Biogenic Silver Nanoparticles as a Post-surgical Treatment for Corynebacterium pseudotuberculosis Infection in Small Ruminants

Caseous lymphadenitis (CL) is an infectious and zoonotic disease characterized by the development of granulomas in the lymph nodes and internal organs of small ruminants. The etiological agent of this disease is Corynebacterium pseudotuberculosis, a Gram-positive and facultative intracellular bacterium. The conventional treatment for CL consists of drainage and chemical cauterization of the lesions using a 10% iodine solution. However, this type of treatment is not effective, due to iodine’s cytotoxic profile and low antibacterial activity. Currently, silver nanoparticles (AgNPs) can be seen as an alternative treatment for CL due to their antimicrobial activity and wound healing effects. Therefore, the present study aimed to evaluate AgNPs as a post-surgical treatment for CL. Twenty-nine goats and sheep with clinical signs of CL were selected. Surgical intervention was performed to excise the caseous lesions. To treat the lesions, an ointment formulation based on AgNP mixed with natural waxes and oils was used in the experimental group, and the conventional treatment with 10% iodine was used in the control group. Bacteria were isolated from the excised caseous material. The animals were observed for 8 weeks after the surgical treatment, and blood samples were taken weekly. The surgical wounds of sheep treated with AgNP healed faster, and the surgical wound area was smaller during the observation period; the latter effect was also observed in goats. AgNP-treated animals also had less purulent discharge and less moisture in the surgical wounds. The AgNP-treated animals had lower leukocyte counts and lower titers of anti-C. pseudotuberculosis antibodies. There was no statistically significant difference between the groups with regard to the hemogram results. The results of the susceptibility testing of C. pseudotuberculosis strains (T1, 1002, FRC41, and VD57 strains) and clinical isolates to AgNPs showed growth inhibition, even at low concentrations. It can be concluded that post-surgical treatment of CL using the AgNP-based ointment may be a promising tool in the control of CL, through faster healing, decreased wound contamination, and no apparent toxic effects.

[1]  F. Paolicchi,et al.  Corynebacterium pseudotuberculosis , 2020, Definitions.

[2]  Caio H. N. Barros,et al.  NMR insights on nano silver post-surgical treatment of superficial caseous lymphadenitis in small ruminants , 2018, RSC advances.

[3]  Patrícia Yoshida Faccioli-Martins,et al.  Seroepidemiological characterization and risk factors associated with seroconversion to Corynebacterium pseudotuberculosis in goats from Northeastern Brazil , 2018, Tropical Animal Health and Production.

[4]  P. Aramwit,et al.  The downside of antimicrobial agents for wound healing , 2018, European Journal of Clinical Microbiology & Infectious Diseases.

[5]  M. Meylan,et al.  Clinical findings and diagnostic procedures in 270 small ruminants with obstructive urolithiasis , 2018, Journal of veterinary internal medicine.

[6]  B. Obradovic,et al.  Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments , 2018, Journal of biomaterials applications.

[7]  Marina Marinovich,et al.  In vitro assessment of silver nanoparticles immunotoxicity. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[8]  R. Salomoni,et al.  Antibacterial effect of silver nanoparticles in Pseudomonas aeruginosa , 2017, Nanotechnology, science and applications.

[9]  Ljubica Tasic,et al.  Antimicrobial textiles: Biogenic silver nanoparticles against Candida and Xanthomonas. , 2017, Materials science & engineering. C, Materials for biological applications.

[10]  V. N. Paunov,et al.  Colloid particle formulations for antimicrobial applications. , 2017, Advances in colloid and interface science.

[11]  Kangtaek Lee,et al.  5 nm Silver Nanoparticles Amplify Clinical Features of Atopic Dermatitis in Mice by Activating Mast Cells. , 2017, Small.

[12]  F. Sarrafzadeh-Rezaei,et al.  Effects of silver nanoparticles on Staphylococcus aureus contaminated open wounds healing in mice: An experimental study , 2017, Veterinary research forum : an international quarterly journal.

[13]  R. M. Nascimento,et al.  Humoral and cellular immune responses in mice against secreted and somatic antigens from a Corynebacterium pseudotuberculosis attenuated strain: Immune response against a C. pseudotuberculosis strain , 2016, BMC Veterinary Research.

[14]  A. Galandáková,et al.  Effects of silver nanoparticles on human dermal fibroblasts and epidermal keratinocytes , 2016, Human & experimental toxicology.

[15]  M. K. Swamy,et al.  Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes , 2016, Molecules.

[16]  S. H. Patil,et al.  Amelioration of excision wounds by topical application of green synthesized, formulated silver and gold nanoparticles in albino Wistar rats. , 2016, Materials science & engineering. C, Materials for biological applications.

[17]  D. Barh,et al.  Whole-genome optical mapping reveals a mis-assembly between two rRNA operons of Corynebacterium pseudotuberculosis strain 1002 , 2016, BMC Genomics.

[18]  D. Barh,et al.  The genome anatomy of Corynebacterium pseudotuberculosis VD57 a highly virulent strain causing Caseous lymphadenitis , 2016, Standards in Genomic Sciences.

[19]  A. El-Batal,et al.  Physiological Responses of Two Varieties of Common Bean (Phaseolus Vulgaris L.) to Foliar Application of Silver Nanoparticles , 2016 .

[20]  Rahisuddin,et al.  Biosynthesis of silver nanoparticles and its antibacterial and antifungal activities towards Gram-positive, Gram-negative bacterial strains and different species of Candida fungus , 2015, Bioprocess and Biosystems Engineering.

