Received: 1 July, 2009. Accepted: 27 October, 2009. Invited Review Dynamic Biochemistry, Process Biotechnology and Molecular Biology ©2009 Global Science Books Antibacterial Mechanisms of Metallic Nanoparticles: A Review Rabeah Rawashdeh • Yousef Haik * Center for Research Excellence in Nanobiosciences, University of North Carolina at Greensboro, 321 McIver St., Greensboro, NC 27402, USA Corresponding author: * Y_haik@uncg.edu ABSTRACT Given the slow approval rate for new antibiotics and the inability of current antibiotics to fully control bacterial infection, it is obvious that there is a great demand for unconventional biocides. Metallic nanoparticles, another possible route for fighting bacteria, should be considered. Metallic bactericidals have been in use for several years as external sanitizers and disinfectants and have shown biocidal effectiveness against both Gram-positive and Gram-negative bacteria, as well as against fungi. The mechanism of interaction of these metallic biocides includes protein membrane damage, production of superoxide radicals, and ions release that interact with the cellular granules and form condensed molecules. This article presents a review of the metallic nanoparticles antimicrobial mode of interaction against bacteria. _____________________________________________________________________________________________________________ Keywords: antibacterial action, scanning electron microscope, silver ions, target site Abbreviations: CFU, colony-forming unit; LB medium, Luria-Bertani medium; MRSA, methicillin-resistant Staphylococcus aureus; NP, nanoparticle; SDS, sodium dodecyl sulfate; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; SEM, scanning electron microscope; TEM, transmission electron microscope CONTENTS INTRODUCTION........................................................................................................................................................................................ 12 MECHANISMS OF ANTIBACTERIAL SILVER AGENTS ...................................................................................................................... 12 Silver ion interaction with proteins.......................................................................................................................................................... 13 THE ANTIBACTERIAL SILVER NANOPARTICLES .............................................................................................................................. 14 The target sites of silver nanoparticles..................................................................................................................................................... 15 Detection of variations in the antibacterial activity of Ag NPs ................................................................................................................ 15 Enhancement of the ion release as one antibacterial mechanism of Ag NPs ........................................................................................... 17 OTHER ANTIBACTERIAL METALLIC NPs ............................................................................................................................................ 18 CAN BACTERIA DEVELOP RESISTANCE TO SILVER NANOPARTICLES? ...................................................................................... 19 CONCLUSIONS .......................................................................................................................................................................................... 19 REFERENCES............................................................................................................................................................................................. 19 _____________________________________________________________________________________________________________ INTRODUCTION The last few years have seen an enormous increase of a host of antibiotic-resistant bacteria. In 2002, the US Center for Disease Control and Prevention (CDC) estimated that at least 90,000 deaths a year in the US could be attributed to bacterial infection, more than half caused by bacteria resis- tant to at least one commonly used antibiotic. In October, 2008 the CDC reported that the number of serious methi- cillin-resistant Staphylococcus aureus (MRSA) infections was close to 100,000 a year with almost 19,000 related fata- lities (Taubes 2008). The inability of current antibiotics to fully control bacterial infection coupled with the slow ap- proval rate for new antibiotics necessitates the research for unconventional biocidals. The use of nanoparticles (NPs) as antibacterial agents have been the subject of many studies (Sondi and Salopek- Sondi 2004; Lok et al. 2006; Song et al. 2006; Jung et al. 2008) and since Ag possesses natural antibacterial proper- ties that are strengthened at the nanoscale, the most NPs produced are made from Ag or combination of Ag and other compounds (Furno et al. 2004; Sondi and Salopek- Sondi 2004; Morones et al. 2005; Lok et al. 2006; Song et al. 2006; Shrivastava et al. 2007; Fernández et al. 2008; Krutyakov et al. 2008; Raffi et al. 2008). Antibacterial NPs are being incorporated into different commercial products such as paints (Kumar et al. 2008), antibacterial medical devices (Furno et al. 2004), dental fil- lings (Beyth et al. 2006) and household items like refrigera- tors (SAMSUNG, SRS583HDP 585L pewter side by side refrigerator) (Bi et al. 2008). The incorporation of NPs into different consumer pro- ducts resulted mainly in health protection; however, the me- chanisms of the antibacterial NPs are not well understood and still an expanding field of research. Antibacterial action of NPs are studied by using different assays to detect the damage occur to bacterial cells. The antibacterial impact of NPs is induced commonly on two macromolecules, which are the genetic material DNA and the proteins found either throughout the cell membrane or inside the cells. MECHANISMS OF ANTIBACTERIAL SILVER AGENTS The most used antibacterial NPs are the Ag NPs which are produced extensively and used as antibacterial agents in various fields; to reduce infections in burn treatment (Klaus et al. 1999) and to eliminate microorganisms on textile fab- rics (Perelshtein et al. 2008a). Moreover, Ag NPs showed effective antiviral results against HIV infected cells (Elechi- ®