1887

Abstract

Gram-positive pathogens such as methicillin-resistant (MRSA) and vancomycin-resistant (VRE) have been frequently associated with bacterial resistance mechanisms. These mechanisms, in turn, restrict a range of therapeutic opportunities for the treatment of infections caused by these micro-organisms. Faced with this problem, the present study aims to isolate and characterize molecules with antimicrobial activity derived from the fungus isolated from Cerrado soil. Furthermore, we also tested possible antibacterial potential alone and in combination with commercial antimicrobial agents. In this context, citrinin was isolated and characterized by nuclear magnetic resonance and electrospray ionization. Functional analyses showed MIC of 128 µg ml against ATCC 25923, ATCC 29212 and a clinical isolate of vancomycin-resistant (VRE01). However, for a clinical strain of methicillin-resistant (MRSA01), the MIC was 256 µg ml. In order to avoid such high concentrations and reduce the collateral effects, additive effects were evidenced by combining citrinin with cefoxitin against MRSA01 (FIC index=0.5) and also citrinin with vancomycin toward VRE01 (FIC index=0.5). studies with BALB/c-tipe mice (MRSA assay) demonstrated a clinical ineffectiveness of cefoxitin associated with citrinin (9.8 mg kg of cefoxitin +0.2 mg kg of citrinin), with this combination being inefficient to increase animal survival. However, the combination used in the treatment of VRE (23.5 mg kg of citrinin +1.5 mg kg of vancomycin) sepsis model was extremely promising, leading to an animal survival rate of 80 percent. In summary, our data show, for the first time, the possible successful use of citrinin associated with vancomycin for pathogenic bacteria control.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000547
2017-11-01
2024-12-12
Loading full text...

Full text loading...

/deliver/fulltext/micro/163/11/1525.html?itemId=/content/journal/micro/10.1099/mic.0.000547&mimeType=html&fmt=ahah

