Antimicrobial alternatives Flashcards
What are the current antibacterial alternatives?
Bacteriocins Phage therapy RNA silencing Natural remedies Probiotics Photodynamic therapy
Why are alternatives being developed?
Due to increase in antibiotic resistance. The Golden Age of antibiotic discovery led to the production of antibiotics we use till this day. However, strains from many pathogens show resistance to most of these therapies so new methods have to be discovered.
We are at a void of discovery
What does PDT entail?
The use of wavelengths of light to activate photosensitizer molecules and produce ROS.
These are toxic to bacteria.
How do ROS kill bacteria?
Interfere with many processes like :
cell membrane production
DNA replication
What are the advantages of PDT?
Broadly specific - kills all bacteria whether antibiotic sensitive or not
Does not create selection pressure
Many targets means the development of resistance is negligible
Localised short term treatment due to short lifespan of ROS
Which conditions does ROS treat in present day?
Many conditions in the oral cavity - caries and peridontitis
MRSA in rats
What are bacteriocins?
They are antimicrobial peptides produced by bacteria to inhibit neighbouring bacteria.
Produced in the ribosome, these allow the bacteria to outcompete with others for nutrients.
Uses of bacteriocins
Nisin E234 - food preservative
Biofilm eradication - clinical trial
How do bacteriocins kill bacteria?
Form pores on their CSM - reduce the membrane potential and leads to leakage of cell contents
Endonuclease activity - degrade chromosomes
Cell wall - sequesters lipid II (important precursor for peptidoglycan) or destroys proteins in the cell wall/in cell
How can we use bacteriocins therapeutically?
Genetic manipulation of the 11 genes on operons required for functionality can produce novel variants with extended activity and different specificities.
What are probiotics?
Probiotics use bacteria from commensal populations in our body to confer health benefits.
How can bacteria from commensal populations lead to pathogen death?
Outcompete pathogens for nutrients/ space
Synthesise bacteriocins
Prevent adhesion to host cells
Mechanism of probiotic therapy
Foecal transplantation has been 90% effective
What is phage therapy?
The use of bacteriophages to treat bacterial infections. Viruses invade bacteria and cause cell lysis.
Advantages of phage therapy
Narrow spectrum of activity - only affects one bacterial species/strain
Resistance can occur naturally but the phage can co-evolve to re-infect the phage-resistant bacteria
Is phage therpay used therapeutically?
In Soviet Union yes - cheaper than antibiotics, Intestiphage and Prophage used
In UK and US - clinical trials for Intralytix used to heal wounds. Used comercially in food preservation.
Natural remedies combating bacterial infections
Honey - low pH, H202, high glucose
Metal nanoparticles - wound healing
Tea tree oil - skin infections, deodorant and shampoos
What is RNAi?
RNA interferance is a natural mechanism by which cells silence the expression of certain genes.
What is the process of RNAi?
Two important RNA molecules are synthesised in our cells
siRNA (small interfering RNA)
microRNA
These work by binding to complementary strands on mRNA being translated and causes them to be cleaved off, essentially silencing their genes.
Where is siRNA and microRNA made?
siRNA - cleaved from bigger RNA molecules or injected experimentally
microRNA - in the nucleus
How do siRNA and microRNA become activated?
siRNA and microRNA bind to proteins in the cytoplasm and are cleaved.
They then tranfer to other proteins called Argonauts and form the RNA Induced Silencing Complex.
These RISC complexes then bind to complementary strands on the translated mRNA and causes their gene silencing.
Is microRNA or siRNA more specific?
siRNA binds to the full complementary chain and so is more specific. microRNA only binds via a complementary portion called SEED and so is more broadly specific.
Future of RNA silencing therapy
Since we can observe that certain RNA molecules are directed to produce gene silencing, we could manipulate this feature and inject siRNA experimentally to silence the genes coding for resistance.
Hurdles of RNA therapy
Concentration of the oligonucleoside needed is unknown - must be high enough to sequester all target mRNA
Mechanism of resistance and genetic basis not known - need to know genes involved
Need to develop nucleotide carriers to protect oligonucleotide
Future of antibiotics
Lots of research and development
Cost is high however
Due to this and development of likely resistance, drug companies are not interested
How to make antibiotic market more attractive
Incentivise it
