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Dual Modality FeS Nanoparticles with Reactive Oxygen Species-Induced and Photothermal Toxicity toward Pathogenic Bacteria.

ABSTRACT: Bacterial infections pose a major threat to human health, primarily because of the evolution of mutated strains that are resistant to antibiotic treatment. As a viable alternative, several nanoparticles have emerged as attractive antibacterial agents. Herein, we report the development of iron sulfide (FeS) nanoparticles that show dual-modality therapy: namely reactive oxygen species (ROS)-induced toxicity and red-laser induced photothermal therapy. The aqueous synthesized nanoparticles have been characterized based on their size, shape, crystallinity, and magnetic and optical properties. These nanoparticles showed sustained release of Fe2+ ions in an aqueous dispersion. They also have a high absorption cross-section in the visible and near infra-red regions and could be excited by a continuous wave diode laser of wavelength 635 nm leading to significant hyperthermia. Nanoparticle treatment, followed by light irradiation, led to significant cell death in two ghastly pathogenic bacterial strains. Stepwise enhancement of intrabacterial ROS levels, as a result of nanoparticle treatment followed by light activation, has been identified as the primary antibacterial mechanism.

SUBMITTER: Agnihotri S

PROVIDER: S-EPMC6964285 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Dual Modality FeS Nanoparticles with Reactive Oxygen Species-Induced and Photothermal Toxicity toward Pathogenic Bacteria.

Agnihotri Shrish S Mohan Tarun T Jha Diksha D Gautam Hemant Kumar HK Roy Indrajit I

ACS omega 20200103 1

Bacterial infections pose a major threat to human health, primarily because of the evolution of mutated strains that are resistant to antibiotic treatment. As a viable alternative, several nanoparticles have emerged as attractive antibacterial agents. Herein, we report the development of iron sulfide (FeS) nanoparticles that show dual-modality therapy: namely reactive oxygen species (ROS)-induced toxicity and red-laser induced photothermal therapy. The aqueous synthesized nanoparticles have been ...[more]

PMID: 31956807

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Project description:Korormicin is an antibiotic produced by some pseudoalteromonads which selectively kills Gram-negative bacteria that express the Na+-pumping NADH:quinone oxidoreductase (Na+-NQR.) We show that although korormicin is an inhibitor of Na+-NQR, the antibiotic action is not a direct result of inhibiting enzyme activity. Instead, perturbation of electron transfer inside the enzyme promotes a reaction between O2 and one or more redox cofactors in the enzyme (likely the flavin adenine dinucleotide [FAD] and 2Fe-2S center), leading to the production of reactive oxygen species (ROS). All Pseudoalteromonas contain the nqr operon in their genomes, including Pseudoalteromonas strain J010, which produces korormicin. We present activity data indicating that this strain expresses an active Na+-NQR and that this enzyme is not susceptible to korormicin inhibition. On the basis of our DNA sequence data, we show that the Na+-NQR of Pseudoalteromonas J010 carries an amino acid substitution (NqrB-G141A; Vibrio cholerae numbering) that in other Na+-NQRs confers resistance against korormicin. This is likely the reason that a functional Na+-NQR is able to exist in a bacterium that produces a compound that typically inhibits this enzyme and causes cell death. Korormicin is an effective antibiotic against such pathogens as Vibrio cholerae, Aliivibrio fischeri, and Pseudomonas aeruginosa but has no effect on Bacteroides fragilis and Bacteroides thetaiotaomicron, microorganisms that are important members of the human intestinal microflora.IMPORTANCE As multidrug antibiotic resistance in pathogenic bacteria continues to rise, there is a critical need for novel antimicrobial agents. An essential requirement for a useful antibiotic is that it selectively targets bacteria without significant effects on the eukaryotic hosts. Korormicin is an excellent candidate in this respect because it targets a unique respiratory enzyme found only in prokaryotes, the Na+-pumping NADH:quinone oxidoreductase (Na+-NQR). Korormicin is synthesized by some species of the marine bacterium Pseudoalteromonas and is a potent and specific inhibitor of Na+-NQR, an enzyme that is essential for the survival and proliferation of many Gram-negative human pathogens, including Vibrio cholerae and Pseudomonas aeruginosa, among others. Here, we identified how korormicin selectively kills these bacteria. The binding of korormicin to Na+-NQR promotes the formation of reactive oxygen species generated by the reaction of the FAD and the 2Fe-2S center cofactors with O2.

Dataset Information

Dual Modality FeS Nanoparticles with Reactive Oxygen Species-Induced and Photothermal Toxicity toward Pathogenic Bacteria.

Publications

Dual Modality FeS Nanoparticles with Reactive Oxygen Species-Induced and Photothermal Toxicity toward Pathogenic Bacteria.

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