Journal Article

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

El-Gendy, Mervat Morsy Abbas Ahmed, Farghaly, Ayman A., Abdel-Wahhab, Khaled G., El-Bondkly, Ahmed M. A., Mannaa, Fathia A.

2017

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Abnormalities / Alanine / Alanine transaminase / Alkaline phosphatase / Animals / Antibiotic resistance / antigens / Aspartate aminotransferase / aspartate transaminase / Biochemistry / Biocompatibility / biofilm / Biofilms / Biofilms - drug effects / Biofilms - growth & development / Biomarkers / Biotechnology / blood serum / Bone marrow / bone marrow cells / Carcinoembryonic antigen / Carcinogenesis / Carcinogens / Cell surface / Chemistry / Chemistry and Materials Science / Coiling / Creatinine / Cytotoxicity / Dose-Response Relationship, Drug / Drug resistance / enzyme activity / Erythrocytes / HeLa Cells / Hemolysin Proteins - biosynthesis / hemolysins / hepatotoxicity / Hexanones - adverse effects / Hexanones - pharmacology / Humans / Hydrophobic and Hydrophilic Interactions / Hydrophobicity / In vivo methods and tests / Kidney - microbiology / L-Lactate dehydrogenase / Lactate dehydrogenase / Lactic acid / Liver - microbiology / Male / Methicillin / methicillin-resistant Staphylococcus aureus / Methicillin-Resistant Staphylococcus aureus - cytology / Methicillin-Resistant Staphylococcus aureus - drug effects / Methicillin-Resistant Staphylococcus aureus - metabolism / Methicillin-Resistant Staphylococcus aureus - physiology / Micronuclei / minimum inhibitory concentration / mortality / Multidrug resistance / multiple drug resistance / nephrotoxicity / Nitrobenzenes - adverse effects / Nitrobenzenes - pharmacology / Rats / Rats, Sprague-Dawley / Safety / Serum levels / Sperm / spermatozoa / Spermatozoa - microbiology / Staphylococcus aureus / Staphylococcus infections / Statistical analysis / Statistical significance / Streptokinase / Streptokinase - metabolism / subcutaneous injection / Toxicity / Urea / Virulence / Virulence - drug effects / Virulence factors / Viruses