The History of Antibiotic Discovery Methods: There is a Pressing Need for Novel Platforms of Antibiotic Discovery.
Antibiotic Resistance: One of the Biggest Threats to Global Health?
What are Antibiotics?
WHO: “antibiotics are a type of medicine used to prevent and treat bacterial infections.”
What are the implications of Antibiotic Resistance?
ØEmergence of “super-bugs” or ultra-resistant bacteria which are much more difficult to treat
•Well known examples include MRSA, MSSA, E.coli, C.Difficile
ØIncreased costs to healthcare due to prolonged hospital stays and more intensive care required
•Estimated to cost the NHS around £180 million per year
ØIncreased death and mortality rates globally
•Estimated that at least 700,000 deaths per year worldwide from AMR. (NICE)
ØSurge to discover new types of antibiotics or explore alternatives to antibiotics
•New strategies include Bacteriophage therapy, bacteriocins, predatory bacteria etc.
How Does Antibiotic Resistance Occur?
* A population of microbial cells with some resistant bacterial cells
* Exposure to antibiotics kills all bacterial cells that do not confer antibiotic resistance
* The resistant bacterial population have preferred conditions and are able to grow and multiply
* Resistant bacterial cells are able to pass on this favourable gene to other bacterial cells
How is Antibiotic Resistance Transferred to other Bacteria?
There are two principal routes of antibiotic resistance transfer called Horizontal and Vertical Gene Transfer
Horizontal Gene Transfer - antibiotic resistance genes transferred from an organism that is not its parent and is typically a member of a different species
1. Conjugation: Exchange of genetic material (plasmid) from one bacteria to another
2. Transduction: Exchange of genetic material via a bacteriophage
3. Transformation: Uptake of genetic material directly from the bacterial cell’s environment
Vertical Gene Transfer - antibiotic resistance genes transferred down generations i.e. from parents to offspring
1. Random Mutation: Mutation of the bacterial cells genetic information can confer antibiotic resistance
Mechanisms of Action: Antibiotics
There are five principal antibiotic mechanisms of action to kill bacterial cells
-Inhibition of the Structure & Function of Cell Membrane
-Inhibition of Cell Wall Formation & Synthesis
-Inhibition of Nucleic Acid Synthesis & Transcription
-Inhibition of Protein Synthesis & Translation
-Inhibition of Metabolic Pathways