  Citation: Mammari, N.; Lamouroux, E.; Boudier, A.; Duval, R.E. Current Knowledge on the Oxidative-Stress- Mediated Antimicrobial Properties of Metal-Based Nanoparticles. Microorganisms 2022, 10, 437. https://doi.org/10.3390/ microorganisms10020437 Academic Editor: Grzegorz Wegrzyn Received: 23 December 2021 Accepted: 9 February 2022 Published: 14 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. 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/). microorganisms Review Current Knowledge on the Oxidative-Stress-Mediated Antimicrobial Properties of Metal-Based Nanoparticles Nour Mammari 1 , Emmanuel Lamouroux 1 , Ariane Boudier 2 and Raphaël E. Duval 1,3, * 1 Université de Lorraine, CNRS, L2CM, F-54000 Nancy, France; nour.mammari@univ-lorraine.fr (N.M.); emmanuel.lamouroux@univ-lorraine.fr (E.L.) 2 Université de Lorraine, CITHEFOR, F-54000 Nancy, France; ariane.boudier@univ-lorraine.fr 3 ABC Platform®, F-54505 Vandœuvre-lès-Nancy, France * Correspondence: raphael.duval@univ-lorraine.fr; Tel.: +33-(0)372-747-218 Abstract: The emergence of multidrug-resistant (MDR) bacteria in recent years has been alarming and represents a major public health problem. The development of effective antimicrobial agents remains a key challenge. Nanotechnologies have provided opportunities for the use of nanomaterials as components in the development of antibacterial agents. Indeed, metal-based nanoparticles (NPs) show an effective role in targeting and killing bacteria via different mechanisms, such as attraction to the bacterial surface, destabilization of the bacterial cell wall and membrane, and the induction of a toxic mechanism mediated by a burst of oxidative stress (e.g., the production of reactive oxygen species (ROS)). Considering the lack of new antimicrobial drugs with novel mechanisms of action, the induction of oxidative stress represents a valuable and powerful antimicrobial strategy to fight MDR bacteria. Consequently, it is of particular interest to determine and precisely characterize whether NPs are able to induce oxidative stress in such bacteria. This highlights the particular interest that NPs represent for the development of future antibacterial drugs. Therefore, this review aims to provide an update on the latest advances in research focusing on the study and characterization of the induction of oxidative-stress-mediated antimicrobial mechanisms by metal-based NPs. Keywords: metal-based nanoparticles; oxidative stress; ROS; antibacterial activity; antibacterial mechanisms 1. Introduction The World Health Organization (WHO) states that the indiscriminate use of antibiotics has facilitated increasing bacterial resistance, and this has become a serious public health problem worldwide. Microbes, mainly bacteria, are now frequently resistant to several antibiotics; consequently, therapeutic options become more and more limited, and, con- comitantly, nosocomial infections more and more severe [1]. The situation is so critical that in 2017 WHO published a list of 12 resistant bacteria which represent a real threat to human health [1,2]. These bacteria are divided by WHO into three groups according to their emergency profile in relation to resistance to antibiotics. The first group is bacteria classified as a priority, also called “Critical Urgency” and includes: Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. They are Gram-negative bacteria, carbapenem- resistant, and third-generation-cephalosporin resistant. The second group is “High Urgency” and includes: vancomycin-resistant Enterococcus faecium, methicillin- and vancomycin- resistant Staphylococcus aureus, clarithromycin-resistant Helicobacter pylori, fluoroquinolone- resistant Campylobacter spp. and Salmonella spp., and third-generation-cephalosporin- and fluoroquinolone-resistant Neisseria gonorrhoeae. The third group is “Medium Urgency” and includes: penicillin-non-susceptible Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, and fluoroquinolone-resistant Shigella spp. [1,2]. Moreover, researchers have indicated that bacterial resistance to antibiotics due to genetic modification is correlated mainly with antibiotic consumption, and abundant antibiotic prescriptions are associated with the development of antibiotic resistance [3]. It is Microorganisms 2022, 10, 437. https://doi.org/10.3390/microorganisms10020437 https://www.mdpi.com/journal/microorganisms