We studied the characteristics of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains that caused enteritis. In a previous report, we demonstrated that both phenotypic and genotypic changes were associated with MRSA enteritis; and we hypothesized that the accessory gene regulator (agr), which is a global regulator of staphylococcal virulence and upregulates several exoproteins, is the key factor associated with the development of MRSA enteritis. In this study, we examined 12 MRSA isolates associated with enteritis from stool samples and 17 MRSA isolates not associated with enteritis that had the following characteristics: the strains associated with enteritis had the same genotype (genotype A), as detected by pulsed-field gel electrophoresis, or the strains were isolated from stools. The differences between strains that caused enteritis and those that did not cause enteritis strains were examined by quantitative reverse transcription-PCR to assess RNAII, agrA, RNAIII, and tst expression and by sequencing of the agr locus. The levels of expression of agrA, RNAIII, and tst were higher by the MRSA isolates associated with enteritis than by the MRSA isolates not associated with enteritis, whether or not they were of the same genotype. The levels of expression of RNAII by almost all the clinical isolates were similar. Sequencing of the agr locus showed that all MRSA isolates that caused enteritis have agr mutations, whereas the MRSA isolates that did not cause enteritis, with three exceptions, did not. Many of the isolates associated with enteritis had the same mutation, especially at the C-terminal end of agrA. These results suggest a trend in which mutations in the agr locus modify the expression of agrA and RNAIII and the production of toxin, all of which may increase the virulence and influence the occurrence of MRSA enteritis.Severe postsurgical enteritis caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) (MRSA enteritis) was prevalent in Japan in the early 1990s. In the late 1990s, most patients with MRSA enteritis were successfully treated with vancomycin, and the number of cases with MRSA enteritis gradually decreased, but whenever it occurred, it was associated with a severe clinical course and, occasionally, death (12,28).Several studies have discussed the characteristics of isolates causing MRSA enteritis. Staphylococcal enterotoxin typing, coagulase typing, and toxic shock syndrome toxin 1 (TSST-1) titers are used as markers of MRSA enteritis (10, 30, 31). Many studies have described the phenotypes of isolates that cause enteritis, but there have been only a few reports on the genomic analysis of MRSA strains that cause enteritis (36). Our laboratory has studied the molecular epidemiology of MRSA enteritis strains by using pulsed-field gel electrophoresis (PFGE) and other methodologies for more than three decades. Our work has provided evidence that the disappearance of MRSA enteritis may have resulted from the decreased incidence of enteritis-causing clones (21)...