Skip to main content

Advertisement

Log in

Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

This investigation aimed to study the in vivo harmful effects of the subcutaneous injection of different methicillin resistance Staphylococcus aureus extracts (MRSA2, MRSA4, MRSA10, MRSA69, MRSA70, MRSA76, and MRSA78). Such strains represented the highest minimum inhibition concentration toward methicillin with various multidrug-resistant patterns. The obtained results revealed that rats injected with the MRSA4 extract died immediately after the last dose indicating the high cytotoxicity of MRSA4 strain (100% mortality). While the mortalities in other groups injected by the other MRSA extracts ranged from 50 to 75%. In comparison with the normal animal group, all MRSA extracts induced a hepatotoxic effect which was indicated from the significant (p < 0.01) increases in the activities of the serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) enzymes. Moreover, alkaline phosphatase (ALP) combined with a partial nephrotoxicity that was monitored from the significant elevation of serum urea concentration. While serum creatinine levels did not affect. Similarly, a significant elevation was recorded in serum levels of tumor biomarkers (alpha fetoprotein; AFP, carcinoembryonic antigen; CEA, and lactate dehydrogenase; LDH) reflecting their carcinogenic potential. On the other hand, the percentage of micronuclei (MN) in polychromatic erythrocytes from bone marrow cells was statistically significant in all groups as compared to the control group. The percentage of sperm abnormalities was statistically significant compared to the control. Different types of head abnormalities and coiled tail were recorded. Consequently, the current study focused on fighting MRSA virulence factors by the new compound ayamycin, which proved to be potent anti-virulence factor against all MRSA strains under study by significant decreasing of their streptokinase activities, hemolysin synthesis, biofilm formation, and their cell surface hydrophobicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Velázquez, E., Peix, A., & Gómez-Alonso, A. (2011). Microorganisms and cancer: scientific evidence and new hypotheses. Cirugía Española, 89(3), 136–144. doi:10.1016/j.ciresp.2010.08.006.

    Article  Google Scholar 

  2. Kjellander, C., Björkholm, M., Källman, O., Giske, C. G., Weibull, C. E., Löve, T. J., Landgren, O., & Kristinsson, S. Y. (2016). Bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal single-center study. Annals of Hematology, 95(6), 871–879. doi:10.1007/s00277-016-2643-9.

    Article  Google Scholar 

  3. Fujiki, H., Nishitani, T. H. N., Suzuki, H. Y. K., Kurusu, M., & Suganuma, M. (2004). Carcinogenic potential of tobacco tar-resistant Staphylococcus aureus in buccal cavity. Journal of Cancer Research and Clinical Oncology, 130, 301–305.

    Article  CAS  Google Scholar 

  4. Wainwright, M. (2000). Highly pleomorphic Staphylococci as a cause of cancer. Medical Hypotheses, 54, 91–94.

    Article  CAS  Google Scholar 

  5. Edey, A. J., Bentley, P. G., Garrett, J. P., & Liebmann, R. D. (2005). Ductal breast carcinoma presenting with methicillin-resistant Staphylococcus aureus mastitis. The Breast Journal, 11, 491.

    Article  Google Scholar 

  6. Schneider, D., Liaw, L., Daniel, C., Athanasopoulos, A. N., Herrmann, M., & Preissner, K. T. (2007). Inhibition of breast cancer cell adhesion and bone metastasis by the extracellular adherence protein of Staphylococcus aureus. Biochemical and Biophysical Research Communications, 357, 282–288.

    Article  CAS  Google Scholar 

  7. Gupta, S., & Prabha, V. (2012). Human sperm interaction with Staphylococcus aureus: a molecular approach. Journal of Pathogens, 2012, 816536. doi:10.1155/2012/816536.

    Article  Google Scholar 

  8. Sanocka-Maciejewska, D., Ciupińska, M., & Kurpisz, M. (2005). Bacterial infection and semen quality. Journal of Reproductive Immunology, 67, 51–56.

