iii. Microbial antibiotic action and mechanisms of bacterial resistance Flashcards
Mechanism of action of antibiotic agents: (8)
Inhibit cell wall synthesis:
- Β-lactams: (2)
o Β-lactam antibiotics contain a β lactam ring in their molecular structures
o Work by inhibiting peptidoglycan cross-linkage
Peptidoglycan is an important component of the cell wall of GP and GN organisms. When this cross-linkage does not occur, there is disruption of the cell wall.
- Β-lactams include: (5)
▪ Penicillins
▪ Β-lactam inhibitor combinations (amoxicillin, clavulanate)
▪ Cephalosporins (1-5)
▪ Monobactams
▪ Carbapenems
Inhibit cell wall synthesis:
- Glycopeptides: (2)
o Inhibit peptidoglycan cross-linking in gram positive organisms
o Example: Vancomycin, teicoplanin
Inhibit cell wall synthesis:
- Fosfomycin:
o Inhibits the enzyme pyruvyl transferase during the first step of peptidoglycan synthesis.
Disrupt cell membrane:
- Lipopeptides: (3)
o Binds irreversibly to the cytoplasm membrane of bacteria resulting in disruption of cellular ion concentration gradients. This causes cell death.
o Activity against Gram-positive bacteria.
o Example: Daptomycin
Disrupt cell membrane:
- Polypeptides: (2)
o Detergent-cationic property: Disrupts the lipid component of the cytoplasmic membrane of gram-negative bacteria leading to cell death.
o Example: Polymixin B, Polymixin E (Colistin: Antibiotic used for salvage therapy in extensively drug-resistant gram-negative infections)
Inhibit DNA:
- Inhibit DNA replication:
How does this occur? (2)
o Quinolones
o Inhibit bacterial DNA gyrase and topoisemerase required for DNA uncoiling leading to inhibition of DNA replication and eventually cell death.
- Inhibit DNA replication:
o Different classes of quinolones: (4)
How is DNA inhibited? (4)
- Inhibit DNA replication
- Inhibit DNA transcription
- Inhibit DNA function
- Inhibit DNA synthesis
- Inhibit DNA transcription:
o Rifamycins:
Acts by binding to bacterial DNA dependant RNA polymerase, resulting in inhibition of RNA synthesis.
Example: Rifampicin
- Inhibit DNA function:
o Metronidazole:
Receives electrons under anaerobic conditions and forms toxic metabolites that damage bacterial DNA.
- Inhibit DNA synthesis:
o Sulphonamides and trimethoprim/bactrim:
Act by inhibiting the synthesis of tetrahydrofolate which is necessary for bacterial DNA synthesis.
What are the types of
Antibiotic Resistance? (2)
- Intrinsic resistance
- Acquired resistance
What is - Intrinsic resistance? (3)
What is acquired resistance? (2)
o Changes in usual genetic makeup of a microorganism. Bacteria acquires this resistance with repeated exposure to antibiotics – Often seen
in the hospital setting.
o The resistance is unpredictable
Mechanisms of acquiring resistance genes in bacteria: (3)
- Transformation
- Conjugation
- Transduction
Mechanisms of acquiring resistance genes in bacteria:
- Transformation: (3)
o Bacteria acquire new genetic material from the environment
o Resulting in an altered gene with altered affinity for antibiotic
o Example: Streptococcus pneumoniae can acquire short fragments of penicillin binding protein (PBP) genes from closely related species to form a new PBP that has less affinity for penicillin and therefore resistance develops.
Mechanisms of acquiring resistance genes in bacteria:
- Conjugation: (6)
Mechanisms of acquiring resistance genes in bacteria:
- Transduction: (4)
o Transfer of DNA from one bacterium into another via bacteriophages (A virus that infects bacteria). Virus carries mechanism of resistance and takes it into a bacterial cell, thereby bacteria can also develop the mechanism of resistance.
o When a bacteriophage infects a bacterium, it takes over the bacteria’s genetic processes to produce more phage.
o Bacterial DNA may be incorporated into the new phage DNA during this process.
o Once the bacteria die these new phage go on to infect other bacteria with genes from the previously infected bacterium. When virus moves from one bacterial organism to another, it can acquire additional genes (some which may have mechanisms of resistance) – Mode of transmission of resistance from one bacterial organism to another.
Mechanisms of acquired resistance:
- Genetic material can also be transferred by _______ & ________ (jumping genes) Both are mobile genetic material
INTEGRONS & TRANSPOSONS
Mechanisms of acquired resistance:
- INTEGRON:
- INTEGRON: “Gene cassette”. Mobile egentic material that can enter into bacterial organisms but need to attach to specific sites on the DNA of the bacterial organism. Advantage of an integron – Also has its own mechanisms to express that particular gene (positive regular, negative regulator for gene). Therefore, it can express the gene without additional genetic support from the host bacterial DNA.
Mechanisms of acquired resistance:
- TRANSPOSONS:
- TRANSPOSONS: Mobile genetic material. Can move from one bacterial organism to another. They do not have any specific site of integration into the host’s DNA (can combine at any point). Cause modification to the host-bacterial DNA.
Mechanisms of acquired resistance:
- Resistance can also occur with time – A normal mutation could occur based on the exposure of the organism to various ______ (Naturally occurring chromosomal mutation that would occur over time following exposure to antibiotics).
antibiotics
