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MOLECULAR MECHANISMS OFANTIMICROBIAL RESISTANCE IN BACTERIA
BY
MOTUMA DEBELO
(5th YEAR)
A SEMINAR PAPER PERESENTED FOR THE COURSE ON ANIMAL HEALTH
(BMSC 502)
ADDIS ABABA UNIVERSITY
COLLEGE OF VETERINARY MEDICINE AND
AGRICULTURE
DEPARTMENT OF BIOMEDICAL SCIENCE
MARCH, 20/2014
BISHOFTU, ETHIOPIA
1
1.INTRODUCTION
Microbes are living organisms
They include bacteria,virus and others
Some microbes cause disease
Microorganisms to servive they should tolerate or disrupt
mech of actn of antimicrbls through differ ways
Antimicrobials used in animals and agriculture lead to spread
of resistant strain to human population
2
CONT……
Since there is no work done on molecular mechanisms of
antimicrobial resistance in bacteria in Ethiopia
by studying this mechanism of resistance I want to rectify
antibiotic wide reaction problems or
I want to complete picturing of the problem as society
are becoming aware of the resistance and raise up to
combat infectious disease.
3
CONT…..
Therefore, the objectives of my seminar paper are;
to highlight the aspects of antimicrobial resistance
through a discussion of:
Bacterial strategies involved in resisting
antimicrobial actions and
The molecular basis for bacterial resistance to
antimicrobial actions
4
2. MOLECULAR MECHANISMS OF ANTIMICROBIAL RESISTANCE IN BACTERIA
To realize it requires,
understanding of bacterial structure and function
Antibiotics selectively kill bacteria because of
Structural and metabolic differ
gram –ve bacteria have;
5
COTN…..
Gram +ve bacteria have no
CONT…
The major problem of the emergence of resistant
bacteria are due to:
misuse and overuse of antibiotics
antimicrobial sold over the country without prescription
Inappropriate prescription and treatment
before laboratory investigations
7
3. TYPES OF MOLECULAR MECHANISMS OF RESISTANCE
There are two types of mol mech of bacterial
resistance.
3.1. INTRINSIC RESISTANCE (INSENSITIVITY)
Is absence of cellular antibiotic susceptibility e.g mycoplasm is resistant
to penicillin b/c it lack cell wall
In this type, microbes are resistant through their inherent structure or
functional characteristics
Natural insensitivity can be due to;
* lack of affinity of the drug for the bacterial target
* inaccessibility of the drug into the bacterial cell
* extrusion of the drug
* innate production of enzymes that inactivate the drug.
8
EXAMPLES OF INTRINSIC RESISTANCE AND THEIR RESPECTIVE MECHANISMS
Organisms Natural resistance
against:
Mechanism of resistance
Gram-positive bacteria Aztreonam (a beta-lactam they lack penicillin binding
proteins (PBPs)
Gram-negative bacteria Vancomycin they lack to uptake it b/c
may be their atomic differ or
lack porin channel
Klebsiella spp Ampicillin (a beta-lactam beta-lactamases producn
that destroy ampicillin
before the drug can reach
the PBP targets
3.2. ACQUIRED RESISTANCE
Said to occur when previously susceptible microbes
become resistant
plasmid mediated resistance tend to encode
synthesis of enzymes that modify antibiotics
plasmid reproduce it
self within a cell and spread to other cells by
10
CONT…
4. BACTERIAL RESISTANCE STRATEGIES
To survive, bacteria able to disrupt essential steps required for the
effective action of antimicrobial agent
Intended modes of action of antmcrbls are counter-acted via
four main strategies.
4.1) Reducing entry (permeability) of antimicrobial agents
impermeability of antimicrobial is inability to gain entry into site of drug target
the way which antibiotics cross bacterial
outer m/m is through porin channels but
some bacteria e.g Gram –ve are modfy cell
m/m porin channel’s; *frequency and reduce
* size entry of ant
* selectivity
12
4.2, EXPULSION (PUMPING OUT) OF ANTIMICROBIAL AGENTS
To be effective antimicr must present at a sufficient high [ ]
within the cell
Some bacteria posses membrane protein that
act as; export (efflux pump) that extrude antibiotic
out of the cell
as the reasult microbes cause
low intracellular [ ] of antimicrobial agent
and detoririet effect of the drug by diluting.
