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6.3 Mechanism of Nanoparticle-Mediated Toxicity
to Control Antibiotic-Resistant Bacteria
The mechanism of nanoparticle-mediated control of antibiotic resistance in bacteria
is a relatively new area of research and various studies are being carried out to
understand bacterial response to nanoparticles. The various types of approaches
which are possibly responsible for nanoparticle-assisted damage to the bacterial
cells have been discussed in detail below.
(i) Effect on Bacterial Membrane
The bacterial membrane forms the first barrier to nanoparticles. Previously conducted studies have found that Gram-positive bacteria are more prone to damage by
nanoparticles as compared to Gram-negative ones. This difference is due to the cell
wall structure in both types of bacteria. The Gram-negative bacteria have an additional outer layer containing lipopolysaccharides which confers resistance to most
of the drugs and other hydrophobic compounds (Hajipour et al. 2012). Grampositive bacteria, on the other hand, possess a thick peptidoglycan-layered cell wall
(≈80 nm thick) with covalently attached teichoic acids. This protective layer is
comparatively less complex both physically and chemically as compared to the
Gram-negative bacteria where an outer membrane is present.
Various studies have shown the effects of different types of nanoparticles on the
membrane. For instance, Liu et al. (2009) found that zinc oxide nanoparticles caused
deformation of the membrane and led to the leakage of the intracellular components
of E. coli. In another study, the effect of titanium dioxide nanoparticles was studied
on E. coli membrane and a similar damaged membrane resulting in the leakage of
cellular components was observed. Based on these results, the possible mechanism
of nanoparticle-mediated membrane damage was elucidated by means of a fluorescent dye, 1-N-phenylnaphthylamine. The uptake of this dye was increased with an
increase in the concentrations of nanoparticle exposure indicating membrane rupture (Ranjan and Ramalingam 2016).
Since silver nanoparticles have been extensively used as antibacterial agents,
their mechanism of action has been proposed by recently conducted studies. These
nanoparticles dissolute in the presence of H 2 O 2 /O 2 which results in their easy uptake
by the cellular membrane under the influence of the proton motive force (AshaRani
et al. 2008; Choi and Hu 2008). It has also been studied that exposing the cells to
millimolar concentrations of silver nanoparticles leads to severe morphological
changes including shrinkage of cytoplasm and subsequent detachment of cell membrane leading to further degradation. This results in the leakage of intracellular
components. The above-described changes curb the growth of the bacteria. Studies
conducted in the recent past show the interaction of E. coli cells with silver nanoparticles. As revealed by transmission electron microscope images, the silver nanoparticles first adhere to the membrane and then penetrate within. Further, silver
nanoparticles with oxidized surfaces lead to the formation of large holes in the
membrane of E. coli and a substantial part of the cellular membrane seems to be lost
R. Sinha et al.
6.3 Mechanism of Nanoparticle-Mediated Toxicity
to Control Antibiotic-Resistant Bacteria
The mechanism of nanoparticle-mediated control of antibiotic resistance in bacteria
is a relatively new area of research and various studies are being carried out to
understand bacterial response to nanoparticles. The various types of approaches
which are possibly responsible for nanoparticle-assisted damage to the bacterial
cells have been discussed in detail below.
(i) Effect on Bacterial Membrane
The bacterial membrane forms the first barrier to nanoparticles. Previously conducted studies have found that Gram-positive bacteria are more prone to damage by
nanoparticles as compared to Gram-negative ones. This difference is due to the cell
wall structure in both types of bacteria. The Gram-negative bacteria have an additional outer layer containing lipopolysaccharides which confers resistance to most
of the drugs and other hydrophobic compounds (Hajipour et al. 2012). Grampositive bacteria, on the other hand, possess a thick peptidoglycan-layered cell wall
(≈80 nm thick) with covalently attached teichoic acids. This protective layer is
comparatively less complex both physically and chemically as compared to the
Gram-negative bacteria where an outer membrane is present.
Various studies have shown the effects of different types of nanoparticles on the
membrane. For instance, Liu et al. (2009) found that zinc oxide nanoparticles caused
deformation of the membrane and led to the leakage of the intracellular components
of E. coli. In another study, the effect of titanium dioxide nanoparticles was studied
on E. coli membrane and a similar damaged membrane resulting in the leakage of
cellular components was observed. Based on these results, the possible mechanism
of nanoparticle-mediated membrane damage was elucidated by means of a fluorescent dye, 1-N-phenylnaphthylamine. The uptake of this dye was increased with an
increase in the concentrations of nanoparticle exposure indicating membrane rupture (Ranjan and Ramalingam 2016).
Since silver nanoparticles have been extensively used as antibacterial agents,
their mechanism of action has been proposed by recently conducted studies. These
nanoparticles dissolute in the presence of H 2 O 2 /O 2 which results in their easy uptake
by the cellular membrane under the influence of the proton motive force (AshaRani
et al. 2008; Choi and Hu 2008). It has also been studied that exposing the cells to
millimolar concentrations of silver nanoparticles leads to severe morphological
changes including shrinkage of cytoplasm and subsequent detachment of cell membrane leading to further degradation. This results in the leakage of intracellular
components. The above-described changes curb the growth of the bacteria. Studies
conducted in the recent past show the interaction of E. coli cells with silver nanoparticles. As revealed by transmission electron microscope images, the silver nanoparticles first adhere to the membrane and then penetrate within. Further, silver
nanoparticles with oxidized surfaces lead to the formation of large holes in the
membrane of E. coli and a substantial part of the cellular membrane seems to be lost
R. Sinha et al.