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CONCEPT NOTES ON :
“MICROORGANISMS ARE INCREASINGLY BECOMING
RESISTANT TO CONVENTIONAL ANTIBIOTICS:
DEVELOPMENT OF ANTIMICROBIAL AGENTS HAS
BECOME AN EMERGENCY NEED”
TEAM MEMBERS:
ARIJIT GOSWAMI (UG-IV)
PRITHA NAYAK (UG-IV)
ROHIT HALDER (UG-IV)
SOUVIK SIKDAR (UG-III)
MOLLA SALAUDDIN (UG-III)
WHAT IS ANTIBIOTICS &
ANTIMICROBIALS AGENTS ?
• Antimicrobial agent: A general term for drugs, chemicals, or other substances
that either kill or slow the growth of microbes.
• Antibiotics are molecules that kill or stop the growth of micro-organisms
including both bacteria and fungi.
MECHANISM OF
ANTIBIOTICS:
INHIBITION OF BACTERIAL CELL WALL
SYNTHESIS
(e.g. PENICILIN, AZTRENAM, VANCOMYCIN)
INHIBITION OF BACTERIAL PROTEIN
SYNTHESIS
(e.g.
MACROLIDES,AMINOGLUCOSIDASE,CHLORAMPHENICOL)
INHIBITION OF BACTERIAL FOLIC ACID
SYNTHESIS
(e.g.. PYRIMETHAMINE, SULFONAMIDES, TRIMETHOPRIN)
INHIBITION OF NUCLEIC ACID
SYNTHESIS
(e.g. .RIFAMPIN , FLUOROQUINOLONES)
MECHANISM OF
ACTION
ANTIBIOTIC RESISTANCE
Antibiotic resistance is when a microbe evolves to become more
or fully resistant to antibiotics which previously could treat it. It
is a specific type of drug resistance.
This mechanism of resistance might happen in several ways:
 micro-organisms can neutralize the antibiotic before it has an
effect
 micro-organisms may be able to pump the antibiotic out
 micro-organisms may be able to change the site (receptor)
where the antibiotic normally works
 micro-organisms can mutate and transfer genetic material
that codes for resistance to other micro-organisms
TIMELINE OF ANTIBIOTIC RESISTANCE
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998
S.pneumo.withReduced
SusceptibilitytoFluoroquinolones(%)
0
1
2
3
4
5
6
#ofPrescriptions/100Persons
15 - 64 y.o
> 64 y.o
# of Rx/100 persons
RELATIONSHIP OF RESISTANCE TO
ANTIBIOTIC USE
Decreased susceptibility of S. pneumoniae to
fluoroquinolones(FQRSP) in Canada
1.A man with chronic
lymphocytic leukemia admitted
with sudden onset high fever,
rigors chest pain and productive
cough.
2.Physical exam and chest x-ray
confirmed pneumonia &
azithromycin was prescribed
3.Gram stain showed numerous
neutrophils and sheets of lancet
shaped gram positive diplococci.
4.After 48 hours the patient
developed progressive
respiratory tract failure
ILLUSTRATIVE
CASE
DEVELOPMENT OF NEW ANTI-
MICROBIAL AGENTS
A.PHAGE THERAPY
B.BACTERIOCINS
C.EFFLUX PUMP INHIBITORS
D.NATURAL ANTI-MICROBIAL AGENTS
AS FOOD PRESERVATIVES
A. PHAGE
THERAPY• The discovery of bacteriophages (It is a virus that infects and
replicates within a bacterium) was reported by Frederick Twort in
1915 and Felix d'Hérelle in 1917.
• Phage therapy or viral phage therapy is the therapeutic use of
bacteriophages to treat pathogenic bacterial infections.CONVENTIONAL
ANTIBIOTICS
PHAGE THERAPY
THERAPEUTI
C INDEX
LOW HIGH
DOSES HIGH LOW (phages
replicate in vivo,
a smaller
effective dose
can be used)
EFFECT KILLS BOTH
HARMFUL AND
USEFUL BACTERIA
HARMLESS TO
HOST ORGANISM
AND FLORA
ANTIBACTER
IAL
---- EASIER TO
OVERCOME (Just
• Phages tend to be more
successful than
antibiotics where there
is a biofilm covered by a
polysaccharide layer,
which antibiotics
typically cannot
penetrate.
• In the West, no
therapies are currently
authorized for use on
humans, although
B. BACTERIOCINS
• Bacteriocins are a kind of ribosomal synthesized antimicrobial peptides
produced by bacteria, which can kill or inhibit bacterial strains closely-
related or non-related to produced bacteria, but will not harm the bacteria
themselves by specific immunity proteins. Bacteriocins are generally heat
tolerant.
• Unlike most antibiotics, which are secondary metabolites, bacteriocins are
ribosomally synthesized and sensitive to proteases while generally
harmless to the human body and surrounding environment.
