ANTIBIOTICS RESISTANCE (.pptx_20251007_121508_0000.pdf

Antibioti and the resistance of microorganisms towards antibiotics

1. ANTIBIOTICS RESISTANCE!
THE SILENT TSUNAMI!!
JASNA
II MSc.MICROBIOLOGY

2. Objectives Background
Why antibacterial resistance is a concern?
How antibacterials works?
Mechanisms of resistance to antibacterials
Generation of antibiotics
Conclusion
References

3. antibiotic resistance!
The ability of bacteria and other micro-organisms to with stand to an antibiotics and inhibit
the antibiotics at the site of infection called antibiotics resistance.
In 1945 Fleming himself warned of the danger of resistance – According to him
““It is not difficult to make microbes resistant to penicillin in the laboratory by exposing
them to concentrations not sufficient to kill them, and the same thing has occasionally
happened in the body.
OR
by exposing his microbes to non-lethal quantities of the drug make them resistant.”

4. History of resistance
Throughout history there has been a continual battle between
human beings and multitude of micro-organisms that cause
infection and disease.
Penicillin was successful in controlling bacterial infections
among World War II soldiers.
However, shortly thereafter, penicillin resistance became a
substantial clinical problem.
In response, new beta-lactam antibiotics were discovered,
developed, and deployed, restoring confidence.
Figure in next slide show the variation and increase in the
antibiotic resistance

5. ANTIBIOTIC RESISTANCE CAUSES

6. Why resistance is a concern! threat
Resistant organisms lead to treatment failure
Increased mortality
Resistant bacteria may spread in Community
Low level resistance can go undetected
Added burden on healthcare costs
Threatens to return to pre-antibiotic era
Selection pressure

7. How Antibiotics work?
4 Ways Antibiotics Affect Bacterial Cells:
Disrupt cell wall synthesis
Inhibit metabolic pathway
Inhibit protein synthesis
Inhibit DNA replication

8. How the antibiotics degrade the bacterial
cell wall:
Most bacteria produce a cell wall that
is composed partly of a macromolecule
called peptidoglycan, itself made up of
amino sugars and short peptides. 
Human cells do not make or need
peptidoglycan.
Penicillin, one of the first antibiotics to
be used widely, prevents the final cross-
linking step, or transpeptidation, in
assembly of this macromolecule. 
The result is a very fragile cell wall that
bursts, killing the bacterium.
No harm comes to the human host
because penicillin does not inhibit any
biochemical process that goes on
within us.

9. Inhibit metabolic pathwayBacteria can also be selectively eradicated
by targeting their metabolic pathways.
Sulfonamides, such as sulfamethoxazole,
are similar in structure to para-
aminobenzoic acid, a compound critical
for synthesis of folic acid. 
All cells require folic acid and it can
diffuse easily into human cells.
But the vitamin cannot enter bacterial
cells and thus bacteria must make their
own. 
The sulfa drugs such as sulfonamides
inhibit a critical enzyme--dihydropteroate
synthase--in this process.
Once the process is stopped, the bacteria
can no longer grow.

10. Inhibit protein synthesis Another kind of antibiotic—tetracycline, also inhibits bacterial growth by stopping
protein synthesis.
Both bacteria and humans carry out protein synthesis on structures called
ribosomes.
Tetracycline can cross the membranes of bacteria and accumulate in high
concentrations in the cytoplasm. 
Tetracycline then binds to a single site on the ribosome--the 30S (smaller)
ribosomal subunit--and blocks a key RNA interaction, which shuts off the
lengthening protein chain.
however, in human cells tetracycline does not accumulate in sufficient
concentrations to stop protein synthesis.

11. Inhibit DNA replication
DNA replication must occur in both bacteria and human cells.
The process is sufficiently different in each that antibiotics such as
ciprofloxacin--a fluoroquinolone notable for its activity against the
anthrax bacillus--can specifically target an enzyme called DNA gyrase in
bacteria.
This enzyme relaxes tightly wound chromosomal DNA, there by allowing
DNA replication to proceed.
But this antibiotic does not affect the DNA gyrases of humans and thus,
again, bacteria die while the host remains unharmed.

12. Mechanisms of Resistance
The abilities of bacterial organisms to utilize the various strategies to resist
antimicrobial compounds are all genetically encoded.
Intrinsic resistance: is that type of resistance which is naturally coded and expressed
by all (or almost all) strains of that particular bacterial species.  An example of
instrinsic resistance is the natural resistance of anaerobes to aminoglycosides and
Gram-negative bacteria against vancomycin. 
Acquired resistance: Changes in bacterial genome through mutation or horizontal
gene acquisition,on the other hand, may consequently lead to a change in the
nature of proteins expressed by the organism. 
Such change may lead to an alteration in the structural and functional features of
the bacteria involved, which may result in changes leading to resistance against a
particular antibiotic.
 In fact, several different mechanisms may work together to confer resistance to a
single antimicrobial agent.