13
4.3. INACTIVATION OF ANTIMICROBIAL AGENTS
Microbes preserve themselves by destroying the
active component of antimicrobial agent
Mechanisms of rendering antmicrbl inactive is
by enzymatic hydrolysis of antibiotics
4.4. MODIFICATION OF ANTIMICROBIAL TARGETS
= resistant bacteria envade antimicrobials by
reprogramming the target site to avod recog
camouflaging
and
this reasul, inspite of presence of intact
and active antimicrobial agent
No binding so
No inhibition will take place
15
5. MECHANISMS OF REGULATION OF ANTIMICROBIAL RESISTANCE
To prevent and control drug-resistant infections;
promote appropriate drug-use policies
* This is implemented
through a public health education on appropriate antimicr
obial drug use and prevention of GPA therapy for
humans and animals
Improved diagnostic practices, this is held
by encouraging rapid diagnosis to
guide drug prescribing
16
CONT….
the other way of regulating antimicrobial resist
using Probiotics instead of antibiotics
* used to fight against
bacteria/pathogens
their MOA is not yet understood however few
mechanisms deduced bellow:
* exclude micrbs by competing for nutrients
* block the ligand-receptor contact
* mimic the oligosaccharide receptors
of the host cells used by pathogens to enter the
cells
17
cont…
Phytochemicals:
* plant chemicals that are neither vitamins nor minrls
* have health-enhancing effects
Vaccination: is part of prophylaxis and it is any measures
taken to prevent illness before it occurs.
* its basis is to produce Ab quickly and in greater
number
18
6. CONCLUSION AND RECOMMENDATIONS
Antimicrobial resistance is the ability of a microorgan
ism to survive and multiply in the
presence of an antimicrobial agent that would normally
kill this species of microorganism.
Bacteria are able to resist the effects of antimicrobials
through preventing intracellular access and immediately
removing antimicrobial substances through efflux pumps
19
CONT……
Antimicrobial resistance
traits are genetically coded,
and can either be intrinsic or
acquired.
20
The prevention and control of drug-resistant
infections requires measures to promote the
appropriate use of antimicrobial drugs and
prevent the transmission of infections (whether
drug-resistant or not).
21
BASED ON THESE FACTS THE FOLLOWING RECOMMENDATIONS ARE
PIN POINTED:
A wide scale Research should have to be initiated
and encourage in the surveillance and control of
molecular mechanisms of antimicrobial drug
resistance.
All methods of antimicrobial resistance control such
as appropriate drug use policies, reducing rate of
infection transmission, improved diagnostic practice,
vaccines, probiotics, phytochemicals should
integrated and implemented with the underlying
aim of reducing goal of preserve effective of
antimicrobials.
22
Periodic testing of drug efficacy; farms should be re
gularly monitored for antimicrobial resistance.
Public awareness creation about the problems of
antimicrobial resistance via continuous teaching farmers and
the society as the whole by veterinary extension service is
very mandatory.
23
Molecular mechanisms of antimicrobial resistance in bacteria

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Molecular mechanisms of antimicrobial resistance in bacteria

  • 1. SE MOLECULAR MECHANISMS OFANTIMICROBIAL RESISTANCE IN BACTERIA BY MOTUMA DEBELO (5th YEAR) A SEMINAR PAPER PERESENTED FOR THE COURSE ON ANIMAL HEALTH (BMSC 502) ADDIS ABABA UNIVERSITY COLLEGE OF VETERINARY MEDICINE AND AGRICULTURE DEPARTMENT OF BIOMEDICAL SCIENCE MARCH, 20/2014 BISHOFTU, ETHIOPIA 1
  • 2. 1.INTRODUCTION Microbes are living organisms They include bacteria,virus and others Some microbes cause disease Microorganisms to servive they should tolerate or disrupt mech of actn of antimicrbls through differ ways Antimicrobials used in animals and agriculture lead to spread of resistant strain to human population 2
  • 3. CONT…… Since there is no work done on molecular mechanisms of antimicrobial resistance in bacteria in Ethiopia by studying this mechanism of resistance I want to rectify antibiotic wide reaction problems or I want to complete picturing of the problem as society are becoming aware of the resistance and raise up to combat infectious disease. 3
  • 4. CONT….. Therefore, the objectives of my seminar paper are; to highlight the aspects of antimicrobial resistance through a discussion of: Bacterial strategies involved in resisting antimicrobial actions and The molecular basis for bacterial resistance to antimicrobial actions 4
  • 5. 2. MOLECULAR MECHANISMS OF ANTIMICROBIAL RESISTANCE IN BACTERIA To realize it requires, understanding of bacterial structure and function Antibiotics selectively kill bacteria because of Structural and metabolic differ gram –ve bacteria have; 5
  • 7. CONT… The major problem of the emergence of resistant bacteria are due to: misuse and overuse of antibiotics antimicrobial sold over the country without prescription Inappropriate prescription and treatment before laboratory investigations 7
