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PSEUDOMONAS AERUGINOSAPSEUDOMONAS AERUGINOSA; ; AN EPITOME OF DRUG AN EPITOME OF DRUG
RESISTANCE IN BACTERIARESISTANCE IN BACTERIA
Seminar presentation by
Bamidele Tolulope Odumosu, PhD
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
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.
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,
Characteristics contdCharacteristics contd Voges-proskauer test is
negative, Negative citrate
utilization Non-Lactose fermenter beta hemolytic on blood
agar production of pyoverdin
and pyocyanin
Pseudomonas aeruginosa Pseudomonas aeruginosa as a as 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
……as a pathogen contdas a pathogen contdAccording 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
……as a pathogen contdas a pathogen contdAnd 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
AdaptabilityAdaptabilityIts ability to survive harsh conditions such
as high temperature of 42oCIts 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
PathogenicityPathogenicityIs largely influenced by multiple bacterial virulence
factors . They aid its colonization and invasion and its
genetic flexibility enabling it to survive in varied
environmentsColonization 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
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 desiccationEnhances its cell-to-cell communicationIncreases its plasmid stability and genetic
exchange as well asDecreases its susceptibility to killing by host
defense mechanisms
Antibiotic resistance in Antibiotic 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
Inherent or Natural AbilitiesInherent or Natural AbilitiesThis often involves the following;Low affinity for targets cellsLow cell permeabilityActive efflux pump systemsPresence of chromosomal AmpC β-
lactamase also known as cephalosporinase
Bacteria Outer MembraneBacteria Outer Membrane
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
Mechanisms of Resistance: EffluxMechanisms of Resistance: Efflux
Active, energy dependent pumps cause efflux of drugs
Bacterial Cytosol
PG layer
Outer membrane
drug
Efflux pump
Mechanisms of Resistance: EffluxMechanisms of Resistance: Efflux Active, energy dependent pumps can also cause efflux of
drugs
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.
Acquired resistanceAcquired resistanceThis 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
Acquired resistanceAcquired resistanceVertical 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.
Acquired resistanceAcquired resistanceWhile 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
Acquired resistanceAcquired resistanceAcquired 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.
Enzymatic degradation of ESBLs:Enzymatic degradation of ESBLs: Mechanisms of Mechanisms of -lactamase-lactamase
N
ON
O
OH
S CH3
CH3O
RH
-lactamase
CH2
OH-lactamase
CH2
OH
N
ON
O
OH
S CH3
CH3O
RH
-lactamase
CH2
OH H2O
N
ON
O
OH
S CH3
CH3O
RH
HOH
-lactamase
CH2
OH
+Hydrolysis of Oxyimino group
Penicillin drug
Inactivated drug
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.