13. Strategy 1: Preventing access of antimicrobial moleculeAntimicrobial compounds almost always require access into the
bacterial cell to reach their target site where they can interfere with
the normal function of the bacterial organism.
Porin channels are the passageways by which these antibiotics
would normally cross the bacterial outer membrane.
Some bacteria protect themselves by prohibiting these antimicrobial
compounds from entering past their cell walls. For example, a
variety of Gram-negative bacteria reduce the uptake of certain
antibiotics, such as aminoglycosides and beta lactams, by modifying
the cell membrane porin channel frequency, size, and selectivity.
Prohibiting entry in this manner will prevent these antimicrobials
from reaching their intended targets that, for aminoglycosides and
beta lactams, are the ribosomes and the penicillin-binding proteins
(PBPs), respectively.
This strategy have been observed in: Pseudomonas
aeruginosa against imipenem (a beta-lactam antibiotic).
Many Gram-negative bacteria against aminoglycosides.
Many Gram-negative bacteria against quinolones.

14. Strategy 2: Modification of the antimicrobial target/ By Modification
or degradation
Some resistant bacteria evade antimicrobials by reprogramming or
camouflaging critical target sites to avoid recognition.
Therefore, in spite of the presence of an intact and active antimicrobial
compound, no subsequent binding or inhibition will take place.
Bacterial Resistance Due To Target Site Modification:
1.Alteration in penicillin-binding protein (PBPs) leading to reduced affinity of
beta-lactam antibiotics. i,e (Methicillin-Resistant Staphylococcus aureus, S.
pneumoniae, Neisseria gonorrheae, Group A streptococci, Listeria
monocytogenes).
2.A classic example is the hydrolytic deactivation of the beta-lactam ring in
penicillins and cephalosporins by the bacterial enzyme called beta
lactamase.  The inactivated penicilloic acid will then be ineffective in binding
to PBPs (penicllin binding proteins), thereby protecting the process of cell
wall synthesis. 
This strategy has also been observed in:
Enterobacteriaceae against chloramphenicol (acetylation).
Gram negative and Gram positive bacteria against aminoglycosides
(phosphorylation, adenylation, and acetylation).

15. 3. Eliminating antimicrobial agents from the cell with
expulsion via efflux pumps.To be effective, antimicrobial agents must also be present at a
sufficiently high concentration within the bacterial cell. 
Some bacteria possess membrane proteins that act as an export or
efflux pump for certain antimicrobials, extruding the antibiotic out of
the cell as fast as it can enter.
This results in low intracellular concentrations that are insufficient to
elicit an effect. 
Some efflux pumps selectively extrude specific antibiotics such as
macrolides, lincosamides, streptogramins and tetracyclines, whereas
others (referred to as multiple drug resistance pumps) expel a variety
of structurally diverse anti-infectives with different modes of action.
Staphylococcus aureus and Streptococcus pneumoniae against
fluoroquinolones.

16. Generation of Antibiotics
Generation term comes only in case of Penicillins and
Cephalosporins (Beta lactam antibiotics) and depending on their
action on the cell wall of gram positive and gram negative bacteria.
They are classified by using terms ‘ Broad spectrum’ and ‘Narrow
spectrum’ antibiotics.
1st Generation Antibiotics:
Have a narrow spectrum of clinical use (this means there are only a
few organisms that they are able to successfully treat with this class
of penicillin) .
Good for common gram-positive bacteria that cause ear and throat
infections, venereal diseases of gonorrhea and syphilis.
A very high number of the drugs in this group are resistant to
organisms that produce penicillinase.

17. 2ⁿᵈ and 3ʳᵈ Generation antibiotics 2ⁿᵈ generation antibiotics have an extended or Intermediate
spectrum of clinical use (Some gram +ve and gram-ve).
Not very effective against penicillinase producing organisms
3ʳᵈ generation antibiotics are broad spectrum and the effective
against both gram positive and gram negative bacteria.
However their optimum activity is against gram negative
bacteria. not resistant to penicillinase-producing organisms.
4th Generation Antibiotics are extended spectrum antibiotics.
They are not resistant to Beta lactamase producing
microorganisms.
5ᵗʰ Generation antibiotics are Extended spectrum Antibiotics.
Cephtaroline : Pneumonia, skin and soft tissue infection.
Cephtobiprole: Methicillin resistant Staphylococcus aureus.

18. Conclusion
The importance and value of antibiotics cannot be
overestimated; we are totally dependent on them for the
treatment of infectious diseases.
The best practice can be that doctors and health care centres
should provide their patients places that are resistance-free by
taking strict measures in infection control and antibiotic use.
There is no perfect antibiotic, and once the most appropriate
uses of any new compound are identified, it is essential that
prescription of the antibiotic be restricted to those uses.