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system has sensed that there is enough number of bacteria in population that is beneficial and/or “safe” to initiate that genetic activity, they activate certain genes only.
This population density dependent phenomenon is called quorum sensing. Quorum
sensing was first observed as a function of cell density dependent light produced by
marine bacterium Vibrio fischeri (Bassler et al. 1993; Mukherjee and Bassler 2019).
Broadly, three categories of quorum sensing have been identified: a) found in
Gram negative bacteria, comprising LuxI/LuxR type quorum sensing use acylhomoserine lactone (AHL) as signal molecules; b) peptide based signaling system
in Gram positive bacteria; and c) LuxS-encoded autoinducer-2 (AI-2), which is utilized by both Gram negative as well as Gram positive bacteria (Saxena et al. 2019;
Liu et al. 2018). The AHL signaling molecules are biosynthesized by LuxI protein
and are capable of diffusing across cell membrane. With an increase in cell density,
AHL are recognized by transcriptional regulator protein LuxR. This LuxR-AHL
complex triggers transcription of several genes and play an important role in biofilm
maturation. In P. aeruginosa, LasR-30C12-HSL complex differentially activates
several genes in concentration dependent manner. P. aeruginosa LasI mutants have
impaired 30C12-Homo Serien Lactone (HSL) synthesis and subsequently affected
biofilm maturation. Adding LasI generated 30C12-HSL quorum sensing signal
could restore the biofilm architecture (Parsek and Greenberg 2000). Unlike Gram
negative bacterial species, Gram positive species utilize peptides of varying length
(5 to 87 amino acids) as quorum sensing signal molecules. S. pneumoniae utilizes a
17-residue competence stimulating peptide (CSP) quorum sensing and S. mutans
uses 21 a/a CSP quorum sensing to induce genetic competence during promoted
biofilm growth (Okada et al. 2005). Bacillus subtilis and Staphylococcus aureus
have Ser/Thr kinases mediated regulation of biofilm growth. PrkC is a dimeric Ser/
Thr kinase like auto phosphorylating protein found in B. subtilis cell membrane that
also phosphorylates external myelin basic protein (MBP). S. aureus has Ser/Thr
kinase like Stk1 protein that phosphoryltes LuxS protein to eliminate production of
AI-2, thereby causing biofilm formation (Cluzel et al. 2010).
7.4 Biofilm Associated Multidrug Resistance
Numerous research studies have reported the high drug tolerance of bacteria in biofilms. Multi cellularity of biofilms confers protection to these cells. This tolerance
is due to the intrinsic genetic drift from the free floating lifestyle to surface adhered
forms (Romeo 2008; Sánchez et al. 2019). There are several hypothesis given to
explain the high recalcitrance in biofilm bacteria such as development of concentration gradient of substrates create localized microenvironments, effective management of stress response within biofilms in certain bacterial cells, slowed or blocked
penetration of antimicrobials in biofilms due to extracellular matrix, biofilms act as
a reservoir of persisters. In planktonic state, there is excess of nutrients that bacteria
can utilize but is unable to deplete substrates from the neighbouring cells due to not
enough metabolic activity (Donlan 2002). On other hand, coordinated and
B. P. Singh et al.
system has sensed that there is enough number of bacteria in population that is beneficial and/or “safe” to initiate that genetic activity, they activate certain genes only.
This population density dependent phenomenon is called quorum sensing. Quorum
sensing was first observed as a function of cell density dependent light produced by
marine bacterium Vibrio fischeri (Bassler et al. 1993; Mukherjee and Bassler 2019).
Broadly, three categories of quorum sensing have been identified: a) found in
Gram negative bacteria, comprising LuxI/LuxR type quorum sensing use acylhomoserine lactone (AHL) as signal molecules; b) peptide based signaling system
in Gram positive bacteria; and c) LuxS-encoded autoinducer-2 (AI-2), which is utilized by both Gram negative as well as Gram positive bacteria (Saxena et al. 2019;
Liu et al. 2018). The AHL signaling molecules are biosynthesized by LuxI protein
and are capable of diffusing across cell membrane. With an increase in cell density,
AHL are recognized by transcriptional regulator protein LuxR. This LuxR-AHL
complex triggers transcription of several genes and play an important role in biofilm
maturation. In P. aeruginosa, LasR-30C12-HSL complex differentially activates
several genes in concentration dependent manner. P. aeruginosa LasI mutants have
impaired 30C12-Homo Serien Lactone (HSL) synthesis and subsequently affected
biofilm maturation. Adding LasI generated 30C12-HSL quorum sensing signal
could restore the biofilm architecture (Parsek and Greenberg 2000). Unlike Gram
negative bacterial species, Gram positive species utilize peptides of varying length
(5 to 87 amino acids) as quorum sensing signal molecules. S. pneumoniae utilizes a
17-residue competence stimulating peptide (CSP) quorum sensing and S. mutans
uses 21 a/a CSP quorum sensing to induce genetic competence during promoted
biofilm growth (Okada et al. 2005). Bacillus subtilis and Staphylococcus aureus
have Ser/Thr kinases mediated regulation of biofilm growth. PrkC is a dimeric Ser/
Thr kinase like auto phosphorylating protein found in B. subtilis cell membrane that
also phosphorylates external myelin basic protein (MBP). S. aureus has Ser/Thr
kinase like Stk1 protein that phosphoryltes LuxS protein to eliminate production of
AI-2, thereby causing biofilm formation (Cluzel et al. 2010).
7.4 Biofilm Associated Multidrug Resistance
Numerous research studies have reported the high drug tolerance of bacteria in biofilms. Multi cellularity of biofilms confers protection to these cells. This tolerance
is due to the intrinsic genetic drift from the free floating lifestyle to surface adhered
forms (Romeo 2008; Sánchez et al. 2019). There are several hypothesis given to
explain the high recalcitrance in biofilm bacteria such as development of concentration gradient of substrates create localized microenvironments, effective management of stress response within biofilms in certain bacterial cells, slowed or blocked
penetration of antimicrobials in biofilms due to extracellular matrix, biofilms act as
a reservoir of persisters. In planktonic state, there is excess of nutrients that bacteria
can utilize but is unable to deplete substrates from the neighbouring cells due to not
enough metabolic activity (Donlan 2002). On other hand, coordinated and
B. P. Singh et al.