Abstract:
Antibiotic resistance in infection-causing bacteria has been an increasing and persistent issue in healthcare facilities and communities. As a result, the development and production of new classes of antibiotics has been on the decline, rendering it necessary for research to find alternative ways to treat and reverse antibiotic resistance in infection-causing bacteria. The use of nanomolecular complexes as drug delivery systems in combination with existing biocides has shown promising results in addressing resistance in many pathogenic microorganisms. The lack of knowledge pertaining to the mechanism of action of certain drugs or biocides, including nanomolecular complexes, has, however, been a major limitation in the drug discovery process. Many of these drugs have been tested and proven to be effective however, the bioactivity of said drugs is often speculative or unclear. In this study, the transcriptional and metabolic pathway responses were evaluated to identify co-regulated genes and pathways that were affected in response to the exposure of three synthesized iodine-containing nanomolecular complex drugs denoted as KS25, KS33 and KS51 on model clinical isolates Escherichia coli ATCC BAA-196 (TEM-10) and Staphylococcus aureus ATCC BAA-39. Using DESeq2, with RNA sequence data from the two model microorganisms, a total of 444 and 539 differentially expressed genes (DEG) were identified in E. coli and S. aureus, respectively. Several major biological processes and pathways were observed in response to the three iodine-containing complexes, including the destruction of barriers, the induction of oxidative stress response genes, the activation and/or deactivation of several biosynthesis pathways such as a change in cellular respiration, amino acid, and nucleotide biosynthesis, mainly caused by halogen/iodine oxidation. The findings further indicated that the way in which the nanomolecular complexes exert their antibacterial effects is bacterial-growth-phase dependent i.e., the effects of the complexes slightly differ in each growth-phase, in which the model organisms were treated at. The complexes were additionally, found to be influenced by the materials used to synthesize them and by their environmental surroundings i.e., the presence of surrounding metal ions that could possibly bind to the nanomolecular complexes and further influencing their bioactivity. This study, therefore, aimed to evaluate the bioactivity of iodine entrapped in the three nanomolecular complexes. In analyzing the effects of these drug complexes on Gram-positive and Gram-negative model organisms, the mechanism of action, sensitivity, and factors influencing the bioactivity of iodine may have been determined, thus bettering the knowledge and the facilitation of the development of potential therapeutic antibacterial agents.
