3.11. Action of Metal NPs against bacteria
The external side of the cell wall of both Gram-positive and
Gram-negative bacteria bears negative charges due to the presence of
functional groups like carboxyl and phosphate and hydroxyl (Ashmore et
al., 2018). Gram-positive bacteria possess a thick peptidoglycan layer,
which resides in linear chains alternating residues of
N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) linked together
by a sequence of 3 to 5 amino acids that cross-link each other, giving
rise to a cohesive mesh. Additionally, negatively charged teichoic acids
(with high levels of phosphate groups) are spread from the cell wall to
the surface of most Gram-positive bacteria (Scheme S4.a) . In
contrast, Gram-negative bacteria display more complex structure with a
thinner layer of peptidoglycan and a phospholipid outer membrane with
partially phosphorylated lipopolysaccharides (LPS) that contribute to
raise the negative surface charge (Scheme S4.b) (Stensberg et
al., 2011).
Negatively charged bacterial cell walls interact with positively charged
particles such as metal cations via electrostatic interactions. Cations
may act through diverse pathways among which two seem to prevail in
aqueous media: (i) strong electrostatic interaction that
alter bacteria membrane equilibrium, and (ii ) Lewis
acid-base interaction with water molecules that generates Bronsted
acidity (Mn+ + xH2O =
[M(H2O)(x-1)OH](n-1)++ H+) that may alter bacteria membrane. The metal ions
are then free to interact with cellular structures (e.g.,proteins, membranes, DNA), disrupting cell functions (Ashmore et al.,
2018). In contrast, MNPs are supposed to interact via strong LAB
interaction with atoms bearing available electron pairs (O, S, and N)
that act as Lewis base. Such interactions are assumed to affect the
normal cell exchange through bacteria membrane. Other mechanisms such
MNP diffusion inside the cell and disrupt biological processes
(Stensberg et al., 2011). Inside the cell, both metal cation and
nanoparticles can generate reactive oxygen species (ROS) like hydrogen
peroxide (H2O2, superoxide anion
(· O2 −), and hydroxyl radical•OH (Gordon et al., 2010; Yun’an Qing et al., 2018).
These species are assumed to bind to phosphate groups inhibiting protein
phosphorylation frequently involved in enzymatic activation. This is
expected to inhibit bacterial growth and cell cycle through the
dephosphorylation of some important proteins for enzymatic activities
(Dakal, Kumar, Majumdar, & Yadav, 2016). Given that metals bind to
biomolecules through non-specific interactions, MNPs generally exhibit a
wide variety of processes against bacteria (Scheme S4.c) (Yuan,
Ding, Yang, & Xu, 2018).
Once inside the cell, both AgNPs and Ag+ ions interact
with diverse species resulting in cell dysfunction. Reportedly, AgNPs
can act through four main mechanism pathways: (i)
attraction on bacterial surface; (ii) destabilization of
the bacterial cell wall and increase in membrane permeability even for
larger AgNPs (Losasso et al., 2014); (iii) genesis of
ROS and free radicals that induce toxicity and oxidative stress;
(iv ) modification of signal transduction pathways (Dakal
et al., 2016). AgNP adsorption on the bacterial surface can be followed
by diffusion of smaller particle inside the cell and retention of larger
ones on the external side of the bacteria membrane. In spite of their
antibacterial activity (Ávalos, Haza, Mateo, & Morales, 2013), AgNPs
were found to be less performant that cations (El Badawy et al., 2011).
The latter are much more attracted by the negative charges of bacterial
walls (Slavin, Asnis, Häfeli, & Bach, 2017). However, AgNPs may also
act through partial dissolution into Ag+ cations, as
reported by many works. The Ag+ cations act
differently by binding to the cell membrane inducing changes in the
membrane potential and proton leakage (Losasso et al., 2014).
Reportedly, Ag+ cation may intercalate DNA segments
generating complexes with nucleotides and disrupting H-bonds between
base pairs (Yun’an Qing et al., 2018). Similar observations were made
for CuNPs where a Cu2+ release was found to be the
main contribution to the high antibacterial activity (Chatterjee,
Chakraborty, & Basu, 2014; Sistemática, Gabriela, Daniela, & Helia,
2016). As for silver, CuNP action may also involve diverse mechanisms,
the most reported by the literature being: (i ) CuNP
concentration and dissolution in the bacterial membrane inducing
potential and permeability changes, with unavoidable leak in
lipopolysaccharides, membrane proteins, intracellular biomolecules and
protons (Amro et al., 2000; Azam, Ahmed, Oves, Khan, & Memic, 2012).
(ii) production of ROS, MNPs oxidation and dissolution
into Cu2+ cation, with other detrimental oxidative
processes (Fenton, Harber-Weiss) processes (Applerot et al., 2012; Fang,
Lyon, Wiesner, Dong, & Alvarez, 2007); (iii)
Accumulation of Cu2+ cation with decay in
intracellular ATP production and disruption of DNA replication (Kim et
al., 2007; Sondi & Salopek-Sondi, 2004). These pathways should confer
higher activity to CuNPs against both bacteria compared with AgNPs
(Chudobová & Kizek, 2015).