Tuesday, August 1, 2017

Commensal Flora and Pathogenesis

Know the role of commensal flora in health and disease.

Commensal flora is a term that refers to bacteria that normally live in and on your body, usually on body surfaces such as the skin and GI tract. They are different to transient flora, which are only present temporarily (days to months). Most commensal flora are harmless and even beneficial, but in some cases they can cause opportunistic infections. Commensal flora can prevent the overgrowth of pathogens, produce vitamin K and B12, aid in food absorption, and degrade harmful compounds.

Commensal flora can be influenced by a variety of factors, such as the presence of antimicrobials, inhibitory body secretions, and interactions with other organisms.

Know specific mechanisms by which commensal flora are protective.

Commensal flora can protect us from pathogenic bacteria by competing for space and nutrients. Commensal flora can also produce bacteriocins, which damage bacteria, and can alter the environment to make it unfavourable (for example, some secrete lactic acid, which lowers the pH). Therefore, commensal flora acts alongside other aspects of innate immunity, which I have blogged about here.

Know stages of infection and modes of disease transmission.

Firstly, just a quick note on primary vs. opportunistic pathogens. Primary pathogens, such as B. anthracis and Y. pestis, are capable of causing disease in everyone. Opportunistic pathogens, such as coagulase negative staphylococci and E. coli, generally only cause disease in people with compromised defence mechanisms.

The stages of infection are as follows:
  1. Transmission of the pathogen to the host- the pathogen has to get to you before it can hurt you!
  2. Entry into the host- this can occur when natural barriers (like skin and mucous membranes) are broken, or if the pathogen can overcome them in some way. Sometimes the pathogen might attach to the skin or mucous membranes.
  3. Local multiplication and spread- Self-explanatory. Some pathogens are able to invade tissues during this stage.
  4. Systemic multiplication and spread- Like step 3, but more widespread.
  5. Exit- Some members of the pathogen leave in order to infect a new victim.
Transmission of pathogens can be direct (from organism to organism) or indirect (from object to organism). Direct transmission includes horizontal contact (e.g. kissing and other kinds of contact between people), vertical contact (mother to child), airborne (sneezing) and vector-borne (via mosquitoes etc.). Indirect transmission includes contact with contaminated objects, food and water, and dust.

Know several virulence factors associated with pathogenesis.

Virulence factors include capsules, pili, enzymes, and toxins. Some bacteria have capsules, which mediate the adherence of the bacteria to cell surfaces, as well as prevent phagocytes from adhering and digesting the bacteria. Pili are hair-like structures that help in adherence to the host cell. A variety of enzymes can also help with tasks such as tissue invasion: collagenase and hyaluronidase break down collagen and hyaluronic acid, coagulase creates a fibrin clot around bacteria to protect from phagocytes, and IgA protease degrades IgA and allows for attachment to mucous membranes. Toxins can help out too: leucocidin destroys both neutrophils and macrophages, allowing the bacteria to do its thing unhindered.

Toxins come in two flavours: exotoxins and endotoxins. Here's a little table explaining the differences:

Exotoxins Endotoxins
Produced by Gram +ve and Gram -ve Gram -ve only
Comprised of Protein Lipid A of outer membrane lipopolysaccharide
Heat stable? No Yes

Exotoxins can be converted into toxoids via treatment with formaldehyde, acid, or heat. Toxoids are non-toxic, but still antigenic. This makes them useful in the production of vaccines, such as the tetanus toxoid vaccine.

Know examples of diseases resulting from disruption of commensal flora.

C. difficile is an anaerobic Gram +ve bacillus that can cause diarrhoea in hospital patients. It is an opportunistic pathogen which usually only causes problems when our commensal flora has been disrupted by antibiotics. Candida albicans (a fungus), which causes thrush, is also an opportunistic infection that becomes problematic when antibiotics destroy your commensal flora.

Fun fact: faecal transplants have been explored as a possible treatment for C. difficile. Transplanting faeces restores the normal commensal flora population. It has a fair amount of "ick factor" associated with it though :P

Another example of a disease resulting from disruption of commensal flora is bacterial vaginosis, which is caused by Gardnerella vaginalis and other anaerobes. Gardnerella usually only becomes a problem when Lactobacilli are depleted. Lactobacilli usually protect us by producing lactic acid (which lowers the pH, making the environment unfavourable), producing antimicrobial substances, producing hydrogen peroxide, and forming a barrier to colonisation.

No comments:

Post a Comment