Reactive Oxygen Species (ROS)-Mediated Antibacterial Oxidative Therapies: Available Methods to Generate ROS and a Novel Option Proposal

Abstract

The increasing emergence of multidrug-resistant (MDR) pathogens causes difficult-to-treat infections with long-term hospitalizations and a high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treating MDR infections consists of inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS on mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks at 200-1000 °C in the limited presence of O₂. Recently, it has been demonstrated that BC's capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H₂O₂, or persulfate in the presence or absence of transition metals by electron transfer, thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC-containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

Keywords: advanced oxidation processes (AOPs); antimicrobial oxidative therapy; biochar (BC); biochar-derived permanent free radicals (PFRs); multidrug-resistant pathogens; reactive oxygen species (ROS).

Figure 1

Schematic pathways of reactive oxygen species (ROS) production and their main effects on biological systems. Nrf2 = erythroid nuclear transcription factor-2; NF-kB = transcription factor involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized low-density lipoproteins (LDL), etc. Reproduced from our article [11].

Figure 2

ROS induction by antibiotics as a secondary mechanism of their antibacterial effects.

Figure 3

Jablonski diagram showing the photochemical and photophysical mechanisms of antimicrobial photodynamic therapy (PDT). S₀: ground singlet state of the PS molecule; Sn: excited singlet state of the PS molecule; T₁: triplet excited state of the PS molecule; A: absorption of light; F: fluorescence emission; H: heat generation (internal conversion); ISC: inter-system crossing; P: phosphorescence emission; ³O₂: ground state oxygen; ¹O₂: singlet oxygen; O^2−•: superoxide anion; HO•: hydroxyl radical; H₂O₂: hydrogen peroxide. The image is an adaptation from an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/Licenses/by/4.0/ accessed on 22 May 2024), which permits unrestricted use, distribution, and reproduction in any medium [86].

Figure 4

Characteristics and criteria that a medical-grade honey (MGH) should fulfill, according to Hermann et al. [198].

Figure 5

HBOT enhances the immune system’s antimicrobial effects: Increased O₂ levels during HBOT have a variety of biological effects, including suppression of proinflammatory mediators, transitory reduction in the CD4:CD8 T cell ratio, and stimulation of lymphocyte and neutrophil death through caspase-3-, caspase-7-, and caspase-9-dependent mechanisms. In general, these effects can boost the antibacterial processes of the immune system and infection recovery. Abbreviations: ROS, reactive oxygen species; IL, interleukin; INF, interferon; TNF, tumor necrosis factor; CAS, caspase; NO, nitric oxide. Licensee: MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/ accessed on 22 May 2024) [240].

Figure 6

Events caused by hyperbaric oxygen therapy and the mechanisms by which its antibacterial effects derive.

Figure 7

Number of publications on BCs-derived PFRs from 2014 according to the Scopus dataset (reviews and chapters in books included). The survey used the following keywords: persistent AND free AND radicals AND biochar [24].

Scheme 1

Possible mechanisms leading to the formation of BC-bounded PFRs from lignin. The orange sphere represents biomass, while the black sphere represents BC, whose hypothetic structures depending on the pyrolysis condition have been shown at the bottom of the scheme [24].

Scheme 2

Possible mechanisms leading to the formation of BC-bounded graphitic PFRs from cellulose (left side) and emicellulose (right side). The orange sphere represents biomass, while the black sphere represents BC, whose hypothetic structures depending on the pyrolysis condition have been shown at the bottom of the scheme [24].