Pseudomonas aeruginosa establishes itself in the lungs of cystic fibrosis patients and uses quorum sensing to coordinate biofilm formation. Quorum sensing involves the production and detection of signaling molecules called homoserine lactones, which trigger biofilm formation and virulence factor production above a threshold concentration. Detecting these signaling molecules can indicate the presence of P. aeruginosa biofilms early on. Inhibiting quorum sensing is a promising approach for novel cystic fibrosis therapies, as it may prevent biofilm formation and make bacteria more susceptible to antibiotics.

1. SONAL RAWAT
A0989216038Sonal Rawat
BSc(H) Microbiology
Sem-6 Section- B
A0989216038
Quorum Sensing an approach in
detection of Pseudomonas aeruginosa
biofilms in cystic fibrosis

2. Cystic fibrosis and Pseudomonas
aeruginosa
• Cystic fibrosis is a hereditary disorder that affects the exocrine glands
like sweat glands and mucosal glands of patients.
• The CF gene encodes a protein known as cystic fibrosis trans
membrane conductance regulator (CFTR). Mutation of this gene
makes the CFTR protein dysfunctional which acts as channel for large
mucus production.
• These mucoid secretions clog airways and reduces mucocilliary
clearance of inhaled microbes and leads to the formation of bacterial
biofilms with mucoid layers as their habitat. Pseudomonas
aeruginosa an opportunistic pathogen establishes itself inside the
airways of the patients and colonizes there permanently.

3. Quorum sensing mechanism
• Quorum sensing is a term that describes an environmental sensing system
that allows bacteria to monitor their own population density which
contributes significantly to the size and development of bio film.
• Pseudomonas aeruginosa produce and release the signaling molecules
which are known homoserine lactones (HSLs).
• After attainment of a threshold concentration these become detectable to
bacteria populations, which interact with cognate receptors to induce the
transcriptional expression of various target genes including those
encoding production of virulence factors, horizontal gene transfer, biofilm
formation etc.
• The HSLs can be detected via spectroscopy in the sputum sample which
indicates the presence of bacterial colonies of Pseudomonas aeruginosa
and early formation of biofilms.

4. Pseudomonas
aeruginosa comprises of
two AHL‐based QS
systems; Las and Rhl.
• The Las system has the
transcriptional regulator
LasR and its cognate AHL
signal, N‐(3‐oxododecano
yl)‐L‐homoserine lactone
(3‐0X0‐C12‐ HSL),
synthesized by the AHL
synthase LasI
• Similarly, the Rhl system
is comprised of RhlR
together with its cognate
AHL, N‐butyryl‐L‐homose
rine lactone (C4‐HSL),
synthesized by the RhlI
AHL synthase .

5. QS and biofilm formation
• Biofilms are communities of microorganisms that gets
attached to an inert or living surface by a self produced
polymeric substance (EPS)
• Biofilm formation is an important feature of
Pseudomonas aeruginosa pathogenicity and
contributes significantly to the resistance of bacteria to
aggressive antimicrobial therapy.
• Three independent studies have shown that
the P.aeruginosa genome is subject to AHL‐dependent
regulation .In reports the Las QS system was found to
be essential for creation of mature, differentiated
biofilms

6. • In a flow‐chamber set‐up, stalk‐like structures with
intervening water channels composed the PA01 biofilm.
In sharp contrast, the las1‐ biofilm was flat and
undifferentiated.
• Upon exposure to the detergent sodium dodecyl sulfate
(SDS), the las1‐ biofilm quickly dispersed from the
substratum, whereas the wild‐type biofilm remained
intact. So in addition to being structurally altered, the
mutant biofilm was functionally impaired in its ability to
resist biocidal agents.
• Since this inaugural report, several groups have
published findings supporting a role for QS, system,
in P.aeruginosa biofilm formation.

7. QS System in novel drugs and
therapeutics
• Signal molecules aid in biofilm formation which in turn confer various
properties of pathogenicity to the clinical isolates including drug
resistance. The use of quorum sensing signal blockers to attenuate
bacterial pathogenicty is therefore highly attractive, particularly with
respect to the emergence of multi antibiotic resistant bacteria.
AGENT COMMENTS
Macrolides Inhibition of QS regulated factors: inhibition
of alginate production
Garlic QS is inhibited by garlic and renders P
aeruginosa more sensitive to tobramycin
and host defences
Synthetic analogues Synthetic autoinducer analogues/ ligands;
inhibition of QS regulated factors and
biofilm formation.
Plant extracts Inhibition of LaA protease, LasB elastase,
and biofilm formation by several different
plant extracts.
QS Vaccine Specific antibody to 3-oxo-C-12-HSL plays a
protective role in infection

8. Conclusion
• QS plays an important role in maintaining the cell density
of population of bacteria.
• It allows signalling molecules to produce virulence
factors which help in biofilm formation.
• These signaling molecules and their metabolites can be
identified via spectroscopy.
• Early detection of Pseudomonas aeruginosa via quorum
sensing can help in prevention of bio film by inhibiting the
signaling AHL molecules.
• Due to inhibition of biofilm formation aggressive
antibiotic therapies can be applied to eliminate the
infection.