References

  1. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D et al. Bad bugs, no drugs: no ESKAPE! an update from the infectious diseases society of America. Clin Infect Dis 2009; 48:1–12 [View Article][PubMed]
    [Google Scholar]
  2. Knoll BM, Hellmann M, Kotton CN. Vancomycin-resistant Enterococcus faecium meningitis in adults: case series and review of the literature. Scand J Infect Dis 2013; 45:131–139 [View Article][PubMed]
    [Google Scholar]
  3. Denkinger CM, Grant AD, Denkinger M, Gautam S, D'Agata EM. Increased multi-drug resistance among the elderly on admission to the hospital-a 12-year surveillance study. Arch Gerontol Geriatr 2013; 56:227–230 [View Article][PubMed]
    [Google Scholar]
  4. Climo MW, Yokoe DS, Warren DK, Perl TM, Bolon M et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med 2013; 368:533–542 [View Article][PubMed]
    [Google Scholar]
  5. Klein EY, Sun L, Smith DL, Laxminarayan R. The changing epidemiology of methicillin-resistant Staphylococcus aureus in the United States: a national observational study. Am J Epidemiol 2013; 177:666–674 [View Article][PubMed]
    [Google Scholar]
  6. Kang CI, Song JH. Antimicrobial resistance in Asia: current epidemiology and clinical implications. Infect Chemother 2013; 45:22–31 [View Article][PubMed]
    [Google Scholar]
  7. Raja NS, Karunakaran R, Ngeow YF, Awang R. Community-acquired vancomycin-resistant Enterococcus faecium: a case report from Malaysia. J Med Microbiol 2005; 54:901–903 [View Article][PubMed]
    [Google Scholar]
  8. Boyce JM. Environmental contamination makes an important contribution to hospital infection. J Hosp Infect 2007; 65:50–54 [View Article][PubMed]
    [Google Scholar]
  9. Barrett JF. MRSA: status and prospects for therapy? An evaluation of key papers on the topic of MRSA and antibiotic resistance. Expert Opin Ther Targets 2004; 8:515–519 [View Article][PubMed]
    [Google Scholar]
  10. Simor AE, Loeb M. CIDS/CAMM Guidelines Committee The management of infection and colonization due to methicillin-resistant Staphylococcus aureus: a CIDS/CAMM position paper. Can J Infect Dis 2004; 15:39–48 [View Article][PubMed]
    [Google Scholar]
  11. Arias CA, Contreras GA, Murray BE. Management of multidrug-resistant enterococcal infections. Clin Microbiol Infect 2010; 16:555–562 [View Article][PubMed]
    [Google Scholar]
  12. Sakoulas G, Bayer AS, Pogliano J, Tsuji BT, Yang SJ et al. Ampicillin enhances daptomycin- and cationic host defense peptide-mediated killing of ampicillin- and vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 2012; 56:838–844 [View Article][PubMed]
    [Google Scholar]
  13. Chen AY, Zervos MJ, Vazquez JA. Dalbavancin: a novel antimicrobial. Int J Clin Pract 2007; 61:853–863 [View Article][PubMed]
    [Google Scholar]
  14. Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother 2013; 57:3060–3066 [View Article][PubMed]
    [Google Scholar]
  15. Corey GR, Kabler H, Mehra P, Gupta S, Overcash JS et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med 2014; 370:2180–2190 [View Article][PubMed]
    [Google Scholar]
  16. Crotty MP, Krekel T, Burnham CA, Ritchie DJ. New Gram-positive agents: the next generation of oxazolidinones and lipoglycopeptides. J Clin Microbiol 2016; 54:2225–2232 [View Article][PubMed]
    [Google Scholar]
  17. Keller NP, Turner G, Bennett JW. Fungal secondary metabolism — from biochemistry to genomics. Nat Rev Microbiol 2005; 3:937–947 [View Article][PubMed]
    [Google Scholar]
  18. Wang X, Wang H, Liu T, Xin Z. A PKS I gene-based screening approach for the discovery of a new polyketide from Penicillium citrinum Salicorn 46. Appl Microbiol Biotechnol 2014; 98:4875–4885 [View Article][PubMed]
    [Google Scholar]
  19. Marinho AMR, Marinho PSB, Santos LS, Filho ER, Ferreira ICP. Active polyketides isolated from Penicillium herquei. An Acad Bras Cienc 2013; 85:909–912 [View Article][PubMed]
    [Google Scholar]
  20. Shen B. Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. Curr Opin Chem Biol 2003; 7:285–295 [View Article][PubMed]
    [Google Scholar]
  21. Subramani R, Kumar R, Prasad P, Aalbersberg W, Retheesh ST. Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp. Asian Pac J Trop Biomed 2013; 3:291–296 [View Article][PubMed]
    [Google Scholar]
  22. Razmavar S, Abdulla MA, Ismail SB, Hassandarvish P. Antibacterial activity of leaf extracts of Baeckea frutescens against methicillin-resistant Staphylococcus aureus. Biomed Res Int 2014; 2014:1–5 [View Article][PubMed]
    [Google Scholar]
  23. Reuk-ngam N, Chimnoi N, Khunnawutmanotham N, Techasakul S. Antimicrobial activity of coronarin D and its synergistic potential with antibiotics. Biomed Res Int 2014; 2014:1–8 [View Article][PubMed]
    [Google Scholar]
  24. Gonzalo X, Drobniewski F. Is there a place for β-lactams in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis? Synergy between meropenem and amoxicillin/clavulanate. J Antimicrob Chemother 2013; 68:366–369 [View Article][PubMed]
