Staphylococcus aureus isolates from hospital clinics induce ROS-mediated DNA damage, apoptosis and gene expression alterations in male mice

Abstract

Abstract Background One of the main pathogen that has been found widely spreading in the hospitals is Staphylococcus aureus. Moreover, developing antibiotic resistance to methicillin became an evidence of how low hygiene and unsanitary conditions can exist within hospitals. Such an environment can create a rich medium for the Methicillin-resistant Staphylococcus aureus (MRSA) bacteria to thrive and flourish. Since the spread of such bacteria and others like Klebsiella, Acinetobacter, and E. coli in hospitals is defined as a global crisis, stated by WHO, it was really crucial to conduct this study. Previous study was conducted in one of the governmental university hospitals due to the rapid spread of symptoms related to Staphylococcus which were reported from different patients and multiple specimens were collected. There was strong evidences of the cellular damage that caused by the infection with these isolates on the patients by the results received. Therefore, this study was conducted to study the effect of these isolates on ROS-mediated DNA adducts which usually associated with DNA damage followed signaling alteration of apoptotic related genes. Material and methods Clinical samples have been collected, DNA was extracted and PCR reaction was run on the samples to evaluate the presence of mecA gene to check for MRSA isolates. These isolates that have been selected to be ones used in the present study were injected as a suspension into male albino mice intraperitoneal. After 48\xa0h the mice were sacrificed and the whole liver was retrieved to assess apoptosis, determine Reactive Oxygen Species (ROS) formation and DNA adducts. Further studies have been made to analyze the expression of the apoptosis genes. Results The results found that mice exposed to MRSA positive control strain and MRSA isolates from wound, pus and ascitic fluid exhibited significantly the highest rates of ROS generation, OHdG/2-dG ratio and DNA damage in liver tissues of infected mice compared to the negative control group. Moreover, mice exposed to MRSA isolates (especially from wound, sputum, ascitic fluid, urine, blood and pus) exhibited significantly the highest rates of apoptosis and up-regulation of pro-apoptotic genes (caspase-3 and Bax) and down-regulation of anti-apoptotic gene (Bcl2) in their liver tissues compared to the negative control group. Conclusion These results suggested that the capability of genetically control of the mitochondrial pathway through gene expression manipulation could have therapeutic advantage in more fatal models of bacterial infection where increased apoptosis associated with mortality elevation.