Extracellular DNA is a structural component of bacterial biofilms and serves many essential purposes. eDNA provides structural support by binding cells together and allowing attachment of the biofilm to surfaces. eDNA is an indispensable part of an effective bacterial biofilm.
eDNA provides a physical barrier between the bacteria and antibacterial agents and the immune system, making antibiotics much less effective by binding them.
eDNA can interact with other molecules to open lines of communication between bacterial cells in a process called quorum sensing. Think of quorum sensing as a fancy word for bacteria chatting to each other about what to do next.
How do My Vagina treatments break down eDNA?
Minerals, while not as prominent as organic compounds in biofilms, play supportive roles in structure and function. Minerals have a context-dependent impact, which varies across bacterial species and environmental conditions.
Calcium and magnesium, for example, stabilise the biofilm matrix via cross-linking organic components like eDNA. Iron and other trace minerals are important for bacterial metabolism and gene regulation, which indirectly influences biofilm formation.
My Vagina’s vaginal pessary treatments usually contain a biofilm component, typically cinnamon extract or EDTA. EDTA draws minerals from the biofilm, causing collapse.
Horizontal gene transfer: a video game where you collect berries and weapons
eDNA is taken up by other bacteria via a process called transformation, which allows horizontal gene transfer. This is the process whereby one microbe can pass its antibiotic-resistance genes to an utterly unrelated microbe without even touching it, on the spot.
Horizontal gene transfer is more about collecting berries for healing, or weapons for fighting, in a video game, rather than spending decades breeding specific traits. This is why antibiotic resistance is such a looming threat – it’s spreading at an incredible rate due to horizontal gene transfer.
In humans, we think of DNA being passed between generations (nose from mum, hair from dad, etc.), but this does not happen for microbes. They can be standing around doing nothing, and an eDNA particle comes near them, and they pluck the antibiotic resistance gene out of it and say, why thank you very much. Then they have that gene.
In a bacterial biofilm, this is a problem for the host (you), but great for the bacteria being protected by the biofilm.
Where does eDNA come from?
Bacteria like Gardnerella vaginalis, one of the main players in chronic bacterial vaginosis (BV), release their own eDNA. A group of bacteria are the suicide bacteria, and they self-destruct and release their DNA into the vaginal environment for use by their friends.
Additionally, G. vaginalis and other bacteria can cram DNA into smaller packages and then release them, like a glitter bomb, except not fun. Bacteria can also have special appendages to secrete DNA.
Is eDNA ever good for us?
Our human bodies use eDNA all the time for activities like wound healing and immune signalling. eDNA is essential. However, in infections, bacteria eDNA makes biofilms strong, infections persistent, and treatment-resistant.
What is eDNA made of?
eDNA is made of the same materials as intracellular DNA (iDNA), which means it’s a polymer made of nucleotides (deoxyribose sugar, phosphate groups, and nitrogenous bases).
eDNA is exactly the same as iDNA, a double or, less commonly, single-stranded helix, with polarity: each end is different.
Where does eDNA come from?
All eDNA was iDNA, but became extracellular – outside the cell it came from – due to one of several mechanisms.
We learnt earlier that eDNA is deliberately sprinkled around by bacteria to build biofilms, but eDNA is also released after a ruptured cells (or a bacterial cell) due to normal cell death (lysis).
Importantly, dead cells naturally release their DNA into the environment. Our cells are constantly dying and replacing themselves, so normal shedding releases eDNA into the area. When there is inflammation, more cell death and shedding occurs, providing more eDNA.
Can we break down eDNA?
eDNA is a target for many new treatments for biofilm-related infections. Disrupting eDNA weakens the biofilm, allowing treatment to be more effective.
eDNA breaks down in the presence of enzymes and some environmental factors. DNases are enzymes that break down DNA by splitting the bonds in the backbone of the DNA. There are several forms of DNase: DNase I, DNase II, and microbial DNases.
Understanding DNase I
DNase I is found in blood and saliva and breaks DNA into smaller fragments. As a medical therapy, for example, doctors use DNase I in people with cystic fibrosis to break down the DNA in mucous.
Understanding DNase II
DNase II is in lysosomes, which are special little packages of enzymes inside cells that have a few key jobs. Lysosomes have the stuff to break down polymers (remember, DNA is a polymer!).
But, lysosomes participate in critical cell housekeeping processes like repairing the cell membrane, energy use, programmed cell death (apoptosis), cell signalling, and secretion.
DNase II kicks off at an acidic pH, which is essential in the vaginal ecosystem. DNase II will break down the eDNA of dead cells or in biofilms in an acidic environment. In BV, the environment is less acidic, so DNase II is not as active.
Understanding microbial DNases
Many bacteria and fungi produce DNases to degrade eDNA in biofilms or to outcompete other microbes in their environment.
When someone steals your dance partner (free radicals)
Free radicals, a particularly cool name for reactive oxygen species (ROS), are always around. Think of free radicals as the dancer who comes and steals your dance partner, leaving you alone, but isn’t able to dance correctly, leaving nobody dancing.
ROS are unstable molecules that contain oxygen and easily interact with other molecules in a cell. A build-up of ROS inside a cell (many stolen but useless dance partners) can damage DNA and other cell functions and can ultimately cause cell death.
ROS are normal and healthy as long as they don’t get too numerous, which is what is known as oxidative stress. You’ve no doubt heard of antioxidants. Antioxidants swan onto the dance floor and swoop the free radical off the dancefloor, taking them to the bathroom for a chat. Think vitamin C.
ROS damage DNA by breaking down the sugar-phosphate backbone of the DNA structure, changing or removing the nitrogenous base, and causing DNA strand breaks. During inflammation, oxidative stress, or in certain microbial interactions, ROS are generated.
If you have a vaginal infection, your vaginal cells are inflamed to a greater or lesser degree, and ROS are being produced. ROS damage eDNA. But, remember, this isn’t desirable; it’s just what damages DNA, including our healthy DNA.
Environmental factors that degrade eDNA
UV light
Ultraviolet light leads to DNA strand breaks, which is why tanning beds have been banned globally; tanning causes DNA breakdown and skin cancers. UV light damages the DNA in cells – including the skin.
High or low pH and heat
Extremes of pH – very acidic or very alkaline – can break the bonds of DNA, degrading it. High temperatures degrade DNA.
References1–4
- 1.Peterson BW, van der Mei HC, Sjollema J, Busscher HJ, Sharma PK. A Distinguishable Role of eDNA in the Viscoelastic Relaxation of Biofilms. Chapman M, Hultgren SJ, eds. mBio. Published online November 2013. doi:10.1128/mbio.00497-13
- 2.Campoccia D, Montanaro L, Arciola CR. Extracellular DNA (eDNA). A Major Ubiquitous Element of the Bacterial Biofilm Architecture. IJMS. Published online August 23, 2021:9100. doi:10.3390/ijms22169100
- 3.Okshevsky M, Meyer RL. The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Critical Reviews in Microbiology. Published online December 4, 2013:341-352. doi:10.3109/1040841x.2013.841639
- 4.Secchi E, Savorana G, Vitale A, Eberl L, Stocker R, Rusconi R. The structural role of bacterial eDNA in the formation of biofilm streamers. Proc Natl Acad Sci USA. Published online March 15, 2022. doi:10.1073/pnas.2113723119
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