Abstract:
Iodine is one of the oldest antimicrobial agents. Until now, there have
been no reports on acquiring resistance to iodine. Recent studies showed promising
results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of the
action, however, remain unclear. The aim of this study was to perform a holistic
analysis and comparison of gene regulation in three phylogenetically distant multidrug-resistant reference strains representing pathogens associated with nosocomial
infections from the ATCC culture collection: Escherichia coli BAA-196, Staphylococcus
aureus BAA-39, and Acinetobacter baumannii BAA-1790. These cultures were treated
by a 5-min exposure to sublethal concentrations of the iodine-containing drug FS-1
applied in the late lagging phase and the middle of the logarithmic growth phase.
Complete genome sequences of these strains were obtained in the previous studies.
Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the
treatment of bacteria with FS-1 profoundly affected the expression of many genes
involved in the central metabolic pathways; however, alterations of the gene expression profiles were species specific and depended on the growth phase. Disruption of
respiratory electron transfer membrane complexes, increased penetrability of bacterial cell walls, and osmotic and oxidative stresses leading to DNA damage were the
major factors influencing the treated bacteria.
IMPORTANCE: Infections caused by antibiotic-resistant bacteria threaten public health
worldwide. Combinatorial therapy in which antibiotics are administered together
with supplementary drugs improving susceptibility of pathogens to the regular antibiotics is considered a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 has
been reported recently. This drug is currently under clinical trials in Kazakhstan
against multidrug-resistant tuberculosis. The effects of released iodine on metabolic
and regulatory processes in bacterial cells remain unexplored. The current work provides an insight into gene regulation in the antibiotic-resistant nosocomial reference
strains treated with iodine-containing nanoparticles. This study sheds light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when
applied in sublethal concentrations. This knowledge will aid in the future design of
new drugs against antibiotic-resistant infections.
