This journal is © The Royal Society of Chemistry 2019 Metallomics, 2019, 11, 1265--1276 | 1265 Cite this: Metallomics, 2019, 11, 1265 Antibacterial mechanism of gold nanoparticles on Streptococcus pneumoniae† Edgar Augusto Ortiz-Benı ´ tez, a Norma Vela ´ zquez-Guadarrama, b Noe ´ Valentı ´ n Dura ´ n Figueroa, a He ´ ctor Quezada c and Jose ´ de Jesu ´ s Olivares-Trejo * d Streptococcus pneumoniae is a causal agent of otitis media, pneumonia, meningitis and severe cases of septicemia. This human pathogen infects elderly people and children with a high mortality rate of approximately one million deaths per year worldwide. Antibiotic-resistance of S. pneumoniae strains is an increasingly serious health problem; therefore, new therapies capable of combating pneumococcal infections are indispensable. The application of gold nanoparticles has emerged as an option in the control of bacterial infections; however, the mechanism responsible for bacterial cell lysis remains unclear. Specifically, it has been observed that gold nanoparticles are capable of crossing different structures of the S. pneumoniae cells, reaching the cytosol where inclusion bodies of gold nanoparticles are noticed. In this work, a novel process for the separation of such inclusion bodies that allowed the analysis of the biomolecules such as carbohydrates, lipids and proteins associated with the gold nanoparticles was developed. Then, it was possible to separate and identify proteins associated with the gold nanoparticles, which were suggested as possible candidates that facilitate the interaction and entry of gold nanoparticles into S. pneumoniae cells. Significance to metallomics Gold nanoparticles have antibacterial properties against Streptococcus pneumoniae; they lyse the bacterial cells after forming inclusion bodies of nanoparticles. The molecular mechanism is related to binding of carbohydrates, lipids and proteins. Introduction Streptococcus pneumoniae is a Gram-positive bacterium causal agent of many diseases such as otitis media, pneumonia, meningitis and septicemia. This bacterium has three structures that protect its integrity from the external environment. The most internal structure is the plasma membrane, which is composed by a phospholipid bilayer, 1 and contains glycerolipids with two chains of fatty acids. 2 The second structure that supports the S. pneumoniae cell is the wall, which is estimated to have a thickness of 20 to 80 nm and is composed of peptidoglycans (N-acetyl glucosamine and N-acetyl muramic acid) and lipotei- choic acid. 3,4 In the most external part, this pathogen has a capsule, which is composed of approximately six layers of polysaccharides. 5,6 There are antibacterials used to combat infections caused by S. pneumoniae such as penicillin, clindamycin, rifampicin, vancomycin and trimethoprim–sulfamethoxazole, 7,8 which affect those bacterial structures at different levels, for instance, the b-lactam antibiotics interfere with the assembly of pepti- doglycan, the main constituent of the bacterial cell wall. 9 The macrolides inhibit bacterial protein synthesis by binding to the large 50S ribosomal subunit and disrupting protein elongation because they dissociate the peptidyl-tRNA. 10 Although some antibiotics have shown great efficiency for a long time, their excessive use and incomplete treatment schemes have contrib- uted to the emergence of S. pneumoniae strains tolerant and resistant to antibiotics. The search for new alternatives that a Instituto Polite ´cnico Nacional, Unidad Profesional Interdisciplinaria de Biotecnologı ´a, Ciudad de Me ´xico, Mexico b Hospital Infantil de Me ´xico, Federico Gomez, Departamento de Infectologı ´a, Ciudad de Me ´xico, Mexico c Hospital Infantil de Me ´xico Federico Gomez, Laboratorio de Inmunologı ´a y Proteo´mica, Ciudad de Me ´xico, Mexico d Posgrado en Ciencias Geno´micas, Universidad Auto´noma de la Ciudad de Me ´xico, San Lorenzo 290, C.P. 03100, Ciudad de Me ´xico, Mexico. E-mail: olivarestrejo@yahoo.com; Tel: +52 5554886661, ext. 15309 † Electronic supplementary information (ESI) available. See DOI: 10.1039/ c9mt00084d Received 14th April 2019, Accepted 7th May 2019 DOI: 10.1039/c9mt00084d rsc.li/metallomics Metallomics PAPER Downloaded from https://academic.oup.com/metallomics/article/11/7/1265/5954231 by guest on 25 January 2023