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Fish represent a worldwide significant source of animal protein. In order to investigate the prevalence of MRSA in catfish as well as the inhibitory effect of Sidr honey on virulence genes of MRSA, fish were collected from Bahr Elbaker canal at Sharkia Governorate, Egypt. Swab samples were collected under complete aseptic conditions from internal organs (pancreas, liver, kidney and intestine), gills and skin then subjected to bacteriological examination. A total of 70 S. aureus strains were isolated from catfish, out of them 15 (21.42%) strains were identified as MRSA as a first record in Egypt. PCR was used for detection of meca, coa and spa genes in the isolated MRSA strains before and after the exposure to sidr honey. Before exposure to sider honey, all the selected MRSA strains showed positive results for meca, coa and spa genes with specific amplicon size of 310 bp, 430 bp and 226 bp, respectively. After exposure to sidr honey, MRSA strains showed inhibition of coa and spa genes, but has no effect on meca gene. In addition, scanning electron microscopy was used for detection of the morphological characters of MRSA strains before and after treatment with sidr honey. After exposure of MRSA strains to 30% (w/v) Sidr honey for 48 hours, cells surfaces were observable irregular with the appearance of cell debris. In conclusion, MRSA strains could be isolated from fresh water catfish in Egypt which may be attributed to the contamination of water and fish food. Sider honey showed a significant inhibitory effect on the growth of isolated MRSA strains. Moreover, it could inhibit spa and coa genes. SEM is a valuable tool revealing the abnormal morphological changes that take place in MRSA strains after exposure to Sidr honey. [ABSTRACT FROM AUTHOR]