[21]  Stefania Galdiero,et al.  Silver Nanoparticles as Potential Antibacterial Agents , 2015, Molecules.

[22]  N. Cohen,et al.  In Vitro Susceptibility of Equine-Obtained Isolates of Corynebacterium pseudotuberculosis to Gallium Maltolate and 20 Other Antimicrobial Agents , 2014, Journal of Clinical Microbiology.

[23]  J. Bellare,et al.  Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics , 2013, International journal of nanomedicine.

[24]  V. Azevedo,et al.  Development of an indirect ELISA to detect Corynebacterium pseudotuberculosis specific antibodies in sheep employing T1 strain culture supernatant as antigen , 2013 .

[25]  S. Zinjarde,et al.  Psychrotrophic yeast Yarrowia lipolytica NCYC 789 mediates the synthesis of antimicrobial silver nanoparticles via cell-associated melanin , 2013, AMB Express.

[26]  S. Rossi,et al.  Wound dressings based on silver sulfadiazine solid lipid nanoparticles for tissue repairing. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[27]  G. Ertan,et al.  A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations. , 2012, International journal of nanomedicine.

[28]  Jiang-Jen Lin,et al.  Nanohybrids of Silver Particles Immobilized on Silicate Platelet for Infected Wound Healing , 2012, PloS one.

[29]  S. Spier,et al.  Survival of Corynebacterium pseudotuberculosis biovar equi in soil , 2012, Veterinary Record.

[30]  J. Cheon,et al.  Size dependent macrophage responses and toxicological effects of Ag nanoparticles. , 2011, Chemical communications.

[31]  V. Azevedo,et al.  High seroprevalence of caseous lymphadenitis in Brazilian goat herds revealed by Corynebacterium pseudotuberculosis secreted proteins-based ELISA. , 2010, Research in veterinary science.

[32]  L. Martínez-Martínez,et al.  Klebsiella pneumoniae AcrAB Efflux Pump Contributes to Antimicrobial Resistance and Virulence , 2009, Antimicrobial Agents and Chemotherapy.

[33]  R. Meyer,et al.  Evaluation of the humoral and cellular immune response to different antigens of Corynebacterium pseudotuberculosis in Canindé goats and their potential protection against caseous lymphadenitis. , 2008, Veterinary immunology and immunopathology.

[34]  Wei Huang,et al.  Facile preparation and characterization of highly antimicrobial colloid Ag or Au nanoparticles. , 2008, Journal of colloid and interface science.

[35]  M. Fontaine,et al.  Corynebacterium pseudotuberculosis and its role in ovine caseous lymphadenitis. , 2007, Journal of comparative pathology.

[36]  A. El-Darawany,et al.  Physiological traits as affected by heat stress in sheep—A review , 2007 .

[37]  Kwan Kim,et al.  A practical procedure for producing silver nanocoated fabric and its antibacterial evaluation for biomedical applications. , 2007, Chemical communications.

[38]  P. Berche,et al.  Corynebacterium pseudotuberculosis necrotizing lymphadenitis in a twelve-year-old patient. , 2006, The Pediatric infectious disease journal.

[39]  A. Miyoshi,et al.  Corynebacterium pseudotuberculosis: microbiology, biochemical properties, pathogenesis and molecular studies of virulence. , 2006, Veterinary research.

[40]  A. Iwasawa,et al.  [Cytotoxic effect and influence of povidone-iodine on wounds in guinea pig]. , 2003, Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases.

[41]  L. Williamson.  Caseous lymphadenitis in small ruminants. , 2001, The Veterinary clinics of North America. Food animal practice.

[42]  T. Shirahata,et al.  Role of Endogenous Tumor Necrosis Factor Alpha and Gamma Interferon in Resistance to Corynebacterium pseudotuberculosis Infection in Mice , 1998, Microbiology and immunology.

[43]  Nalin Rastogi,et al.  In Vitro Activities of Fourteen Antimicrobial Agents Against Drug Susceptible and Resistant Clinical Isolates of Mycobacterium tuberculosis and Comparative Intracellular Activities Against the Virulent H37Rv Strain in Human Macrophages , 1996, Current Microbiology.

[44]  M. Posada de la Paz,et al.  CLINICAL FINDINGS , 1978, WHO regional publications. European series.

[45]  A. B. Rodrigues,et al.  The use of nanoparticles in wound treatment: a systematic review. , 2018, Revista da Escola de Enfermagem da U S P.

[46]  Qiang Li,et al.  Bio fabrication of silver nanoparticles as an effective wound healing agent in the wound care after anorectal surgery. , 2018, Journal of photochemistry and photobiology. B, Biology.

[47]  M. S. Heydarnejad,et al.  Sliver nanoparticles accelerate skin wound healing in mice (Mus musculus) through suppression of innate immune system , 2014 .

[48]  Ana Milena,et al.  In vivo evaluation of antiseptics and disinfectants on control of Caseous Lymphadenitis: clinical, haematological, serological and microbiological monitoring Avaliação in vivo de antissépticos e desinfetantes no controle da Linfadenite Caseosa: acompanhamento clínico, hematológico, sorológico e micr , 2013 .

[49]  S. M. Estein,et al.  Desarrollo de una prueba de ELISA para detectar anticuerpos en carneros vacunados o infectados con Corynebacterium pseudotuberculosis , 2011 .

[50]  Andrew Burd,et al.  A comparative study of the cytotoxicity of silver‐based dressings in monolayer cell, tissue explant, and animal models , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.