AS MICROORGANISIMS ARE INCREASINGLY BECOMING RESISTANT TO CONVENTIONAL ANTIBIOTICS,SO THERE IS ANEED OF NEW ANTIMICROBIAL AGENTS WHICH CAN OVERCOME THE RESISTANCE AND HELPS IN REDUCING THE OVERUSE AND MISHANDLING OF ANTIBIOTICS
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.