البكتيريا المراوغة Flashcards
Bacteria are capable of becoming resistant through several mechanisms
- Decreased Permeability
- Efflux Pump
- Degrading enzyme
- Alteration in target molecule
Increase efflux
Pumping out the antibiotic faster than it gets in
Give me example about antibiotic that resistance by Increase efflux
tetracyclines
Give me example about antibiotic that resistance by Reduce cellular uptake / Decreased the penetration
imipenem
Reduce cellular uptake
membrane becomes impermeable for antibiotic
Inactivation of the drug (Degrading enzyme)
some bacteria have enzymes that cleave or modify antibiotics
Give me example about antibiotic that resistance by Inactivation of the drug / Degrading enzyme
b lactamase inactivates penicillin and cephalosporin
Alteration of the target site
antibiotic cannot bind to its intended target because the target itself has been modified
Resistance has two types mey be :
- Inherent, intrinsic or innate resistance :
The properties of the bacterium are responsible for preventing the antibiotic action. - Acquired or extrinsic resistance :
It occurs when bacteria which were previously susceptible become resistant after exposure to certain antibiotic
Example about Intrinsic resistance
Ex. Intrinsic resistance to Gram-negative bacteria is thought to be
associated with the outer cell membrane, preventing certain antibiotics
from reaching their intracellular targets
Differences between Intrinsic and Extrinsic?
Intrinsic resistance is always chromosomally mediated
Acquired resistance may occur by mutations in the chromosome or by the acquisition of genes coding for resistance from an external source normally via a Plasmid or Transposon
give me type of bacteria that have Natural (Inherent) Resistance
(non-genetic natural resistant to AMA )
- Mycoplasmas
- Sporulated bacteria
- Tuberculosis
- Spheroplasts and protoplasts
Genetic basis of acquired resistance , there are three genetic elements are responsible for acquired resistance:
- Chromosomal mutations
- Plasmids
- Transposons
Chromosomal mutations could result in development of antibiotic resistance in genes due to changes
in the DNA sequence (point or frame shift)
M. tuberculosis where a minority population of organisms are resistant to which antibiotic ?
isoniazid
and eventually result in overgrowth by this subpopulation of resistant organisms.
Plasmid
Extrachromosomal piece of DNA codes for a number of properties including antibiotic resistance
Transposons
They are jumping genetic elements capable of transferring or transposing independently from one DNA molecule (chromosomes or plasmids) to another
True or False
The central region of the transposon often codes for antibiotic resistance genes.
ترو طبعاً
Mechanisms of Acquired Resistance
1- Reduction in cellular permeability to the antibiotic
2- Production of drug-inactivating enzymes.
3. Efflux Pump
4- Change in the antibiotic target site
5- Switch to alternative metabolic pathways unaffected by the drug.
6-Increased production of essential metabolite: that out compete antibiotic (e.g. increased production of PABA confers
resistance to sulfonamides).
Note: PABA is para-aminobenzoic acid that is used in DHF synthesis
Types of Cells Reduction of cellular permeability
1.Alteration of porins
affect antibiotics uptake e.g. chloramphenicol and cephaloridine
2.Antagonist of Ab-transport process
e.g. tetracyclines and erythromycin (decreasing influx or increasing efflux)
3.Loss of transport process
alanine transport system in case of cycloserine
4.Absence of transport system
aminoglycosides Abs and anaerobes (O2 transport system).
Types of Production of Drug-inactivating Enzymes
- b-lactamases: convert penicillins and cephalpsporins into toxic penicilloic and cephalosporic acids.
- Cross-resistance often occur
معلومة .
b-lactamases are inducible (G +ve) and constitutive (G –ve) enzymes
.
Cross-resistance often occur via (chromosome, plasmid , Transposons)
plasmid (R factor) or chromosome
Cross-resistance :
a single resistance mechanism confers resistance to an entire class of antibiotics. An example is the aminoglycoside modifying enzymes which may confer resistance to several members of the aminoglycoside family.
