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Original Author(s): Charlotte Smith
Last updated: 7th August 2020
Revisions: 9

Original Author(s): Charlotte Smith
Last updated: 7th August 2020
Revisions: 9

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Pathogens are ‘disease causing micro-organisms’. They are categorised into four broad groups, namely bacteria, viruses, fungi and parasites.

Understanding pathogens allows us to understand how they cause disease, and also helps us understand how antimicrobial agents work to prevent and treat infections caused by them.

In this article we will look at the different pathogens, how they can be classified and consider some examples of how they cause disease.

Bacteria

Bacteria are prokaryotic micro-organisms and along with viruses, account for the majority of infectious diseases in humans.

Classification

Shape

Bacteria can be classified simply by their shape. The key groups are as follows:

  • Bacilli: Also known as rods, these are long and thin.
  • Cocci: These spherical micro-organisms are found grouped together, as staphylococci (clusters), streptococci (lines) or diplococci (paired).
  • Spirilla: Spiral-shaped bacteria, although these are less common.
  • Vibrios: Flagellated (tailed) organisms, a notable example of which is Vibrio cholerae, the causative organism of cholera.
  • Spirochaete: These are tightly coiled. An example of is Treponema pallidum, the causative organism of syphilis.

Gram-Staining

The second way of classifying bacteria is according to Gram-staining. The stain is named after a microbiologist Hans Christian Gram, and has nothing to do with the measure of mass (g).

Gram-staining separates bacteria into Gram-positive and Gram-negative organisms, depending on the thickness of peptidoglycan present in the cell wall; Gram-positive bacteria have a thick layer of peptidoglycan, whereas Gram-negative have a thin layer.

Not all bacteria can be gram-stained – Mycobacterium tuberculosis is the causative organism of tuberculosis and is considered gram-indeterminate.

Figure 1 – Structural difference between gram positive and gram negative bacteria

Gram-Staining Technique

By understanding the technique used during Gram-staining, it can help you to remember which colours represent gram-positive and gram-negative organisms respectively.

  • Initially, positively charged crystal violet is added to the cells, which binds to negatively charged cell components.
  • Iodine is then added, which forms large molecular complexes with crystal violet. This stains the cell blue/purple.
  • A decolouriser such as acetone or methanol is then added to attempt to remove these large complexes from the cell. If the cell wall has a thin layer of peptidoglycan, these complexes pass out through the cell wall, removing the blue colouration.
  • The cells are then stained red with safranin.

Gram-positive organisms have a thick cell wall of peptidoglycan and so retain the crystal violet stain when washed with acetone/methanol. When safranin is added, it is retained but obscured by the crystal violet. Therefore these cells stain purple.

In contrast, gram-negative organisms have an outer lipopolysaccharide layer. When acetone is added these lipids dissolve, exposing the relatively thin peptidoglycan membrane. Crystal violent/iodine complexes are able to exit which decolourises the cell. Therefore when the red counterstain is added, gram-negative bacteria stain red.

Figure 2 – Gram positive (left) and gram negative bacteria (right)

Aerobic vs. Anaerobic

The final way of classifying bacteria is into aerobic and anaerobic, depending on their ability to survive with or without oxygen.

  • Aerobic bacteria can survive in the presence of oxygen, and obligate aerobes absolutely require oxygen to survive.
  • Anaerobic bacteria can survive without oxygen, and obligate anaerobes can only survive in an environment without oxygen.

Clinical Relevance – Common Pathogenic Bacteria

The classification of bacteria is important as it helps to diagnose bacterial diseases from swabs or samples taken from the infection site, and also guides the use of the correct class of antibiotics.

The table below classifies some common bacteria according to their Gram status and their shape.

  Gram-positive Gram-negative
­Cocci Staphylococcus aureus

Coagulase-negative staphylococcus

Beta-haemolytic streptococci

Streptococcus pneumoniae

Enterococcus faecalis

Neisseria meningitidis

Neisseria gonorrhoeae

Moraxella catarrhalis

 

Bacilli Listeria monocytogenes

Bacillis anthracis

Bacillus cereus

Escherichia coli

Klebsiella pneumoniae

Salmonella typhi

Pseudomonas aeruginosa

Haemophilus influenzae

Viruses

When considering viruses, it is key to note that they are unable to self-replicate, and need to hijack the replication abilities of their host in order to multiply.

Viral Structure

Viruses are extremely small and can only be visualised with an electron microscope. In general terms, viral particles consist of a nucleic acid core, either DNA or RNA, which is either single or double stranded.

The RNA can be either ‘positive sense’ or ‘negative sense’ depending on the polarity of the nucleic acid. Positive sense (5′-3′) RNA is directly translatable into viral proteins, while negative sense (3′ to 5′) is not.

The virus is covered by a protein coat known as the “capsid”. Some viruses also have an outer envelope. 

Figure 3 – Schematic diagram of viral structure

The cell capsid, or outer envelope if present, has glycoproteins attached to it. These bind to appropriate receptors on certain host cells, for example, glycoprotein 120 on the HIV virus binds to CD4 receptors on host T cells. This allows the virus to replicate and establish a viral infection.

Examples of common viruses, classified by structure, are below:

DNA

RNA

Enveloped

Non-enveloped

Enveloped

Non-enveloped

Hepatitis B

Human Papillomavirus HIV Norovirus
Herpes Simplex Adenovirus

Influenza

Hepatitis A

Varicella Zoster

Hepatitis C

Smallpox SARS-COV-2 (COVID)

Viral Replication

 We will now consider the process of viral replication:

  1. The virus is adsorbed onto the host cell membrane.
  2. Through the process of pinocytosis, the virus enters the cell in a vacuole.
  3. Uncoating occurs, where the outer protein coat is stripped to expose the genomic material.
  4. If an RNA virus, mRNA is generated directly. If a DNA virus or a negative sense RNA virus, transcription occurs to create mRNA.
  5. Viral mRNA hijacks host machinery to generate viral proteins. Viral nucleic acid is generated to facilitate further replication.
  6. The virion is assembled, which is an immature, inactive version of the virus. This contains the newly synthesised viral proteins and viral genomic material.
  7. The virion exits to infected another host cell, and the cycle repeats.

Further information on viral replication and infection can be found here.

Figure 4 – Viral replication

Fungi

Fungi can be sub-divided into yeasts, which are single-celled, and moulds, which are multicellular.

Examples of yeasts include Candida albicans, which causes thrush infections, and Pneumocystis jirovecii, which is a cause of pneumonia in immunocompromised individuals.

Examples of moulds include the Aspergillus species, which can cause respiratory infections in susceptible individuals.

Parasites

Parasites are less clinically relevant in the UK, but parasitic infections do sometimes occur and are an important cause of infection worldwide.

Parasites can be subdivided into Protozoa, which are single-celled, and Helminths, which are worms.

Protozoa include Giardia lamblia, which causes giardiasis, characterised by diarrhoea following foreign travel.

Examples of Helminths include roundworms and tapeworms, both of which can live in the gut and cause symptoms such as nausea and diarrhoea.