Bacteriology - General structure & AMR Flashcards
What are the main methods of antibiotic actions?
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
- Anti-metabolites
How many AMR be mediated?
- chromosome-mediated
- plasmid-mediated
- transposon-mediated
Describe chromosome-mediated resistance
- due to mutation in gene that codes for the target of the drug, or the transport system in the membrane that controls uptake
Why is plasmid-mediated resistance clinically important?
- occurs in many different species
- plasmids frequently mediate resistance to multiple drugs
plasmids have a high rate of transfer
What are transposons?
Genes that are transferred either within or between larger pieces of DNA, such as the bacterial chromosome, and plasmids
What is a typical drug-resistance transposon composed of?
3 genes, flanked by shorter pieces of DNA - the genes code for…
- transposase (enzyme that catalyses the excision and reintegration of the transposon)
- a repressor that regulates synthesis of the transposase
- the drug resistance gene
What is vertical gene transfer?
Occurs through replication
What are the three methods of HGT?
- Conjugation
- Transduction
- Transformation
What is conjugation?
between two bacterial cells in direct contact
What is transduction?
Injection of foreign DA into the host bacterium by a bacteriophage virus
What is transformation?
Uptake of naked genetic material fragments through cell membranes, recombined with bacterial chromosome of the recipient
The transfer of antibiotic resistance genes from one strain of bacterium to another via a virus is called
transduction
The transfer of antibiotic resistance genes from one strain of bacterium to another via uptake of nakedDNA is called
transformation
What are the five main mechanisms that mediate bacterial resistance to drugs?
1 - production of enzymes that inactivate the drug
2 - synthesis of modified targets against which the drug has reduced effect
3- reducing permeability to the drug such that an effective intracellular concentration of the drug is not achieved
4 - actively export drugs using a ‘multidrug resistance’ pump which imports proteins in exchange for a variety of foreign molecules, including antibiotics
5 - target amplification
What are the major categories of antibiotics?
- cell wall inhibitors
- protein synthesis inhibitors
- nucleic acid synthesis inhibitors
What are the main types of cell wall inhibitors
- beta lactams
- vancomycin
- isoniazid
Give examples of beta lactams
- penicillin
- amoxicillin
- benzylpenicillin
- flucloxacillin
- cephalosporins
How do beta lactams work?
They irreversibly inhibit transpeptidase, causing osmotic rupture of the bacteria
How does vancomycin work?
Prevents transpeptidase from binding and catalysing cross-link formation
How does isoniazid work?
Inhibits synthesis of long chain mycolic acids required for bacterial wall and capsule
The most common mechanism of resistance to penicillin and cephalosporin antibiotics found inantibiotic resistant strains of bacteria is
beta-lactamases (but also altered penicillin-binding proteins and decreased permeability via GNB efflux)
What two classes of antibiotic affect the 30S subunit?
Aminoglycosides
Tetracyclines
What do aminoglycosides do?
Bind to 30S so it cannot bind with 50S and an mRNA for form the initiation complex
What do tetracyclines do?
Bind to 30S, preventing aminoacyl-tRNAs from entering the donor site in the ribosome
Example of aminoglycosides
streptomycin
gentamycin
tetracycline
Example of tetracycline antibiotic
Doxycycline
What two classed of antibiotic act in the 50S subunit?
Chloramphenicol
Macrolides
What does chloramphenicol do?
Binds to 50S and prevents peptidyltransferase
What do macrolides do?
Bind to 50S and prevent release of uncharged tRNA so donor site remains occupied
Example of macrolide
Erythromycin
Whichantibiotic is limited in use by resistance caused by increased drug efflux and changes to thehigh affinity binding site on the 70S ribosomal subunit?
Erythromycin
What does MRSA stand for?
Methicillin-resistant Staphylococcus aureus
What are the different classes of nucleic acid synthesis inhibitors?
Folic acid synthesis inhibitors
Gyrase inhibitors
transcription inhibitors
Examples of folic acid synthesis inhibitors
Sulfonamides and trimethoprim (which is a 2,4-diaminopyridine)
Examples of gyrase inhibitors
Quinolones → ciproflaxacin
Example of transcription inhibition
Rifamycin → RNA pol inhibitor
Which antibiotic is unique to mycobacteria?
Isoniazid
Are sulphonamides (antifolates) commonly used?
No, because of resistence
What are colonies usually measured in?
mm
Typical size of a bacterium
1 micrometer
What is a nucleoid?
Found in bacteria
Nucleus that lacks a nuclear membrane
What is peptidoglycan composed of?
N-acetylglucosamine
N-acetylmuramic acid
Describe Gram positive bacteria
Thick cell wall containing lipoteichoic acid and an inner cell membrane
Describe Gram negative bacteria
Have a phospholipid outer cell envelope containing a high concentration of polysaccharide and protein, thin cell wall and inner cell membrane
What do flagella aid?
Motility
What do fimbriae aid?
Adherence
How many base pairs in bacterial genome?
1-6million
How many base pairs are plasmids?
0.1Mbps
What are the physical methods of treating bacterial infection?
- Surgical draining e.g. of abscesses
- Debridement (removal of damaged tissue or foreign objects from a wound) e.g. in necrotising fasciitis
Example of mechanism of aminoglycoside resistance
Phosphotransferases
Example of cell wall impermeability leading to AMR
mutant porins in Gm-neg bacteria
What does gyrase do?
Required for negative supercoiling of bacterial DNA
How many secretion systems have been identified?
7
What body compartments are normally sterile?
Blood, lymph and CSF
What is pasteurisation?
Process in which packaged and non-packaged foods are treated with mild heat to eliminate pathogens and extend shelf life
What is autoclaving?
Method of sterilisation that uses high-pressure steam
What can be used for sterilisation and disinfection?
Pasteurization Autoclaving Hypochlorite Halogenated phenols Gamma-irradiation
What is peptidoglycan made up of?
Polymer of NAG (N-acetylglucosamine) and NAM (N-acetylmuramic acid)
What do lipoteichoic acids do?
Serve a chelating agents, and also types of adherance
What sort of environments are G+ bacteria more likely to survive? Why?
Dry environments, e.g. the skin, due to thick peptidoglycan layer
What sort of environments are G- bacteria more likely to survive in?
Places such as the gut
Surface is hydrophilic but lipid components give hydrophobic character as well
Does the cell surface of G- or G+ permit spore formation? Give two examples of genuses this occurs in?
Positive
Bacillus and Clostridium
How may antibiotic resistance occur in G- bacteria?
They have outer memvranes with hydrophobic lipid bilayers and porins with size exclusion properties
Only small hydrophilic antibiotics can pass
Resistance can be caused by loss of function change of porins
Which antibiotics are hydrophobic and can diffuse across the bilayer?
Aminoglycosides
Macrolides
Rifamycins
Which type of bacteria utilise secretion systems? Why can only this type use secretion systems?
Gram -
Because of their outer membrane
Which type of bacteria produces OMVs? What do OMVs do?
Gram negative
Allow communication of bacteria with each other, other microorganisms and the host
