153
(Ramalingam et al. 2016). Silver nanoparticles have also reportedly led to the formation of irregular-shaped pits in the outer membrane of E. coli, resulting in leakage of lipopolysaccharide molecules and proteins (Kaweeteerawat et al. 2017). The
detrimental effects of silver nanoparticles have also been reported for P. aeruginosa,
V. cholera, and S. typhus (Dos Santos et al. 2014; Franci et al. 2015). Not only silver
nanoparticles but also silver nanocomposites as well as silver nanoparticles modified with various surfactants interact with the bacterial membrane (Dallas et al. 2011).
(ii) Effect on Enzymes/Other Relevant Proteins
The interaction of nanoparticles on various proteins/enzymes is an important
area to understand the behavior of their action. It is documented that silver nanoparticles react with sulfur-containing proteins present on the cell surface (Rudramurthy
et al. 2016). Silver ions which are formed by the ionization of silver and its compounds have affinity for various proteins and amino acids. Similarly, gold nanoparticles also get attached with proteins as functional moieties (Baptista et al. 2008).
This helps in the increase in their antimicrobial efficacy.
Many drug-resistant bacteria remain functional in the presence of antibiotics due
to the presence of efflux pumps (Gupta et al. 2017). These efflux pumps are membrane transporter proteins and hence they help the bacteria to survive by extruding
the drug out of the cell. Nanoparticles have been possibly known to inhibit these
efflux pumps thereby inhibiting drug-resistant bacteria. A study was conducted to
investigate the bactericidal effect of zinc oxide nanoparticles on drug-resistant
S. aureus (Banoee et al. 2010). These nanoparticles were specifically targeted
against the NorA efflux pump of S. aureus. A considerable increase in the zone of
inhibition was observed for ciprofloxacin in the presence of zinc oxide nanoparticles indicating their ability to inhibit the efflux pump. Meanwhile, studies havealso
been conducted to coat or modify the surface of the nanoparticles to improve their
efficacy toward antibiotic-resistant bacteria. For example, polyacrylic acid-coated
FeO nanoparticles when administered along with rifampicin to Mycobacterium
smegmatis showed a four-fold increase in the growth inhibition as compared to the
antibiotic alone, suggesting the efflux inhibitory role of the modified nanoparticles
(Padwal et al. 2014). To further probe into the mechanism of nanoparticle-mediated
inhibition of efflux pumps, it was proposed that these probably bind to the active site
as competitive inhibitors of efflux pumps, thereby inactivating them, and hence their
ability to extrude the antibiotic out of the cell is impeded (Padwal et al. 2014).
Another mechanism which has been put forward is that these nanoparticles function
as efflux pump inhibitors by interfering with the efflux kinetics. Earlier studies also
proposed the disruption of the proton gradient by nanoparticles, which leads to the
disturbance of the proton motive force, thereby leading to a loss in the activity of
efflux pump (Choi et al. 2008; Dibrov et al. 2002).
Besides the antibacterial activity, nanoparticles are also being used for antiviral
activity as reported in studies (Huy et al. 2017; Lara et al. 2010a). For example,
silver nanoparticles in combination with the chitosan composites displayed antiviral
activity against H1N1 influenza virus (Mori et al. 2013). The study proposed that
one of the major factors responsible for the inhibitory activity of silver
6 Exploring Microbial Nanotoxicity Against Drug Resistance in Bacteria
(Ramalingam et al. 2016). Silver nanoparticles have also reportedly led to the formation of irregular-shaped pits in the outer membrane of E. coli, resulting in leakage of lipopolysaccharide molecules and proteins (Kaweeteerawat et al. 2017). The
detrimental effects of silver nanoparticles have also been reported for P. aeruginosa,
V. cholera, and S. typhus (Dos Santos et al. 2014; Franci et al. 2015). Not only silver
nanoparticles but also silver nanocomposites as well as silver nanoparticles modified with various surfactants interact with the bacterial membrane (Dallas et al. 2011).
(ii) Effect on Enzymes/Other Relevant Proteins
The interaction of nanoparticles on various proteins/enzymes is an important
area to understand the behavior of their action. It is documented that silver nanoparticles react with sulfur-containing proteins present on the cell surface (Rudramurthy
et al. 2016). Silver ions which are formed by the ionization of silver and its compounds have affinity for various proteins and amino acids. Similarly, gold nanoparticles also get attached with proteins as functional moieties (Baptista et al. 2008).
This helps in the increase in their antimicrobial efficacy.
Many drug-resistant bacteria remain functional in the presence of antibiotics due
to the presence of efflux pumps (Gupta et al. 2017). These efflux pumps are membrane transporter proteins and hence they help the bacteria to survive by extruding
the drug out of the cell. Nanoparticles have been possibly known to inhibit these
efflux pumps thereby inhibiting drug-resistant bacteria. A study was conducted to
investigate the bactericidal effect of zinc oxide nanoparticles on drug-resistant
S. aureus (Banoee et al. 2010). These nanoparticles were specifically targeted
against the NorA efflux pump of S. aureus. A considerable increase in the zone of
inhibition was observed for ciprofloxacin in the presence of zinc oxide nanoparticles indicating their ability to inhibit the efflux pump. Meanwhile, studies havealso
been conducted to coat or modify the surface of the nanoparticles to improve their
efficacy toward antibiotic-resistant bacteria. For example, polyacrylic acid-coated
FeO nanoparticles when administered along with rifampicin to Mycobacterium
smegmatis showed a four-fold increase in the growth inhibition as compared to the
antibiotic alone, suggesting the efflux inhibitory role of the modified nanoparticles
(Padwal et al. 2014). To further probe into the mechanism of nanoparticle-mediated
inhibition of efflux pumps, it was proposed that these probably bind to the active site
as competitive inhibitors of efflux pumps, thereby inactivating them, and hence their
ability to extrude the antibiotic out of the cell is impeded (Padwal et al. 2014).
Another mechanism which has been put forward is that these nanoparticles function
as efflux pump inhibitors by interfering with the efflux kinetics. Earlier studies also
proposed the disruption of the proton gradient by nanoparticles, which leads to the
disturbance of the proton motive force, thereby leading to a loss in the activity of
efflux pump (Choi et al. 2008; Dibrov et al. 2002).
Besides the antibacterial activity, nanoparticles are also being used for antiviral
activity as reported in studies (Huy et al. 2017; Lara et al. 2010a). For example,
silver nanoparticles in combination with the chitosan composites displayed antiviral
activity against H1N1 influenza virus (Mori et al. 2013). The study proposed that
one of the major factors responsible for the inhibitory activity of silver
6 Exploring Microbial Nanotoxicity Against Drug Resistance in Bacteria