MDR Multi Drug Resistance Bacteria AntiMicrobial & Chemotherapeutics.pptx
1. Resistant Organisms can be:
■ Drug Tolerant:
Loss of affinity of the target biomolecule of the organism for a particular AMA,
E.g. resistant Staphylococcus Aureus & E-Coli develop a RNA polymerase that
does not bind to Rifampicin.
■ Drug Destroying:
The resistant microbe elaborates an enzyme which inactivates the drug
E.g. B- lactamases are produced by staphylococcus Hymophylus which inactivates
Penicillin G.
2. ■ Drug Impermeable:
Many hydrophobic antibiotics gain access in to the bacterial cell through specific
channels formed by proteins called porins or need specific transport mechanism.
Active efflux based resistant has been detected by the bacteria may also acquire
plasmid directed inducible energy dependent efflux protein in their cell membrane
which pump out tetracycline.
■ Cross Resistance:
Acquisition of resistance to AMA confirming resistant to another AMA, to which the
organism is not to been exposed is called cross resistant. Sometimes unrelated
drugs show partial cross-resistant
E.g. Between tetracycline & chloramphenicol.
3. Multi-Drug Resistance
■ Multiple drug resistance or Multidrug resistance is a condition
enabling a disease-causing organism to resist distinct drugs or
chemicals of a wide variety of structure and function targeted at
eradicating the organism.
■ Organisms that display multidrug resistance can be pathologic
cells, including bacterial and neoplastic cells.
■ Multidrug-Resistant Organisms (MDROs) are defined as
microorganisms that are resistant to one or more classes of
antimicrobial agents.
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9. Bacterial Resistance to Antibiotics:
■ Various microorganisms have survived for thousands of years by
their being able to adapt to antimicrobial agents. They do so via
spontaneous mutation or by DNA transfer.
■ It is this very process that enables some bacteria to oppose the
assault of certain antibiotics, rendering the antibiotics ineffective.1
10. Mechanisms in Attaining Multidrug
Resistance
■ No longer relying on a glycoprotein cell wall
■ Enzymatic deactivation of antibiotics
■ Decreased cell wall permeability to antibiotics
■ Altered target sites of antibiotic
■ Efflux mechanisms to remove antibiotics
■ Increased mutation rate as a stress response
11. Resistance can be;
Active :
(i.e., the result of a specific evolutionary
pressure to adapt a counterattack mechanism against an
antibiotic or class of antibiotics).
Passive :
(where resistance is a consequence of general
adaptive processes that are not necessarily linked to a
given class of antibiotic; e.g., the non-specific barrier
afforded by the outer membrane of Gram-negative
bacteria).
12. Bacteria achieve active drug resistance through three major
mechanisms:
(1) Efflux of the antibiotic from the cell via a collection of
membrane-associated pumping proteins
(2) Modification of the antibiotic target (e.g., through mutation of
key binding elements such as ribosomal RNA or even by
reprogramming of biosynthetic pathways such as in resistance to
the glycopeptide antibiotics)
(3) Via the synthesis of modifying enzymes that selectively target
and destroy the activity of antibiotics.
13. All of these mechanisms require new genetic programming by the cell
in response to the presence of antibiotics. In fact, in several cases,
the antibiotics or their action actually genetically regulate the
expression of resistance genes. Therefore, bacterial cells expend a
considerable amount of energy and genetic space to actively resist
antibiotics. This review is focused on enzymes that confer resistance
to antibiotics. These are a remarkable set of adaptive proteins that
utilize a broad cadre of strategies to confer drug resistance. The
review will make an inventory of these mechanisms and discuss their
origins and evolution, focusing primarily (but not exclusively) on
clinical resistance mechanisms for the sake of coherence and brevity.
14. Evolution of Enzymatic Resistance
Antibiotic inactivation mechanisms share many similarities with well-
characterized enzymatic reactions. Hydrolysis, group transfer, and
redox enzymes are all involved in primary and intermediary microbial
metabolism and, thus, likely serve as the origins of resistance. As
noted several times above, primary sequence analysis of resistance
proteins, and in particular determination of their molecular
mechanisms and three-dimensional structures.
15. To Limit the Development of Antibiotic
Resistance, One Should:
■ Use antibiotics only for bacterial infections.
■ Identify the causative organism if possible.
■ Use the right antibiotic; do not rely on broad-range antibiotics.
■ Not stop antibiotics as soon as symptoms improve; finish the full
course.
■ Not use antibiotics for most colds, coughs, bronchitis, sinus
infections, and eye infections, which are caused by viruses.
16. Neoplastic Resistance:
■ Cancer cells also have the ability to become resistant to multiple
different drugs, and share many of the same mechanisms:
■ Increased efflux of drug (as by P-glycoprotein, multidrug
resistance-associated protein, lung resistance-related protein, and
breast cancer resistance protein)
■ Enzymatic deactivation (i.e., glutathione conjugation)
■ Decreased permeability (drugs cannot enter the cell)
■ Altered binding-sites
■ Alternate metabolic pathways (the cancer compensates for the
effect of the drug).
■ Of these mechanisms common one is efflux of drugs mediated by
one of energy dependent transporters, known as ATP binding
cassette transporter.