  • 8. 3. TYPES OF MOLECULAR MECHANISMS OF RESISTANCE There are two types of mol mech of bacterial resistance. 3.1. INTRINSIC RESISTANCE (INSENSITIVITY) Is absence of cellular antibiotic susceptibility e.g mycoplasm is resistant to penicillin b/c it lack cell wall In this type, microbes are resistant through their inherent structure or functional characteristics Natural insensitivity can be due to; * lack of affinity of the drug for the bacterial target * inaccessibility of the drug into the bacterial cell * extrusion of the drug * innate production of enzymes that inactivate the drug. 8
  • 9. EXAMPLES OF INTRINSIC RESISTANCE AND THEIR RESPECTIVE MECHANISMS Organisms Natural resistance against: Mechanism of resistance Gram-positive bacteria Aztreonam (a beta-lactam they lack penicillin binding proteins (PBPs) Gram-negative bacteria Vancomycin they lack to uptake it b/c may be their atomic differ or lack porin channel Klebsiella spp Ampicillin (a beta-lactam beta-lactamases producn that destroy ampicillin before the drug can reach the PBP targets
  • 10. 3.2. ACQUIRED RESISTANCE Said to occur when previously susceptible microbes become resistant plasmid mediated resistance tend to encode synthesis of enzymes that modify antibiotics plasmid reproduce it self within a cell and spread to other cells by 10
  • 12. 4. BACTERIAL RESISTANCE STRATEGIES To survive, bacteria able to disrupt essential steps required for the effective action of antimicrobial agent Intended modes of action of antmcrbls are counter-acted via four main strategies. 4.1) Reducing entry (permeability) of antimicrobial agents impermeability of antimicrobial is inability to gain entry into site of drug target the way which antibiotics cross bacterial outer m/m is through porin channels but some bacteria e.g Gram –ve are modfy cell m/m porin channel’s; *frequency and reduce * size entry of ant * selectivity 12
  • 13. 4.2, EXPULSION (PUMPING OUT) OF ANTIMICROBIAL AGENTS To be effective antimicr must present at a sufficient high [ ] within the cell Some bacteria posses membrane protein that act as; export (efflux pump) that extrude antibiotic out of the cell as the reasult microbes cause low intracellular [ ] of antimicrobial agent and detoririet effect of the drug by diluting. 13
  • 14. 4.3. INACTIVATION OF ANTIMICROBIAL AGENTS Microbes preserve themselves by destroying the active component of antimicrobial agent Mechanisms of rendering antmicrbl inactive is by enzymatic hydrolysis of antibiotics
  • 15. 4.4. MODIFICATION OF ANTIMICROBIAL TARGETS = resistant bacteria envade antimicrobials by reprogramming the target site to avod recog camouflaging and this reasul, inspite of presence of intact and active antimicrobial agent No binding so No inhibition will take place 15
  • 16. 5. MECHANISMS OF REGULATION OF ANTIMICROBIAL RESISTANCE To prevent and control drug-resistant infections; promote appropriate drug-use policies * This is implemented through a public health education on appropriate antimicr obial drug use and prevention of GPA therapy for humans and animals Improved diagnostic practices, this is held by encouraging rapid diagnosis to guide drug prescribing 16
  • 17. CONT…. the other way of regulating antimicrobial resist using Probiotics instead of antibiotics * used to fight against bacteria/pathogens their MOA is not yet understood however few mechanisms deduced bellow: * exclude micrbs by competing for nutrients * block the ligand-receptor contact * mimic the oligosaccharide receptors of the host cells used by pathogens to enter the cells 17
  • 18. cont… Phytochemicals: * plant chemicals that are neither vitamins nor minrls * have health-enhancing effects Vaccination: is part of prophylaxis and it is any measures taken to prevent illness before it occurs. * its basis is to produce Ab quickly and in greater number 18
  • 19. 6. CONCLUSION AND RECOMMENDATIONS Antimicrobial resistance is the ability of a microorgan ism to survive and multiply in the presence of an antimicrobial agent that would normally kill this species of microorganism. Bacteria are able to resist the effects of antimicrobials through preventing intracellular access and immediately removing antimicrobial substances through efflux pumps 19
  • 20. CONT…… Antimicrobial resistance traits are genetically coded, and can either be intrinsic or acquired. 20
  • 21. The prevention and control of drug-resistant infections requires measures to promote the appropriate use of antimicrobial drugs and prevent the transmission of infections (whether drug-resistant or not). 21
  • 22. BASED ON THESE FACTS THE FOLLOWING RECOMMENDATIONS ARE PIN POINTED: A wide scale Research should have to be initiated and encourage in the surveillance and control of molecular mechanisms of antimicrobial drug resistance. All methods of antimicrobial resistance control such as appropriate drug use policies, reducing rate of infection transmission, improved diagnostic practice, vaccines, probiotics, phytochemicals should integrated and implemented with the underlying aim of reducing goal of preserve effective of antimicrobials. 22
  • 23. Periodic testing of drug efficacy; farms should be re gularly monitored for antimicrobial resistance. Public awareness creation about the problems of antimicrobial resistance via continuous teaching farmers and the society as the whole by veterinary extension service is very mandatory. 23