posted on 2021-05-04, 23:43authored byYael N. Slavin, Kristina Ivanova, Javier Hoyo, Ilana Perelshtein, Gethin Owen, Anne Haegert, Yen-Yi Lin, Stephane LeBihan, Aharon Gedanken, Urs O. Häfeli, Tzanko Tzanov, Horacio Bach
The emergence of
bacteria resistant to antibiotics and the resulting
infections are increasingly becoming a public health issue. Multidrug-resistant
(MDR) bacteria are responsible for infections leading to increased
morbidity and mortality in hospitals, prolonged time of hospitalization,
and additional burden to financial costs. Therefore, there is an urgent
need for novel antibacterial agents that will both treat MDR infections
and outsmart the bacterial evolutionary mechanisms, preventing further
resistance development. In this study, a green synthesis employing
nontoxic lignin as both reducing and capping agents was adopted to
formulate stable and biocompatible silver–lignin nanoparticles
(NPs) exhibiting antibacterial activity. The resulting silver–lignin
NPs were approximately 20 nm in diameter and did not agglomerate after
one year of storage at 4 °C. They were able to inhibit the growth
of a panel of MDR clinical isolates, including Staphylococcus
aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter
baumannii, at concentrations that did not affect the
viability of a monocyte-derived THP-1 human cell line. Furthermore,
the exposure of silver–lignin NPs to the THP-1 cells led to
a significant increase in the secretion of the anti-inflammatory cytokine
IL-10, demonstrating the potential of these particles to act as an
antimicrobial and anti-inflammatory agent simultaneously. P. aeruginosa genes linked with efflux, heavy metal
resistance, capsular biosynthesis, and quorum sensing were investigated
for changes in gene expression upon sublethal exposure to the silver–lignin
NPs. Genes encoding for membrane proteins with an efflux function
were upregulated. However, all other genes were membrane proteins
that did not efflux metals and were downregulated.