CSIM 1.43 Development of Antibiotic Resistance Flashcards
What is the definition of antibiotic?
Any substance produced by a microorganism which inhibits growth of other microorganisms
Which type of bacteria is more susceptible to beta-lactam containing antibiotics?
Gram-positive bacteria
What does penicillin bind to? What is the normal function of this
Penicillin binding protein
• Normally cross links the chains of the cell wall forming peptidoglycan
• Penicillin binds to the active site of this protein
• Therefore the cross-linking stops forming
• The cell wall size is now fixed, but the bacterium still tries to grow
• The osmotic and cell contents pressure exceeds what the cell wall is capable of containing and the cell membrane herneates from the cell wall
• The cell wall is shed, forming a spheroplast
• There is now no protection from osmotic pressure, so the cell eventually bursts - death by osmosis
IMG 113
In what ways can antibiotic resistance come about?
- Bacterium can chemically modify the antibiotic
- The bacterium can physically remove the antibiotic from the cell (in antibiotics which require entry)
- Modifying the target site so that it is not recognised by the antibiotic
- Metabolic bypass (multiple pathways for a particular reaction)
What misuse of antibiotics can lead to antibiotic resistance?
- Prophylactic use
- Incorrect prescribing
- Not finishing a course
What enzyme can break down penicillin?
What does it break penicillin down into?
Beta-lactamase
Penicilloic acid
What are the two mechanisms of genetic change?
Vertical gene transfer
• Mutation and evolution
Horizontal gene transfer
• Same generation transfer of genes
What are the three mechanisms of horizontal gene transfer?
- Transformation
- Transduction
- Conjugation
Describe transformation with regard to horizontal gene transfer
Uptake of naked NDA from the environment and incorporation into recipient in a heritable form
- Free DNA binds to DNA binding proteins in the cell membranes of the bacterium
- This protein breaks this down into a single-strand, which is fed inside of the cell
- Competence specific proteins binds to this single-stranded DNA and guides the DNA
- The DNA is fed into the chromosome of the cell
- If a gene is present, it is expressed, if this gene increases virulence, the cell will now have a survival advantage
Describe transduction with regard to horizontal gene transfer
Transfer of bacterial DNA via a bacteriophage - can be GENERALISED or SPECIALISED
• The bacteriophage picks up some host DNA during its assembly
• This is delivered to a new cell when the bacteriophage is released
Describe conjugation with regard to horizontal gene transfer
A donor cell makes contact with a recipient cell and DNA is transferred
• The ‘male donor’ status is determined by the presence of an extrachromosomal length of double stranded DNA called a ‘transmissible plasmid’
• Direct contact occurs, instigated by ‘conjugation apparatus’
• Sex pili of donor cell binds to recipient receptor
• A pore forms between the two cells cytoplasms
• The plasmid is cleaved into two single stranded lengths of DNA
• One enters the female cell, the other remains in the male cell
• The single strand is replicated into a double strand in both cells
• The cells detach, the recipient becomes a donor and becomes male due to plasmid presence
IMG 114
What type of bacteria is most likely to undergo conjugation?
Gram-negative
although plasmids can transfer between different species
What are the three types of plasmid?
1) R-plasmids 0 genes for antibiotic resistance
2) Virulence plasmid - genes which effect virulence
3) Metabolic plasmids - genes that affect metabolism