Pseudomonas aeruginosa an epitome of a drug resistance in bacteria Learning materials for undergraduate students

1. PSEUDOMONAS AERUGINOSAPSEUDOMONAS AERUGINOSA;;
AN EPITOME OF DRUGAN EPITOME OF DRUG
RESISTANCE IN BACTERIARESISTANCE IN BACTERIA
Seminar presentation
by
Bamidele Tolulope Odumosu, PhD

2. IntroductionIntroduction
Pseudomonas aeruginosa is a well known
nosocomial pathogen (hospital infection
causing bacteria) responsible for a wide
range of mild to severe infections.
This bacterium is naturally resistant to
many antimicrobial agents used in the
hospital because it has the distinctive
capacity via multiple mechanism to become
resistant to virtually all antibiotics available
commercially

3. Genus PseudomonasGenus Pseudomonas
Members of the genus Pseudomonas are rod
shaped, Gram-negative bacteria with one or
more polar flagella, aerobic, non-spore
forming and are catalase positive.
Members of this genus include Pseudomonas.
aeruginosa,
P. fluorescens, P. putida, P. polycolor and P.
syringae.

4. Pseudomonas. aeruginosaPseudomonas. aeruginosa
A typical P.
aeruginosa is
identified with the
following
biochemical
characteristics
Positive oxidase
reaction,
Negative for indole
production,
 Negative methyl red
reaction,

5. Characteristics contdCharacteristics contd
 Voges-proskauer test
is negative,
 Negative citrate
utilization
 Non-Lactose
fermenter
 beta hemolytic on
blood agar
 production of
pyoverdin and
pyocyanin

6. Pseudomonas aeruginosaPseudomonas aeruginosa as aas a
pathogenpathogen
This Gram-negative bacillus exists
everywhere in nature especially warm
moist environment, and can be frequently
isolated from soil, water, plants, sewage
and occasionally from the normal human
skin.
P. aeruginosa is a highly relevant
opportunistic bacterium that causes disease
in humans and plants

7. ……as a pathogen contdas a pathogen contd
According CDC ,Pseudomonas was named the
fifth most frequently isolated nosocomial
pathogen,
 The second leading cause of nosocomial
pneumonia,
The third most common agent of urinary tract
infection.
Fourth most frequently encountered pathogen in
surgical site infections.
And the seventh most implicated leading cause of
bloodstream infections

8. ……as a pathogen contdas a pathogen contd
And According to report from Pier et al.
(2004), P. aeruginosa is responsible for a
number of clinical conditions, namely
endocarditis, otitis, urinary tract infections,
bone and joints infection, central nervous
system infection, respiratory infections,
gastrointestinal infections, skin and soft skin
infections including wounds, bacteremia,
keratitis, neonatal opthalmia, folliculitis and
unmanageable forms of acne vulgaris

9. AdaptabilityAdaptability
Its ability to survive harsh conditions such
as high temperature of 42o
C
Its minimal nutrient requirement and
oxygen usage makes it easier to persist and
colonize many artificial and natural
habitats
Its ubiquitousness in and around the
hospitals and the community
Its efficient opportunistic abilities as a
pathogen

10. PathogenicityPathogenicity
Is largely influenced by multiple bacterial
virulencefactors .
 They aid its colonization and invasion and its
genetic flexibility enabling it to survive in varied
environments
Colonization is due to multiple factors including
fimbriae or pili, flagella, and surface
polysaccharides that enable its adherence to
epithelium tissues
While its tissue invasion is by the production of
elastase, alkaline proteases, hemolysins etc

11. Pathogenicity contd.Pathogenicity contd.
Pseudomonas aeruginosa, is capable of
Biofilm formation under favourable nutrient
and environmental condition which allows;
The pathogen to becomes resistant to
antibiotics during an active infective stage
It also protects it from desiccation
Enhances its cell-to-cell communication
Increases its plasmid stability and genetic
exchange as well as
Decreases its susceptibility to killing by host
defense mechanisms

12. Antibiotic resistance inAntibiotic resistance in
Pseudomonas aeruginosaPseudomonas aeruginosa
Inherent trait (intrinsic or
natural ability) This is related
to its genetic background
Acquired trait (extrinsic). This
is related to its environmental
relationship

13. Inherent or Natural AbilitiesInherent or Natural Abilities
This often involves the following;
Low affinity for targets cells
Low cell permeability
Active efflux pump systems
Presence of chromosomal AmpC β-
lactamase also known as
cephalosporinase

14. Bacteria Outer MembraneBacteria Outer Membrane

15. Bacteria Outer MembraneBacteria Outer Membrane
P. aeruginosa is intrinsically
resistant to a number of
structurally unrelated antibiotics
due to low permeability of its outer
membrane which is 1/100 of the
permeability of E. Coli outer
membrane

16. Mechanisms of Resistance: EffluxMechanisms of Resistance: Efflux
 Active, energy dependent pumps cause efflux of drugs
Bacterial Cytosol
PG layer
Outer membrane
drug
Efflux pump

17. Mechanisms of Resistance: EffluxMechanisms of Resistance: Efflux
 Active, energy dependent pumps can also cause
efflux of drugs

18. Acquired resistanceAcquired resistance
Acquired resistance in bacteria is a
modification of existing genetic
material or acquisition of new gene
that makes them to be resistant to
drugs that they were previously
susceptible.

19. Acquired resistanceAcquired resistance
This occurs by Mutation of its own
DNA and its transfer to progeny during
DNA replication also known as
vertical gene transfer or
By horizontal gene transfer i.e.
importation of resistance genes from
other sources such as bacteria

20. Acquired resistanceAcquired resistance
Vertical gene transfer or vertical
evolution are mutations in P.
aeruginosa as well as other
microorganisms which are
transferred to progeny during
DNA replication. They are
spontaneous event hence cannot
be predicted.

21. Acquired resistanceAcquired resistance
While lateral or horizontal gene
transfer is the acquisition of genetic
materials such as plasmid, integrons
and other mobile genetic element
containing resistant genes from other
bacteria in the environment. This is
the most common method by which
most bacteria as well as P.
aeruginosa acquires resistant genes

22. Acquired resistanceAcquired resistance
Acquired resistance genes in P.
aeruginosa among many other functions
is the presence of plasmids which allows
for the production of β-lactamases and
extended-spectrum β-lactamases (ESBL)
enzymes that hydrolyses beta-lactam
antibiotics such as the penicillins,
cephalosporins and monobactams.

23. Enzymatic degradation of ESBLs:Enzymatic degradation of ESBLs:
Mechanisms ofMechanisms of ββ-lactamase-lactamase
N
O
N
O
OH
S CH3
CH3
O
R
H
β-lactamase
CH2
OH
β-lactamase
CH2
OH
N
O
N
O
OH
S CH3
CH3
O
R
H
β-lactamase
CH2
O
H H2O
N
O
N
O
OH
S CH3
CH3
O
R
H
H
OH
β-lactamase
CH2
OH
+
Hydrolysis of Oxyimino group
Penicillin drug
Inactivated drug

25. Conclusion.Conclusion.
Pseudomonas aeruginosa possess
arsenal of resistance genes and also has
the ability to acquire more from other
resistant bacteria such as Acinetobacter
baumannii, Escherichia coli, Klebsiella
pneumoniae.
This ability and nature will continue
make P. aeruginosa a very important
bacteria in the hall of resistance.