these plasmids may be made. The final step is when the main strand copies move to opposite poles of the cell, the bacteria pinches in the middle and finally divides into two.
In viruses, the host cell's multiplication machinery is taken over and used as a "factory" for further viruses to be produced based on the RNA/DNA of the initial virus which infected the cell. The copies are then released from the cell to infect further cells.

5. Dissemination

Dissemination involves the spreading of the bacteria/ viral load from one part of the body to another. For example, infection with TB, this is from the lungs to a secondary site (normally another organ) through the blood and lymphatics. Viruses released from body cells will circulate around the body looking for cell-surface receptors that they can bind to, in order to enter the target cell and begin multiplication again.

The microbiome is the community of microorganisms, their genes and their local chemical environment at a body site. Its composition differs between the bowel, skin, mouth and vagina because each site supplies different nutrients, oxygen tensions, surfaces and host secretions. A stable microbiome is not simply passive. Gut organisms ferment otherwise indigestible carbohydrate to short-chain fatty acids, including butyrate, which can fuel colonocytes and support the epithelial barrier. Microbial products also help immune tissues learn to tolerate ordinary residents while remaining able to respond to invasion. Some organisms contribute to vitamin and bile-acid metabolism, although the importance of any one function varies by site and community.

Colonisation resistance is the protection that established organisms provide against an incoming pathogen. They occupy attachment sites, consume limiting nutrients, alter local pH and oxygen conditions, and may release bacteriocins or other inhibitory products. They also support mucus, epithelial junctions and a measured basal immune response. A pathogen must overcome several of these barriers before it can multiply successfully.

This protection is ecological rather than absolute. Broad-spectrum antibiotics can remove susceptible members of the community and leave nutrients or niches available to resistant organisms, helping explain the opportunistic expansion of Clostridioides difficile described below. Normal residents can also cause disease if they enter a normally sterile compartment or host defences fail. For the cell structures, oxygen classifications, spores and growth phases that determine how bacterial populations survive and expand, see Bacterial Structure, Classification and Growth.

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