    Article  CAS  Google Scholar 

  9. Salman, J. A. S., & Khudair, A. Y. (2015). Antibacterial and antibiofilm effect of biosurfactant produced from leuconostoc mesenteroides ssp. cremoris against bacteria from catheters. World J. Pharm. Res., 4(10), 320–333.

    CAS  Google Scholar 

  10. Ma, Y., Xu, Y., Yestrepsky, B. D., Sorenson, R. J., & Chen, M. (2012). Novel inhibitors of Staphylococcus aureus virulence gene expression and biofilm formation. PloS One, 7(10), e47255. doi:10.1371/journal.pone.0047255.

    Article  CAS  Google Scholar 

  11. Churkina, L., Vaneechoutte, M., Kiprianova, E., Perunova, N., Avdeeva, L., & Bukharin, O. (2015). Batumin—a selective inhibitor of Staphylococci-reduces biofilm formation in methicillin resistant Staphylococcus aureus. Open J. Med. Microbiol., 5, 193–201.

    Article  Google Scholar 

  12. El-Gendy, M. M. A., Hawas, U. W., & Jaspars, M. (2008). Novel bioactive metabolites from a marine derived bacterium Nocardia sp. ALAA 2000. The Journal of Antibiotics, 61(6), 379–386.

    Article  CAS  Google Scholar 

  13. Valette, H., Dolle, F., Bottlaender, M., Hinnen, F., & Marzin, D. (2002). Fluro-A-85380 demonstrated no mutagenic properties in vivo rat micronucleus and Ames tests. Nucl. Med. Boil., 9, 849–853.

    Article  Google Scholar 

  14. D’souza, U. J. A., Zain, A., & Raju, S. (2002). Genotoxic and cytotoxic effects bone marrow of rats exposed to low dose of paquat via the dermal route. Mutation Research, 581, 187–190.

    Article  Google Scholar 

  15. Wyrobek, A. J., & Bruce, W. R. (1978). The induction of sperm-shape abnormalities in mice and humans. In A. Hollaender & F. J. de Serres (Eds.), Principles and methods for their detection (Vol. 5, pp. 257–285). New York: Plenum Press.

    Google Scholar 

  16. Wyrobek, A. J., Gordon, L. A., Burkhart, J. G., Francis, M. W., Kapp, R. W., Letz, G., Malling, H. V., Tapham, J. C., & Whorton, M. D. (1983). An evaluation of the mouse sperm morphology test and other sperm tests in non-human mammals: a report of the gene. Mutation Research, 115, 1–72.

    Article  CAS  Google Scholar 

  17. Sun, H., Xu, Y., Sitkiewicz, I., Ma, Y., Wang, X., et al. (2012). Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice. Proceedings of the National Academy of Sciences of the United States of America, 109, 3469–3474.

    Article  CAS  Google Scholar 

  18. Courtney, H. S., Ofek, I., & Penfound, T. (2009). Relationship between expression of the family of M proteins and lipoteichoic acid to hydrophobicity and biofilm formation in Streptococcus pyogenes. PloS One, 4(1), e4166.

    Article  Google Scholar 

  19. Scheffer, J., Konig, W., Braun, V., & Goebel, W. (1988). Comparison of four hemolysin-producing organisms (Escherichia coli, Serratia marcescens, Aeromonas hydrophila, and Listeria monocytogenes) for release of inflammatory mediators from various cells. Journal of Clinical Microbiology, 26(3), 544–551.

    CAS  Google Scholar 

  20. Rubio, M., Palau, L., Vivas, J. R., delPotro, E., Diaz-Mediavilla, J., Alvarez, A., Martinez, R., & Picazo, J. J. (1994). Predominance of gram-positive microorganisms as a cause of septicemia in patients with hematological malignancies. Infection Control and Hospital Epidemiology, 15(2), 101–104.

    Article  CAS  Google Scholar 

  21. Gitlin, D., & Boseman, M. (1976). Fetus- specific serum proteins in several mammals and their relation to human α- fetoprotein. Com. Biochem. Physiol., 21, 327–336.

