SEMOLECULAR MECHANISMS OF ANTIMICROBIAL RESISTANCE IN BACTERIA

BYMOTUMA DEBELO

(5th YEAR)

 

A SEMINAR PAPER PERESENTED FOR THE COURSE ON ANIMAL HEALTH  

(BMSC 502) 

ADDIS ABABA UNIVERSITY COLLEGE OF VETERINARY MEDICINE AND

AGRICULTUREDEPARTMENT OF BIOMEDICAL SCIENCE

MARCH, 20/2014BISHOFTU, ETHIOPIA

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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

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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.

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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

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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;

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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

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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.

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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 

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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

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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.

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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

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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

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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

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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

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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

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CONT……

Antimicrobial resistance traits are genetically coded, and can either be intrinsic or acquired.

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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).

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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.

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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.

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I G

USS THAT IS IT THANK

YOU