Functional Gold Nanoparticles as Potent Antimicrobial Agents against Multi-Drug-Resistant Bacteria

We present the use of functionalized gold nanoparticles (AuNPs) to combat multi-drug-resistant pathogenic bacteria. Tuning of the functional groups on the nanoparticle surface provided gold nanoparticles that were effective against both Gram-negative and Gram-positive uropathogens, including multi-drug-resistant pathogens. These AuNPs exhibited low toxicity to mammalian cells, and bacterial resistance was not observed after 20 generations. A strong structure–activity relationship was observed as a function of AuNP functionality, providing guidance to activity prediction and rational design of effective antimicrobial nanoparticles.

[1]  Vincent M. Rotello,et al.  Enzyme-amplified array sensing of proteins in solution and in biofluids. , 2010, Journal of the American Chemical Society.

[2]  M. SergioMella.  Trends in antimicrobial drug development: Implications for the future , 2005 .

[3]  David R. Spring,et al.  Combating Multidrug-Resistant Bacteria: Current Strategies for the Discovery of Novel Antibacterials , 2013 .

[4]  Xingyu Jiang,et al.  Multiple strategies to activate gold nanoparticles as antibiotics. , 2013, Nanoscale.

[5]  V. Rotello,et al.  Protein coronas suppress the hemolytic activity of hydrophilic and hydrophobic nanoparticles. , 2014, Materials horizons.

[6]  R. Murray,et al.  Dynamics of Place-Exchange Reactions on Monolayer-Protected Gold Cluster Molecules , 1999 .

[7]  M. Yin,et al.  Magnetic, electronic, and structural characterization of nonstoichiometric iron oxides at the nanoscale. , 2004, Journal of the American Chemical Society.

[8]  S. Levy,et al.  Molecular Mechanisms of Antibacterial Multidrug Resistance , 2007, Cell.

[9]  D. Astruc,et al.  Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. , 2004, Chemical reviews.

[10]  R. Murray,et al.  Monolayer-protected cluster molecules. , 2000, Accounts of chemical research.

[11]  S. Levy,et al.  Antibacterial resistance worldwide: causes, challenges and responses , 2004, Nature Medicine.

[12]  Sherine O. Obare,et al.  Nanoparticles Functionalized with Ampicillin Destroy Multiple-Antibiotic-Resistant Isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and Methicillin-Resistant Staphylococcus aureus , 2012, Applied and Environmental Microbiology.

[13]  R. Hancock,et al.  Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances , 2008, Nature Protocols.

[14]  E. Wang,et al.  Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle , 2013, Proceedings of the National Academy of Sciences.

[15]  J. Davies,et al.  Origins and Evolution of Antibiotic Resistance , 1996, Microbiology and Molecular Biology Reviews.

[16]  Keith E Maier,et al.  Growth inhibition of Staphylococcus aureus by mixed monolayer gold nanoparticles. , 2011, Small.

[17]  Roberta B Carey,et al.  Invasive methicillin-resistant Staphylococcus aureus infections in the United States. , 2007, JAMA.

[18]  N. Fujii,et al.  Molecular basis for membrane selectivity of an antimicrobial peptide, magainin 2. , 1995, Biochemistry.

[19]  G. Pugliese,et al.  Severe Streptococcus pyogenes Infections, United Kingdom, 2003–2004 , 2008, Emerging infectious diseases.

[20]  Katsumi Matsuzaki,et al.  Control of cell selectivity of antimicrobial peptides. , 2009, Biochimica et biophysica acta.

[21]  A. Kumar.  Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States , 2008 .

[22]  A. Safari,et al.  Development of gentamicin-gold nanospheres for antimicrobial drug delivery to Staphylococcal infected foci , 2013, Drug delivery.

[23]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[24]  V. Rotello,et al.  Aggregation and interaction of cationic nanoparticles on bacterial surfaces. , 2012, Journal of the American Chemical Society.

[25]  A. Grace,et al.  Antibacterial efficacy of aminoglycosidic antibiotics protected gold nanoparticles- : A brief study , 2007 .

[26]  Kieron M. G. O'Connell,et al.  Combating multidrug-resistant bacteria: current strategies for the discovery of novel antibacterials. , 2013, Angewandte Chemie.

[27]  M. B. Cardoso,et al.  Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with low cytotoxicity. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[28]  Ramasamy Venkatesan,et al.  Vancomycin bound biogenic gold nanoparticles: A different perspective for development of anti VRSA agents , 2011 .

[29]  J. Warmington,et al.  The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil) , 2000, Journal of applied microbiology.

[30]  Bing Xu,et al.  Presenting Vancomycin on Nanoparticles to Enhance Antimicrobial Activities , 2003 .

[31]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[32]  Xingyu Jiang,et al.  Small molecule-capped gold nanoparticles as potent antibacterial agents that target Gram-negative bacteria. , 2010, Journal of the American Chemical Society.

[33]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[34]  J. Powers,et al.  Trends in antimicrobial drug development: implications for the future. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[35]  Subinoy Rana,et al.  Sensing of proteins in human serum using conjugates of nanoparticles and green fluorescent protein. , 2009, Nature chemistry.

[36]  H. Nikaido.  Multidrug efflux pumps of gram-negative bacteria , 1996, Journal of bacteriology.

[37]  Mark A. Atwater,et al.  Extinction coefficient of gold nanoparticles with different sizes and different capping ligands. , 2007, Colloids and surfaces. B, Biointerfaces.

[38]  R. Desjardins,et al.  LIVE/DEAD BacLight : application of a new rapid staining method for direct enumeration of viable and total bacteria in drinking water. , 1999, Journal of microbiological methods.

[39]  H. Neu,et al.  The Crisis in Antibiotic Resistance , 1992, Science.

[40]  A. Alanis,et al.  Resistance to antibiotics: are we in the post-antibiotic era? , 2005, Archives of medical research.

[41]  M. Kuroda,et al.  The emergence and evolution of methicillin-resistant Staphylococcus aureus. , 2001, Trends in microbiology.

[42]  Mathias Brust,et al.  Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid-liquid system , 1994 .

[43]  Vincent M. Rotello,et al.  Applications of Nanoparticles in Biology , 2008 .

[44]  Keith E Maier,et al.  Identification of antibiotics using small molecule variable ligand display on gold nanoparticles. , 2010, Chemical communications.

[45]  Dan Peer,et al.  Nanoparticle hydrophobicity dictates immune response. , 2012, Journal of the American Chemical Society.

[46]  G. Tew,et al.  Antibacterial and Hemolytic Activities of Quaternary Pyridinium Functionalized Polynorbornenes , 2008 .

[47]  C. Perry,et al.  Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and their application in antimicrobial coatings , 2010 .