• Bacteriocins are now widely used in food science to extend food
preservation duration (Ghrairi et al., 2012), Bacteriocins, such as nisin
(has GRAS status), promise safe use as a food preservative in vegetables,
dairy, cheese, meats, and other food products, as they inhibit
microorganisms contamination during the production process.
ADVANTAGE OF BACTERIOCIN OVER CONVENTIONAL ANTIBIOTICS
• These toxins target a minute fraction of a microbial community, the
selection for mutations that confer resistance is not taking place in multiple
species simultaneously, as is the case with broad-spectrum antibiotics.
C.EFFLUX PUMP
INHIBITORS• Pseudomonas aeruginosa is an opportunistic human pathogen.
The difficulty in treatment of pseudomonas infections arises
from being multidrug resistant (MDR) and exhibits resistance to
most antimicrobial agents due to the expression of different
mechanisms .
• Efflux pump plays an very important role in extruding the
antibiotics outside the bacterial cells providing a protective
means against their antibacterial activity.
• These pumps can extrude biocides, detergents, and other
metabolic inhibitors.
• Peptidomimetic compounds such as phenylalanine arginyl β-
naphthylamide (PAβN) have been introduced as efflux pump
inhibitors (EPIs); their mechanism of action is through
competitive inhibition with antibiotics on the efflux pump
resulting in increased intracellular concentration of antibiotic,
D.NATURAL ANTI-MICROBIAL AGENTS AS FOOD
PRESERVATIVES
Natural substances with antimicrobial action have been
identified from a very wide range of sources, including herbs
and other edible and medicinal plants, microorganisms and
animals. Many of these have been investigated, but few have
yet been exploited as food preservatives on a commercial
basis. Some examples are given below.HERBS AND OTHER
PLANTS WITH
ANTIMICROBIAL
ACTIVITY
ANTIMICROBIALS
FROM MICRO
ORGANISM
ANTIMICROBIAL
S FROM
ANIMALS
Cinnamon,clove,gr
een tea,garlic,
Natamycin,
nisin, lactacin
Chitosan,
lysozyme
The use of natural antimicrobial compounds in food has gained much
attention by the consumers and the food industry.
• The misuse and mishandling of antibiotics has resulted in the
dramatic rise of a group of microorganisms including foodborne
pathogens that are not only antibiotic resistant but also more
tolerant to several food processing and preservation methods This
has prompted the food industry to look for alternative
preservatives that can enhance the safety and quality of foods.
CONCLUS
IONInappropriate and excessive use of antibiotics is a
major factor contributing to emerging antibiotic
resistance.
Determinants of resistance are selected by
antibiotic use.
Multiple mechanisms exist for bacteria to become
resistant to antibiotics.
Antibiotic resistance continues to emerge as a
serious threat to public health.
THANK
YOU

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development of antimicrobial agents which can overcome the antimicrobial resistance

  • 1. CONCEPT NOTES ON : “MICROORGANISMS ARE INCREASINGLY BECOMING RESISTANT TO CONVENTIONAL ANTIBIOTICS: DEVELOPMENT OF ANTIMICROBIAL AGENTS HAS BECOME AN EMERGENCY NEED” TEAM MEMBERS: ARIJIT GOSWAMI (UG-IV) PRITHA NAYAK (UG-IV) ROHIT HALDER (UG-IV) SOUVIK SIKDAR (UG-III) MOLLA SALAUDDIN (UG-III)
  • 2. WHAT IS ANTIBIOTICS & ANTIMICROBIALS AGENTS ? • Antimicrobial agent: A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes. • Antibiotics are molecules that kill or stop the growth of micro-organisms including both bacteria and fungi.
