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Infectious diseases remain one of the principal causes of morbidity and
mortality in the world .
Efflux pumps are elements that antibiotics are effective in resistance
and are involved in the pathogenesis of bacteria .
efflux pumps are important for processes of detoxification of
intracellular metabolites, bacterial virulence in both animal an Man
hosts, and etc .
So today we're in a selection pressure for antibiotic use and for
the treatment of bacterial infections are a new development .
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Efflux as a mechanism for antibiotic resistance was first
described in 1980
Multidrug efflux pumps cause serious problems in cancer chemotherapy
and the treatment of bacterial infections.
Antimicrobial resistance has been considered the new challenge of
the 21st century for example : Salmonella enterica , E coli
Different studies have demonstrated that MDR pumps are
capable of extruding not only antibiotics but also antiseptics.
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Efflux pumps involved in the excretion of drugs and chemicals.
Efflux pump protects microorganisms against antibiotics of chemicals and
toxins and stress.
Importance :
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The efflux pumps is responsible for the survival of microorganisms
in various environments
Efflux pumps involved in the synthesis of bacterial surface
structures
Efflux pumps involved in balance of solutions ,homeostasis , and
ionic balance
Importance :
7. The most important mechanisms of drug resistance:
• Inactivating
• Change the form of the drug
• The aim of antibiotic succession and delegation
• Increase the amount of target
• Reduced affinity:
Recombination
Modification enzymes
• Efflux pumps
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8. Efflux pumps which was first known : Efflux pumps was for a family of tetracycline
Bacterial efflux pumps are classified into five major superfamilies, based on the
amino acid sequence and the energy source
In the prokaryotic kingdom there are five major families of efflux transporters.
Classification :
13. Energy used in the efflux pump :
• The energy source:
• ABC transporters are dependent on ATP hydrolysis;
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• MFS, RND and SMR are proton-driven efflux pumps.
• MATE transporters consist of a Na/H drug antiporter system.
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)The primary active transport(
)Secondary active transport)
16. • Important note :
The resistance who efflux pump caused by antibiotic depends on the nature of microorganisms
and substrate
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17. Structure of drug efflux systems:
• In Gram-positive bacteria:
• A cytoplasmic membrane transport proteins that recognize specific substrate.
and led to resistance.
• In Gram-negative bacteria:
• 3 component in a system:
Two transport proteins within the membrane.
A periplasmic lipoprotein adapter
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19. ABC tranceporters :
• In contrast with Prokaryotes, the major mechanism of efflux in eukaryotes.
• energy source : hydrolysis of ATP.
• p-gp pump and MDR pumps. ( anticancer drug)
• ABC including : 200 amino acid
• LSGGQ sequence on all members of the family.
21. The SMR family :
• The unusual bacteria
• 100 amino acids that made the four-helix
• For example : EmrE is in E.coli
• QacH-2 in Staphylococcus aureus causes a resistance to number of disinfectants.
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22. The MFS family :
• In eukaryotes, bacteria and Archaea.
• MFS are made of 400 amino acids arranged in 12 Helix membrane and they heve cytoplasmic
loop between helices 6 and 7.
• Mfs transport of drugs have two classes:
1- Class B: Transport tetracycline in E Coli
2-class k: Transport tetracycline in Staphylococcus aureus
• MFS characterized is multi-drug pumps
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• transmission sugar and drugs.
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26. Structure :
• DNA structure is composed of 3 components:
1-AcrA: inner membrane.
2-AcrB: inner membrane.
3-TolC: in the outer membrane.
The third monomer forming the inner membrane creates an area that extends Periplasmic..
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27. TOLC PROTEIN
• a multifunctional protein.
• Moving in small drugs and toxins polypeptide.
• for example: hemolysin .
• TolC is divided into two domains:
1-domain beta : in the outer membrane.
2-domain alpha : in the periplasmic space.
TolC several actions have to cross the outer membrane periplasmic substrates.
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29. β-barrel :
• Opens into the outer membrane.
• Beta consists of 12 strings and are arranged in a right-handed barrel.
• Α-helical :
• 12 left-handed filament is composed of two types of grape :
Short
Tall
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35. MATE transporters :
• 450 amino acids
• arranged in 12 Helix .
• Na+ or protons.
• NorM in Vibrio parahaemolyticus resistance to color, aminoglycosides
and fluoroquinolones.
• YdhE in E.Coli resistance to antibiotics
• MepA in Staphylococcus aureus, tetracycline, detergents and colors .
• PepM in Pseudomonas aeruginosa substrate fluoroquinolones, is
ethidium bromide and disinfectants.
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