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耐甲氧西林金黄色葡萄球菌的致癌活性与精子异常以及阿亚霉素对其毒力潜能的抑制作用

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

作者信息

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

机构信息

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.

出版信息

Appl Biochem Biotechnol. 2017 Nov;183(3):833-852. doi: 10.1007/s12010-017-2467-7. Epub 2017 Apr 7.

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.

摘要

本研究旨在探讨皮下注射不同耐甲氧西林金黄色葡萄球菌提取物(MRSA2、MRSA4、MRSA10、MRSA69、MRSA70、MRSA76和MRSA78)的体内有害影响。这些菌株对甲氧西林表现出最高的最低抑菌浓度,并具有多种多重耐药模式。所得结果显示,注射MRSA4提取物的大鼠在最后一剂后立即死亡,表明MRSA4菌株具有高细胞毒性(100%死亡率)。而注射其他MRSA提取物的其他组死亡率在50%至75%之间。与正常动物组相比,所有MRSA提取物均诱导了肝毒性作用,这可从血清丙氨酸氨基转移酶(ALAT)和天冬氨酸氨基转移酶(ASAT)活性的显著(p < 0.01)升高看出。此外,碱性磷酸酶(ALP)升高并伴有部分肾毒性,这可从血清尿素浓度的显著升高监测到。而血清肌酐水平未受影响。同样,肿瘤生物标志物(甲胎蛋白;AFP、癌胚抗原;CEA和乳酸脱氢酶;LDH)的血清水平显著升高,反映了它们的致癌潜力。另一方面,与对照组相比,所有组骨髓细胞多色红细胞中的微核(MN)百分比具有统计学意义。与对照组相比,精子异常百分比具有统计学意义。记录到不同类型的头部异常和卷曲尾巴。因此,本研究聚焦于通过新化合物阿亚霉素对抗MRSA毒力因子,该化合物被证明是一种有效的抗毒力因子,可显著降低所研究的所有MRSA菌株的链激酶活性、溶血素合成、生物膜形成及其细胞表面疏水性。

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