  • 3. MECHANISM OF ANTIBIOTICS: INHIBITION OF BACTERIAL CELL WALL SYNTHESIS (e.g. PENICILIN, AZTRENAM, VANCOMYCIN) INHIBITION OF BACTERIAL PROTEIN SYNTHESIS (e.g. MACROLIDES,AMINOGLUCOSIDASE,CHLORAMPHENICOL) INHIBITION OF BACTERIAL FOLIC ACID SYNTHESIS (e.g.. PYRIMETHAMINE, SULFONAMIDES, TRIMETHOPRIN) INHIBITION OF NUCLEIC ACID SYNTHESIS (e.g. .RIFAMPIN , FLUOROQUINOLONES) MECHANISM OF ACTION
  • 4. ANTIBIOTIC RESISTANCE Antibiotic resistance is when a microbe evolves to become more or fully resistant to antibiotics which previously could treat it. It is a specific type of drug resistance. This mechanism of resistance might happen in several ways:  micro-organisms can neutralize the antibiotic before it has an effect  micro-organisms may be able to pump the antibiotic out  micro-organisms may be able to change the site (receptor) where the antibiotic normally works  micro-organisms can mutate and transfer genetic material that codes for resistance to other micro-organisms
  • 6. 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 S.pneumo.withReduced SusceptibilitytoFluoroquinolones(%) 0 1 2 3 4 5 6 #ofPrescriptions/100Persons 15 - 64 y.o > 64 y.o # of Rx/100 persons RELATIONSHIP OF RESISTANCE TO ANTIBIOTIC USE Decreased susceptibility of S. pneumoniae to fluoroquinolones(FQRSP) in Canada 1.A man with chronic lymphocytic leukemia admitted with sudden onset high fever, rigors chest pain and productive cough. 2.Physical exam and chest x-ray confirmed pneumonia & azithromycin was prescribed 3.Gram stain showed numerous neutrophils and sheets of lancet shaped gram positive diplococci. 4.After 48 hours the patient developed progressive respiratory tract failure ILLUSTRATIVE CASE
  • 7. DEVELOPMENT OF NEW ANTI- MICROBIAL AGENTS A.PHAGE THERAPY B.BACTERIOCINS C.EFFLUX PUMP INHIBITORS D.NATURAL ANTI-MICROBIAL AGENTS AS FOOD PRESERVATIVES
  • 8. A. PHAGE THERAPY• The discovery of bacteriophages (It is a virus that infects and replicates within a bacterium) was reported by Frederick Twort in 1915 and Felix d'Hérelle in 1917. • Phage therapy or viral phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections.CONVENTIONAL ANTIBIOTICS PHAGE THERAPY THERAPEUTI C INDEX LOW HIGH DOSES HIGH LOW (phages replicate in vivo, a smaller effective dose can be used) EFFECT KILLS BOTH HARMFUL AND USEFUL BACTERIA HARMLESS TO HOST ORGANISM AND FLORA ANTIBACTER IAL ---- EASIER TO OVERCOME (Just • Phages tend to be more successful than antibiotics where there is a biofilm covered by a polysaccharide layer, which antibiotics typically cannot penetrate. • In the West, no therapies are currently authorized for use on humans, although
  • 9. B. BACTERIOCINS • Bacteriocins are a kind of ribosomal synthesized antimicrobial peptides produced by bacteria, which can kill or inhibit bacterial strains closely- related or non-related to produced bacteria, but will not harm the bacteria themselves by specific immunity proteins. Bacteriocins are generally heat tolerant. • Unlike most antibiotics, which are secondary metabolites, bacteriocins are ribosomally synthesized and sensitive to proteases while generally harmless to the human body and surrounding environment. • Bacteriocins are now widely used in food science to extend food preservation duration (Ghrairi et al., 2012), Bacteriocins, such as nisin (has GRAS status), promise safe use as a food preservative in vegetables, dairy, cheese, meats, and other food products, as they inhibit microorganisms contamination during the production process. ADVANTAGE OF BACTERIOCIN OVER CONVENTIONAL ANTIBIOTICS • These toxins target a minute fraction of a microbial community, the selection for mutations that confer resistance is not taking place in multiple species simultaneously, as is the case with broad-spectrum antibiotics.
  • 10. C.EFFLUX PUMP INHIBITORS• Pseudomonas aeruginosa is an opportunistic human pathogen. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms . • Efflux pump plays an very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. • These pumps can extrude biocides, detergents, and other metabolic inhibitors. • Peptidomimetic compounds such as phenylalanine arginyl β- naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic,
  • 11. D.NATURAL ANTI-MICROBIAL AGENTS AS FOOD PRESERVATIVES Natural substances with antimicrobial action have been identified from a very wide range of sources, including herbs and other edible and medicinal plants, microorganisms and animals. Many of these have been investigated, but few have yet been exploited as food preservatives on a commercial basis. Some examples are given below.HERBS AND OTHER PLANTS WITH ANTIMICROBIAL ACTIVITY ANTIMICROBIALS FROM MICRO ORGANISM ANTIMICROBIAL S FROM ANIMALS Cinnamon,clove,gr een tea,garlic, Natamycin, nisin, lactacin Chitosan, lysozyme The use of natural antimicrobial compounds in food has gained much attention by the consumers and the food industry. • The misuse and mishandling of antibiotics has resulted in the dramatic rise of a group of microorganisms including foodborne pathogens that are not only antibiotic resistant but also more tolerant to several food processing and preservation methods This has prompted the food industry to look for alternative preservatives that can enhance the safety and quality of foods.
  • 12. CONCLUS IONInappropriate and excessive use of antibiotics is a major factor contributing to emerging antibiotic resistance. Determinants of resistance are selected by antibiotic use. Multiple mechanisms exist for bacteria to become resistant to antibiotics. Antibiotic resistance continues to emerge as a serious threat to public health.