Biofilms Flashcards
What is a biofilm?
Biofilms are organized communities of bacteria that are adhered to a surface and are surrounded by (enmeshed in) a matrix of extracellular polymeric substances (EPS).
The EPS is a slimy, film-like substance produced by the bacteria of the biofilm, and is composed of polysaccharides, proteins and nucleic acids.
A biofilm is often composed of a single bacterial species.
However, some biofilms have been found to contain hundreds of different species of bacteria living together.
What is quorum sensing and how does it play into biofilm formation?
As a result of coordinated chemical signaling between cells (called quorum sensing), and when the benefits of forming a community outweigh the costs.
Quorum sensing uses signaling molecules, called autoinducers, which are produced by bacteria.
The bacteria also possess receptors for these signaling molecules.
When elevated numbers of bacteria are present in close proximity to each other, autoinducer concentration increases.
Once the binding of autoinducer molecules has exceeded a certain threshold, a signaling cascade is initiated that modulates gene expression and in turn, modulates bacterial physiology to encourage community development.
Explain the steps of biofilm formation.
- Free-floating, or planktonic, bacteria encounter a submerged surface and within minutes can become attached.
- They begin to produce slimy extracellular polymeric substances (EPS) and to colonize the surface.
- EPS production allows the emerging biofilm community to develop a complex, three-dimensional structure that is influenced by a variety of environmental factors. Biofilm communities can develop within hours.
- Biofilms can propagate through detachment of small or large clumps of cells, or by a type of ‘seeding dispersal’ that releases individual cells.
- Either type of detachment allows bacteria to attach to a surface or to a biofilm downstream of the original community.
List the steps of biofilm formation (no explanation).
- adherence of bacteria to a surface
- growth and production of EPS, resulting in much stronger (often irreversible) attachment
- dispersion of single cells from the biofilm
What does the term planktonic refer to?
Single bacterial cells that are growing in liquid (i.e., standard laboratory) culture, or to single bacterial cells swimming freely above a biofilm.
Planktonic bacteria can be recruited to a biofilm or may have sloughed off an existing biofilm.
Explain how the bacteria in biofilms differ from one another.
Bacteria in a biofilm behave as a group: they sense and respond to stimuli in a coordinated manner. Some biofilm structures include a network of pores that provides a primitive circulatory system. Bacteria deep inside the biofilm have a different physiology than the bacteria closer to the surface (due to different O2 and nutrient availability), and the EPS holds it all together.
Give examples of benign environmental biofilms.
Slippery coatings on rocks in streams, coatings on ship hulls, etc.
Although these biofilms do not generally cause human disease, they are responsible for significant industrial problems such as corrosion.
Give examples of pathogenic biofilms on implanted medical devices.
A variety of bacteria, both Gram-negative and Grampositive, readily form biofilms on many foreign devices implanted into human bodies. These bacteria account for significant human infection and disease.
a) urinary catheters
b) heart valve implants
c) hemodialysis equipment
d) dental implants
Give examples of pathogenic biofilms on human body surfaces.
Bodily surfaces provide an ideal environment for formation of many different types of biofilms. Many of these infections are caused by opportunistic pathogens that are also human commensals.
Often the biofilm nature of the infection results in chronic disease that is difficult to treat with antibiotics.
Examples of such infections include:
- cystic fibrosis (CF) infections in the lung, caused by Pseudomonas aeruginosa
- tuberculosis infections caused by Mycobacterium tuberculosis,
- urinary tract infections caused by Escherichia coli
- ear infections (variety of bacteria)
- tonsillitis (variety of bacteria)
- oral biofilms. These biofilms are the primary causative agents of dental caries and gingivitis, and are probably the best-studied model biofilm communities in terms of human infection
Give examples of environmental biofilms that impact human health.
- Hot water systems in hospitals contaminated with Mycobacterium avium.
- Drinking water reservoirs contaminated with Salmonella typhimurium.
- ‘Benign’ biofilms can attract, recruit, and concentrate pathogenic bacteria that might not form a biofilm on their own. This has many implications, one of which is bioterrorism. For instance, biofilms on copper tubing have been shown to attract and concentrate Bacillus anthracis (anthrax) spores.
What are biofilm properties thought to contribute to antimicrobial resistance?
- The EPS matrix. The complex EPS layer enmeshing the biofilm can significantly impede the penetration of antimicrobial agents to bacteria buried in the depths of the biofilm.
- Nutrient and O2 availability. Bacteria within a biofilm are subject to nutrient and O2 gradients, meaning bacteria closer to the surface have significantly better access to nutrients and O2 than bacteria on the interior. Consequently, bacteria in the biofilm interior, while alive, are often metabolically inactive. Antibiotics are most effective against metabolically active cells (more on this in V); thus, bacteria in the interior are protected from this type of killing.
- ‘Persister’ cells. Sometimes, the majority of a biofilm can be killed by antimicrobial therapy; however, a very small percentage of the population remains viable despite prolonged exposure to the antimicrobial or increased dosage. These persisters generally confer no heritable resistance to progeny once the selective pressure is removed; however, this characteristic allows cells in a biofilm to survive for extremely long periods of time, and likely contributes to long-term survival of bacterial species in general.
Give examples of new pharmaceutical approaches to anti-biofilm therapy.
- Interfering with EPS synthesis. For instance, coating medical devices with chemicals that hinder matrix formation
- Inhibiting adherence of biofilms to their surface substrate. For instance, identifying chemicals that bind to bacterial cell surfaces, stopping formation of biofilms before they begin, and
- Targeting autoinducers. If the bacteria can’t signal to each other, they won’t be able to form or maintain a biofilm.
Describe the skin as a host defense mechanism.
Skin is composed of epidermis (keratin), which is virtually impregnable.
Infections may result when there are breaks in the epidermis, e.g., abrasions, puncture wounds and insect bites.
The skin lacks moisture and has a high salt concentration.
Sebaceous glands secrete fatty acids and lactic acids, which decrease the pH of the skin and inhibit the growth of microorganisms.
Furthermore, genes encoding antimicrobial peptides (e.g., Dermcidin) are expressed in sweat glands, and the antimicrobial peptides are secreted into sweat and transported to the epidermal surface.
Describe the upper respiratory tract as a host defense mechanism.
The URT (which includes the nose, throat and ears) is exposed to >104 bacteria/day; that is, approximately 7 bacteria/minute!
The major barriers to microbial infection in the URT include the mucous membranes that contain mucoussecreting cells and ciliated cells, i.e., the mucociliary system.
The mucous traps the bacteria and the cilia beating sweeps them up and out of the URT.
Furthermore, this area is heavily colonized with microbiota.
This may include opportunistic pathogens e.g., Neisseria meningitidis.
This area is partly protected by antimicrobial peptides in body secretions (tongue, throat).
What are ‘persister’ cells?
Sometimes, the majority of a biofilm can be killed by antimicrobial therapy; however, a very small percentage of the population remains viable despite prolonged exposure to the antimicrobial or increased dosage.
These persisters generally confer no heritable resistance to progeny once the selective pressure is removed; however, this characteristic allows cells in a biofilm to survive for extremely long periods of time, and likely contributes to long-term survival of bacterial species in general.