Bacterial efflux pumps
Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds of cells
They are active transporters
Yes or No
Bacterial efflux pumps require a source of chemical energy to perform their function
Yes
Resistance to ß-Lactam antibiotics caused by
A. ß-Lactamases (most common)
B. Mutation in penicillin- binding proteins (reduce affinity) (most common)
C. Reduce uptake (less significant)
D. Efflux (less significant)
ß-Lactamases may be (Chromosomal, Plasmid, Transposons)
chromosomal or plasmid-borne
ß-Lactamases have four classes :
A, B, C and D based on peptide base
Class A highly active against benzyl penicillin (Penicillin G)
Class B (ß-Lactamase) are effective against penicillin’s and cephalosporins
Resistant organisms:
- Enterobacter cloacae (chromosomal)
- P. aeruginosa (chromosomal)
- Klebsiella pneumoniae (plasmid)
- E. coli (plasmid)
True or False
Altered PBPs are responsible for reduce sensitivity to ß-Lactam antibiotics
True
Alter the penicillin binding proteins (PBPs) This mainly occur in:
- Streptococcus pneumoniae
- Haemophilus influenza
- MRSA (the most clinically significant)
Resistance to Glycopeptides Antibiotics
like Vancomycin, teicoplanin
The greatest resistant strain in Resistance to Glycopeptides Antibiotics is
enterococcal
Five types of Resistance to Glycopeptides Antibiotics, the most important is
Van A gene
Resistance to Glycopeptides Antibiotics mediated by
gene clustering
True or false
Van A resistance could transfer to MRSA
True
The most common mechanism for aminoglycosides resistance is
Their structural modification by enzymes expressed in resistant organisms
Three classes of enzymes that Resistance to Aminoglycoside
- Aminoglycoside phosphatase
- Aminoglycoside nucleotidyltransferase
- Aminoglycoside acetyltransferase
Resistance to Tetracycline
Resistant microorganisms:
- Shigella flexneri
- Salmonella enterica
- MRSA
- Streptococcus pneumoniae
Mechanism of resistance to Tetracycline
- Efflux (G –ve)
2. Ribosomal protection (G +ve), which mediated by cytoplasmic proteins that inhibit tetracycline
Fluoroquinolone bind and inhibit two enzymes :
- DNA gyrase
- topoisomerase IV which required for strand separation during cell division
In G-ve bacteria Fluoroquinolone inhibit DNA gyrase
In G+ve bacteria Fluoroquinolone inhibit both enzymes
Mechanisms of resistance to Fluoroquinolone
In G-ve bacteria changes in outer-membrane permeability associated with their resistance and efflux (E.coli)
In G+ve bacteria, efflux is the mechanism of resistance (S. aureus)
تذكير
Chloramphenicol inhibit protein synthesis (50S ribosome)
.
Mechanisms of resistance to Chloramphenicol
- In G-ve bacteria changes in outer-membrane permeability associated with their resistance and efflux
- The major resistant mechanism is drug inactivation by Chloramphenicol acetyltransferase this occur in both G-ve and G+ve bacteria
تذكير
macrolide, streptogramin inhibit protein synthesis by binding to target site on the ribosome
.
Mechanisms of resistance to macrolide, streptogramin
- In G-ve bacteria changes in outer-membrane permeability associated with their resistance
- In G+ve bacteria three mechanisms.
A- target site modification (methylation to the ribosomal target) (Strep. pneumoniae)
B- efflux (S.aureus)
C- Drug modification (Esterases, nucleotidyltransferases and phosphotransferases)
Mechanisms of resistance to Trimethoprim
- Overproduction of host DHFR
2. Mutation in the structural gene for DHFR
Mechanism of Resistance to peptide (polymyxin)
Polymyxin has self promoted uptake across the cell membrane and perturb the cytoplasmic membrane barrier
Resistance in G-ve bacteria due to change in lipopolysaccharide component
Multiple drug resistance develops among certain pathogens include
- S. aureus (MRSA)
- Enterococci
- Mycobacterium tuberculosis
What are the resistance mechanisms M. tuberculosis / multi drugs resistance has?
These are resistant to many antibiotics
1. Acquisition of conjugative plasmid (R-factor)
2. Multidrug efflux pumps, which can excrete a wide range of compounds where there is no or little chemical similarity
The common characteristic the agents with hydrophobic domain.
Mutants resistant to low levels of chloramphenicol, tetracyclines, rifampicin, penicillins and quinolones, due to impaired uptake of the antibiotics have been identified and are widespread
Multidrug efflux proteins: plasmid or chromosomal mediated, specific export proteins.
Antibiotic resistance to M.tuberculosis
Tetracyclines, Quinolones, chloramphenicol, erythromycin, β-lactams , rifampicin and others
Prevention of Antibiotic Resistance
- Only use an antibiotic when they are likely to be beneficial
- Do not take an antibiotic for a viral infection like a cold, most sore throats or flu
- Do not save any of your antibiotic prescription
- Take an antibiotic exactly as the doctor tells you
- Do not take an antibiotic that is prescribed for someone else
Overcoming Antibiotic Resistance
- Altering the use of existing antibiotics
A. Decrease the duration of the antibiotic so the organism does not create
resistance
B. Increase the dosage of the antibiotic for a higher concentration of drug
C. Discontinue use of an antibiotic - Rotation (cycling) of antibiotics used in treatment
Especially useful when used with last resort treatments - Combination (mixing) of antibiotics in a treatment
Minimizes possibility of resistance since the organism needs two ways to get rid of antibiotics
Drug resistance problem
- Resistance will NOT occur once enough antibiotic and time are given to cause a clinical problem
Penicillin-resistant Streptococcus pneumoniae took 25 years to become a clinical problem - Organisms that are resistant to one antibiotic will probably become resistant to others
Neisseria gonorrhoeae was first resistant to penicillin before tetracycline
3.Drug resistance will not disappear, although it may decline slowly – the decrease is associated with poorly reversible genetic and environmental factors
Neisseria gonorrhoeae was first resistant to penicillin before tetracycline
TRUE