    Article  Google Scholar 

  22. Nakao, A., Tanigachi, K., Inoue, S., et al. (1996). Usefulness of simultaneous determination of alpha-fetoprotein and des-gamma carboxy prothrombin in hepatocellular carcinoma. Seminars in Surgical Oncology, 12(3), 160–163.

    Article  CAS  Google Scholar 

  23. El-Shobaky, A., Abbas, A., Raouf, R., Zakariab, M., & Ali El-Dein, B. (2015). Effect of pathogenic bacteria on reliability of CK-19, CK-20 and UPII as bladder cancer genetic markers: a molecular biology study. Egyptian j. Basic and Appl. Sci., 2, 176–182.

    Article  Google Scholar 

  24. Ohshima, H., Tatemichi, M., & Sawa, T. (2003). Chemical basis of inflammation-induced carcinogenesis. Archives of Biochemistry and Biophysics, 417(1), 3e11.

    Article  Google Scholar 

  25. Broussarda, G. W., Norrisb, M. B., Schwindtc, A. R., & Fournied, J. W. (2009). Chronic Mycobacterium marinum infection acts as a tumor promoter in Japanese Medaka. Biochem. Physiol. Toxicol. Pharmacol., 149(2), 152–160.

    Article  Google Scholar 

  26. Herrerea, L. A., Remirez, T., Rodriguez, U., Corona, T., Sotelo, J., & Lorenzo, M. (2000). Possible association between Taenia solium cysticercosis and cancer: increased frequency of DNA damage in peripheral lymphocytes from neurocysticercosis. Transactions of the Royal Society of Tropical Medicine and Hygiene, 94, 61–65.

    Article  Google Scholar 

  27. Campbell, E. S., Dickinson, C. J., Spater, J. D., Edward, C. W., & Sikora, K. (1984). Clinical physiology (5th ed.p. 446). London: Butter and Tanner Ltd..

    Google Scholar 

  28. Recknagel, R. O., Glendejr, E. A., & Briton, R. S. (1991). Free radical damage and lipid peroxidation. In R. G. Meeks (Ed.), Hepatotoxicology (pp. 401–436). Florida: CRC press.

    Google Scholar 

  29. Kaneko, J. J. (1989). Clinical biochemistry of domestic animals (4th ed.pp. 365–391). New York, London, Tokyo: Academic press, Inc..

    Google Scholar 

  30. Namin, B. M., Dallal, M. M. S., & Daryani, N. E. (2015). The effect of Campylobacter concisus on expression of IL-18, TNF-α and p53 in Barrett’s cell lines. Jundishapur J. Microbiol., 8(12), e26393. doi:10.5812/jjm.26393.

    Google Scholar 

  31. Wilson, J W. (2014). Bacterial Pathogens. In V. Stosor & T. R. Zembower (Eds.), Infectious complications in cancer patients. Cancer Treatment and Research (vol 161, p. 91–128, 1st ed.). Springer Science & Business Media.

  32. Brown, S. T., & Almenoff, P. L. (1992). Pulmonary mycobacterial infections associated with neoplasia. Seminars in Respiratory Infections, 7(2), 104–113.

    CAS  Google Scholar 

  33. Christen, S., Hagen, T. M., Shigenaga, M. K., & Ames, B. N. (1999). Chronic inflammation, mutation, and cancer. In J. Parsonet (Ed.), Microbes and malignancy: infection as a cause of human cancers (pp. 313–345). New York: Oxford Press.

    Google Scholar 

  34. Kumarasamy, V., Kuppusamy, U. R., Samudi, C., & Kumar, S. (2013). Blastocystis sp. subtype 3 triggers higher proliferation of human colorectal cancer cells, HCT116. Parasitology Research, 112(10), 3551–3555. doi:10.1007/s00436-013-3538-5.

