PMB: AB resistance 7 Flashcards
What effect do AB have on bacteria?
- Many bacteria are sensitive to AB
- They either kill them or have their growth slowed (can be outcompeted)
- Some are not effected and can avoid this problem
What does it mean when a bacteria is antibiotic resistant?
What happens when the concentration of AB is increased
AB Resistance decribes a situation where a type of bacteria (species or stranin) is not susceptible to the active concentration of the antimictobial
At higher concentrations the AB may still have an effect on the bacteria
What can bacterial resistance to AB be from?
- Intrinsic properties
- Accquired characterisitis
What happens in instrinsic resistance
- the bacteria is able to continue normal function in the presence of ABs.
- This is due to expressions of genes which synthesise constituents which protect the cells. These mean the AB is not able to exert its full effect e.g. capsule formation
What types of bacteria is intrinsic resistnace tend to be seen in and why?
- Normally seen in gram negatvie bacteria due to their more complex cell wall - mainly LPS layer
How does the LPS in Gram negative bacteria prevent AB effect?
The LPS layer is hydrophobic, whereas a lot of anitmicorbial compounds are hydrophillic. This hydrophobicity limits entery of these hydrophillic compounds and prevents them froma ccessing the part of the cell they are likely to be effective.
The outer membrane is spanned with porins (barrel shaped hydrophillic proteins), which act as channelsn (pores), allowing movement of molecules from outside of the cell to the timside.
Only small molecules of below <600 Daltons can pass through into the periplasm so larger molecules have a porblem.
Discuss AB resistance and Gram positive species
Gram positive bacteria lack the LPS layer therefore do not have the same level of blockage to molecules. This allows passage of considerably larger molecules (<- 30kDa) to pass through the peptifoglycan
What other methods are classed as intrisinic resistace?
- Secretion of exopolysacchardie helps to produce a biofilm which helps protect both gram positive and gram negatvie bacteria by giving them instrinci resitance. Antimicrobials are generally unable to penetrate this biofilm matrix therefore do not manage to reacvhj the bacteria
- Some bacteria produce enzymes which are able to degrade antimicrobials e.g. pseudomonas aeruginosa can degrade benzoic acid or quaternsary ammonium compounds
Describe the basic process of Acquired resistacne
- In order for bacteria to accquire AB or AMC resistance they are required to alter their genetic mateiral/ genotype
- This can be done in 2 ways:
- Accquisition of new genes (HGT/LGT)
- Mutation following exposure to antimicrobial
Horizontal/ lateral genes transfer
What is chromaosme mutations, examples and how do they impact on accquiring resistance?
- A mutation is an alteration in the base sequence of DNA
- Mutaions involve changing the genetic material of the cell
- Examples: Deletion, insertion, inversion, point substitutions
- Mutations lead to AB resistnace by either of 2 ways:
- Lead to increased synthesis of cell materia that leads to Resistance Or
- Decrease production of antimicrobial target
Give details about Serratia marcescens
Serratia marcescens
- Gram negative rod
- Member of family Enterobacteriaceae
- Human pathogen
- Involved in hospital-acquired infections
- Particularly
- urinary tract infections
- catheter-associated bacteremia
- wound infections
Give an example of an AB that can be used against S.Marcescens.
Discuss this example in realtion to tolerance
QACs can be used against S.Marcenscens (AB)
However, it was found that at sublethal levels the bacteria developed resistance to normally lethal levels
This was due to the mutation stimulating increased LPS lipid production, leading to the cells becoming impermbeable to QACs
Describe how bacteria with accquired characteristics gained AB resistance by the process of acquistion of new genes.
Give an example of bacteria which are resistant
- Bacteria can acquire new genes by the transfer of DNA between organisms
- Normally these genes are carried and transfered via plasmids termed resistance (R) factor
- There are a large number of R factors with different modesof actions and have been found in different species of bacteria.
- Examples include bactera expressing reistance to the AB b-lactam e.g. New Dehli metallo-b-lactamase 1
- How are R factors typicall transferred?
- What other mechanisms exist?
- What is it termed when transfer occurs between a) the SAME species b) DIFFERENT species
- Transfer of R factor tends to occur via plasmid conjugation
- Can also occur via transduction and transformation
- a) intraspecific b) interspecific
What happens during the conjugation process?
- The donor strain retains a copy of the plasmid. The recipent can then become a future donar. The process occurs via a logarithmic scale therofre allowing a rapid spread