The staphylococcal virulon is activated by the density-sensing agr system, which is autoinduced by a short peptide (autoinducing peptide [AIP]) processed from a propeptide encoded by agrD. A central segment of the agr locus, consisting of the C-terminal two-thirds of AgrB (the putative processing enzyme), AgrD, and the N-terminal half of AgrC (the receptor), shows striking interstrain variation. This finding has led to the division of Staphylococcus aureus isolates into three different agr specificity groups and to the division of non-aureus staphylococci into a number of others. The AIPs cross-inhibit the agr responses between groups. We have previously shown that most menstrual toxic shock strains belong to agr specificity group III but that no strong clinical identity has been associated with strains of the other two groups. In the present report, we demonstrate a fourth agr specificity group among S. aureus strains and show that most exfoliatin-producing strains belong to this group. A striking common feature of group IV strains is activation of the agr response early in exponential phase, at least 2 h earlier than in strains of the other groups. This finding raises the question of the biological significance of the agr autoinduction threshold.

IntroductionThe emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran.Materials and MethodsA total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing.ResultsThe MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 μg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%).ConclusionsThe circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.

The mec gene of a number of clinical methicillin-resistant Staphylococcus aureus isolates exhibiting a variety of heterogeneous expression modes was selectively inactivated by allelic replacement mutagenesis. While the resistance level of each of the transformants was reduced, the methicillin MIC for these transformants was well above the MIC for susceptible laboratory strains of S. aureus and was similar to the methicillin MIC for many contemporary clinical isolates which did not react with the mec-specific DNA probe but which showed a low or borderline level of resistance to methicillin. A number of those strains had no detectable I8-lactamase, and for about half of the isolates that did carry plasmid-borne j8-lactamase, elimination of the plasmid caused only partial reduction of the methicillin MIC or no reduction at all. The findings suggest that many contemporary strains of staphylococci harbor a combination of at least three distinct I8-lactam resistance mechanisms: (i) the mechanism related to the acquisition of the foreign mec gene and (ii) a ,B-lactamase-dependent and (iii) a I3-lactamase-independent mechanism, each one of which can provide a certain degree of resistance against penicillinase-resistant Il-lactam antibiotics.Methicillin-resistant clinical isolates of Staphylococcus aureus (MRSA) carry a complex, as yet only poorly understood resistance mechanism. All MRSA isolates examined so far have contained the mec gene, a 2,130-bp segment of foreign DNA coding for a low-affinity penicillin-binding protein (PBP 2A) (3,19,20). Despite the ubiquitous presence of this gene, MRSA isolates show tremendous variation in the MICs for the majority of the cells, and cultures of MRSA isolates are also heterogeneous: they contain a variable number of subpopulations for which the MICs range from very low to very high. Recently, it was shown that these complex modes of phenotypic expression are strain specific and appear to be under genetic control (37). In extreme cases, the methicillin MIC for the majority of bacteria (>99.99% of cells) may be as low as 3 p.g/ml (a MIC for susceptibility is 0.5 to 1.0 p.g/ml), despite the presence of the mec gene and its gene product (PBP 2A) in every cell. Similar, moderately increased MICs (4 to 8 p.g/ml) were also detected recently in some isolates which did not carry the mec gene, whether or not they produced f-lactamase (6, 36), the overproduction of which has been proposed as one mechanism that causes a moderate (borderline) elevation of the MIC of typically penicillinase-resistant antibiotics (6, 22, 23).One purpose of this study was to determine the relative contribution(s) of these mechanisms to the MIC for some selected MRSA isolates. Of particular interest was testing of the possibility that these distinct mechanisms may coexist in single isolates. An

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a therapeutic problem. In the present study, the molecular characterization by pulsed-field gel electrophoresis of MRSA isolates collected from a university hospital revealed that the predominant variant of the Brazilian epidemic clonal complex (BECC) was responsible for the increase in the incidence of MRSA strains, which reached 28% in 1998. It was verified that this predominant variant of the BECC displayed an enhanced ability to produce biofilm on inert polystyrene surfaces and to adhere to and invade epithelial airway cells. These results indicate that MRSA strains belonging to the BECC have evolved advantageous properties that might play a role in their predominance as international nosocomial pathogens.