title: Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.
abstract: Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis-BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis-GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus. Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections.
  
  
  BACKGROUND
  This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications.
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.
authors.forename: Rashmirekha
authors.initials: R
authors.lastname: Pati
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.
authors.forename: Ranjit Kumar
authors.initials: RK
authors.lastname: Mehta
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.
authors.forename: Soumitra
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Padhi
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.
authors.forename: Mitali
authors.initials: M
authors.lastname: Sengupta
authors.affiliation: Department of Animal Health and Management, Alagappa University, Karaikudi, Tamil Nadu, India.
authors.forename: Baskarlingam
authors.initials: B
authors.lastname: Vaseeharan
authors.affiliation: School of Biology, NISER, Bhubaneswar, Orissa, India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Goswami
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India. Electronic address: asonawane@kiitbiotech.ac.in.
authors.forename: Avinash
authors.initials: A
authors.lastname: Sonawane
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology; D009161:Mycobacterium / Q000187:drug effects* / Q000502:physiology; D009164:Mycobacterium Infections / Q000188:drug therapy; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D012867:Skin / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015034:Zinc Oxide
keywords: Antibacterial; Biofilm; Cytotoxicity; Inflammation; Mice; Pathogens; Skin infection; Zinc oxide nanoparticles