    [Google Scholar]
  25. Pena-Miller R, Laehnemann D, Jansen G, Fuentes-Hernandez A, Rosenstiel P et al. When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition. PLoS Biol 2013; 11:e1001540 [View Article][PubMed]
    [Google Scholar]
  26. Müller P, Alber DG, Turnbull L, Schlothauer RC, Carter DA et al. Synergism between medihoney and rifampicin against methicillin-resistant Staphylococcus aureus (MRSA). PLoS One 2013; 8:e57679 [View Article][PubMed]
    [Google Scholar]
  27. Clinical and Laboratory Standards Institute (CLSI) Performance Standards for Antimicrobial Disk Susceptibility Tests: Eleventh Edition Supplement M02-A11 Wayne, PA, USA: CLSI; 2012
    [Google Scholar]
  28. Orhan G, Bayram A, Zer Y, Balci I. Synergy tests by E test and checkerboard methods of antimicrobial combinations against Brucella melitensis. J Clin Microbiol 2005; 43:140–143 [View Article][PubMed]
    [Google Scholar]
  29. Divyashree BC, Vichwanatha T, Spoorthi NJ, Reena V, Aishwarya S et al. Evaluation of in vitro synergy between ampicillin and kanamycin against Staphylococcus aureus. J Clin Microbiol 2012; 2:144–146
    [Google Scholar]
  30. El-Desouky SK, Gamal-Eldeen AM. Cytotoxic and anti-inflammatory activities of some constituents from the floral buds of Syringa patula. Pharm Biol 2009; 47:872–877 [View Article]
    [Google Scholar]
  31. Lee SY, Kim HJ, Han JS. Anti-inflammatory effect of oyster shell extract in LPS-stimulated raw 264.7 cells. Prev Nutr Food Sci 2013; 18:23–29 [View Article][PubMed]
    [Google Scholar]
  32. King AM, Reid-Yu SA, Wang W, King DT, de Pascale G et al. Aspergillomarasmine a overcomes metallo-β-lactamase antibiotic resistance. Nature 2014; 510:503–506 [View Article][PubMed]
    [Google Scholar]
  33. Jang HC, Choi SM, Kim HK, Kim SE, Kang SJ et al. In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis. PLoS One 2014; 9:e101118 [View Article][PubMed]
    [Google Scholar]
  34. Arai M, Hibino T. Tumorigenicity of citrinin in male F344 rats. Cancer Lett 1983; 17:281–287 [View Article][PubMed]
    [Google Scholar]
  35. Chan WH, Shiao NH. Effect of citrinin on mouse embryonic development in vitro and in vivo. Reprod Toxicol 2007; 24:120–125 [View Article][PubMed]
    [Google Scholar]
  36. Bouslimi A, Ouannes Z, Golli EE, Bouaziz C, Hassen W et al. Cytotoxicity and oxidative damage in kidney cells exposed to the mycotoxins ochratoxin a and citrinin: individual and combined effects. Toxicol Mech Methods 2008; 18:341–349 [View Article][PubMed]
    [Google Scholar]
  37. Chagas GM, Campello AP, Klüppel ML. Mechanism of citrinin-induced dysfunction of mitochondria. I. Effects on respiration, enzyme activities and membrane potential of renal cortical mitochondria. J Appl Toxicol 1992; 12:123–129 [View Article][PubMed]
    [Google Scholar]
  38. Ribeiro SM, Campello AP, Chagas GM, Klüppel ML. Mechanism of citrinin-induced dysfunction of mitochondria. VI. Effect on iron-induced lipid peroxidation of rat liver mitochondria and microsomes. Cell Biochem Funct 1998; 16:15–20 [View Article][PubMed]
    [Google Scholar]
  39. Gomes NM, Bessa LJ, Buttachon S, Costa PM, Buaruang J et al. Antibacterial and antibiofilm activities of tryptoquivalines and meroditerpenes isolated from the marine-derived fungi Neosartorya paulistensis, N. laciniosa, N. tsunodae, and the soil fungi N. fischeri and N. siamensis. Mar Drugs 2014; 12:822–839 [View Article][PubMed]
    [Google Scholar]
  40. Arivudainambi US, Anand TD, Shanmugaiah V, Karunakaran C, Rajendran A. Novel bioactive metabolites producing endophytic fungus Colletotrichum gloeosporioides against multidrug-resistant Staphylococcus aureus. FEMS Immunol Med Microbiol 2011; 61:340–345 [View Article][PubMed]
    [Google Scholar]
  41. Deresinski S. Vancomycin in combination with other antibiotics for the treatment of serious methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2009; 49:1072–1079 [View Article][PubMed]
    [Google Scholar]
  42. Cottagnoud P, Cottagnoud M, Täuber MG. Vancomycin acts synergistically with gentamicin against penicillin-resistant pneumococci by increasing the intracellular penetration of gentamicin. Antimicrob Agents Chemother 2003; 47:144–147 [View Article][PubMed]
    [Google Scholar]
  43. Watanakunakorm C, Glotzbecker C. Enhancement of the effects of anti-staphylococcal antibiotics by aminoglycosides. Antimicrob Agents Chemother 1974; 6:802–806 [View Article][PubMed]
    [Google Scholar]
  44. Sande MA, Irvin RG. Penicillin-aminoglycoside synergy in experimental Streptococcus viridans endocarditis. J Infect Dis 1974; 129:572–576 [View Article][PubMed]
    [Google Scholar]
/content/journal/micro/10.1099/mic.0.000547
Loading
/content/journal/micro/10.1099/mic.0.000547
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error