title: Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin.
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.
authors.affiliation: Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University (KAU), Jeddah, 21589, Saudi Arabia.|Chemistry of Natural and Microbial Products Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Mervat Morsy Abbas Ahmed
authors.initials: MMAA
authors.lastname: El-Gendy
authors.affiliation: Medical Physiology Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Khaled G
authors.initials: KG
authors.lastname: Abdel-Wahhab
authors.affiliation: Medical Physiology Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Fathia A
authors.initials: FA
authors.lastname: Mannaa
authors.affiliation: Genetics and Cytology Department, National Research Centre, Dokki, Giza, Egypt.
authors.forename: Ayman A
authors.initials: AA
authors.lastname: Farghaly
authors.affiliation: Genetics and Cytology Department, National Research Centre, Dokki, Giza, Egypt. ahmed_bondkly@yahoo.com.
authors.forename: Ahmed M A
authors.initials: AMA
authors.lastname: El-Bondkly
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D063646:Carcinogenesis; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006460:Hemolysin Proteins / Q000096:biosynthesis; D006588:Hexanones / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D009578:Nitrobenzenes / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012449:Safety; D013094:Spermatozoa / Q000382:microbiology*; D013300:Streptokinase / Q000378:metabolism; D014774:Virulence / Q000187:drug effects
chemical_list: C561927:1,1-dichloro-4-ethyl-5-(4-nitrophenyl)hexan-2-one; D006460:Hemolysin Proteins; D006588:Hexanones; D009578:Nitrobenzenes; D013300:Streptokinase
keywords: Anti-virulent; Biofilm; Carcinogenic activity; Hemolysin; Sperm abnormality; Staphylococcus aureus (MRSA); Streptokinase