    Article  Google Scholar 

  35. Antonelli, G. (2015). Why do infections cause cancer? Clinical Microbiology and Infection, 21(11), 967–968.

    Article  CAS  Google Scholar 

  36. Kaur, S., Prabha, V., & Sarwal, A. (2010). Receptor mediated agglutination of human spermatozoa by sperm agglutinating factor isolated from Staphylococcus aureus. J. Urology, 184(6), 2586–2590.

    Article  CAS  Google Scholar 

  37. Ji-Hong, L., Hao-Yong, L. I., Zheng-Guo, C. A. O., Yong-Fang, D., Yang, L. I., & Zhang-Qun, Y. E. (2002). Influence of several uropathogenic microorganisms on human sperm motility parameters in vitro. Asian J. Andrology, 4, 179–182.

    Google Scholar 

  38. Bakkiyaraj, D., & Pandian, S. K. (2010). In vitro and in vivo antibiofilm activity of a coral associated actinomycete against drug resistant Staphylococcus aureus biofilms. Biofouling, 26(6), 711–717.

    Article  CAS  Google Scholar 

  39. Gowrishankar, S., Mosioma, N. D., & Pandian, S. K. (2012). Coral-associated bacteria as a promising antibiofilm agent against methicillin-resistant and -susceptible Staphylococcus aureus biofilms. Evidence-Based Complementary and Alternative Medicine, 2012, 862374. doi:10.1155/2012/862374.

  40. Wu, S., Liu, G., Jin, W., Xiu, P., & Sun, C. (2016). Antibiofilm and anti-infection of a marine bacterial exopolysaccharide against Pseudomonas aeruginosa. Frontiers in Microbiology. doi:10.3389/fmicb.2016.00102.

    Google Scholar 

  41. Swiatlo, E., Champlin, F. R., Holman, S. C., Wilson, W. W., & Watt, J. M. (2002). Contribution of choline-binding proteins to cell surface properties of Streptococcus pneumoniae. Infection and Immunity, 70(1), 412–415.

    Article  CAS  Google Scholar 

  42. Caiazza, N. C., & Toole, G. A. O. (2003). Alpha-toxin is required for biofilm formation by Staphylococcus aureus. Journal of Bacteriology, 185(10), 3214–3217.

    Article  CAS  Google Scholar 

  43. Cheung, A. L., & Zhang, G. (2002). Global regulation of virulence determinants in Staphylococcus aureus by the SarA protein mily. Frontiers in Bioscience, 7, d1825–d1842.

    Article  CAS  Google Scholar 

  44. Trentin, D. S., Gorziza, D. F., Abraham, W. R., Antunes, A. L. S., Lerner, C., Mothes, B., Termignoni, C., & Macedo, A. J. (2011). Antibiofilm activity of Cobetia marina filtrates upon Staphylococcus epidermidis catheter-related isolates. Brazilian Journal of Microbiology, 42, 1329–1333.

    Article  CAS  Google Scholar 

  45. Sambanthamoorthy, K., Feng, X., Patel, R., Patel, S., & Paranavitana, C. (2014). Antimicrobial and antibiofilm potential of biosurfactants isolated from lactobacilli against multi-drug-resistant pathogens. BMC Microbiology, 14, 197.

    Article  Google Scholar 

Download references

Acknowledgments

Authors would like to thank the authorities of National Research Centre, Giza, Egypt, for providing the facilities and supporting by the fund (Project Code: 9100302) to carry out this work.

Contributors

El-Gendy MMAA, Abdel-Wahhab KG, Mannaa FA, Farghaly AA, and El-Bondkly AM designed the study, performed the experiments, managed literature searches, data analysis, and wrote the manuscript. All the authors read and approved the final manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ahmed M. A. El-Bondkly.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Gendy, M.M.A.A., Abdel-Wahhab, K.G., Mannaa, F.A. et al. Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin. Appl Biochem Biotechnol 183, 833–852 (2017). https://doi.org/10.1007/s12010-017-2467-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-017-2467-7

Keywords

Navigation