There has been recent speculation that PVL in combination with the type IV SCCmec
element contributes to the spread of MRSA in the community, particularly in the context of SSTI (10
). The findings reported here are consistent with this idea. Over one-third of the hospital MRSA isolates and over two-thirds of the outpatient MRSA isolates were found to carry the lukS-PV-lukF-PV
gene complex; in contrast, less than 7% of the MSSA isolates were PVL+
. Most of the PVL+
isolates (96%) were MRSA, and all the PVL+
MRSA isolates carried the type IV SCCmec
element. The majority of the PVL+
MRSA strains were associated with SSTIs.
Two clonal groups, SF13:Z and SF16:S, dominated the survey, accounting for 49% of the isolates in the four MRSA collections and for 33% of all the isolates surveyed. That 91% of all the PVL+ MRSA isolates were SF13:Z or SF16:S is consistent with the idea that PVL (or some other shared factor) contributes to the success of these two clonal groups. Of additional note, the SF16:S clonal group, a group that is 100% PVL+ type IV SCCmec MRSA, has in the course of 2 years effectively supplanted the SF13:Z clonal group as the predominant strain among clinical samples from both inpatients and outpatients at SFGH.
The SF13:Z clonal group belongs to the ST30 clonal lineage. ST30 strains harboring the SCCmec
type IV element have been recovered in Sweden, Germany, Spain, Argentina, and Greece (8
). The SF13:Z clonal group is indistinguishable in sequence type, SCCmec
type, and PVL carriage from an outbreak PVL+
MRSA strain recovered from Polynesian patients seen at an Australian hospital in 1998 (26
). It is possible that the Oceania strain and the SF13:Z clonal group share a common origin.
The SF16:S and SF16:C clonal groups possess distinctive PFGE banding patterns (Fig. ) despite belonging to the same MLST clonal lineage, ST8. SF16:S and SF16:C appear to correspond to the USA300 and USA500 groups described recently by McDougal et al. (23
). ST8 is a well-established lineage with worldwide distribution that includes MSSA strains and MRSA strains carrying each of the four SCCmec
); ST8 MRSA strains carrying the SCCmec
type IV element have been recovered previously in both Europe and the United States. PVL genes were detected in both SF16:S and SF16:C lineages, although at different frequencies; relatively few SF16:C isolates were PVL+
, and these were split between MRSA and MSSA, whereas all the SF16:S were PVL+
MRSA. There is a recent report indicating PVL carriage by an ST8 strain (37
); from the data given, it is not possible to determine whether this corresponds to an SF16:C or SF16:S strain. However, given the recent appearance of the SF16:S clonal group in this area and its rapid increase in prevalence, we speculate that SF16:S is recently derived from an SF16:C-like ancestor that underwent substantial genomic reorganization and a significant gain in fitness. Wherever the origin of the SF16:S clonal group, it is evident that this PVL+
type IV SCCmec
MRSA has spread to multiple sites throughout the United States (23
), including the large MRSA outbreak in Los Angeles county in 2002 (4
; F. Perdreau-Remington, E. Pan, H. Carleton, B. Diep, S. Harvey, and G. Sensabaugh, Abstr. 43rd Intersci. Conf. Antimicrob. Chemother., p. 382, abstr. K-1393, 2003).
gene complex was detected in six clonal groups in addition to SF13:Z, SF16:C, and SF16:S. Two clonal groups, SF1:K and SF25:P, were found to carry PVL at intermediate frequency (Table ). SF1:K corresponds in sequence type to ST1, and the PVL+
strains found in this area are thus linked to the PVL+
ST1 strains responsible for CA-MRSA infections in the U.S. Midwest (14
), of which the fully sequenced MW2 strain is representative (3
ST1 strains have been recently reported in the Northeastern United States, and their detection here indicates that they have achieved nationwide distribution. SF25:P belongs to the ST59 clonal lineage and is ubiquitous in the San Francisco area (9
); it has been associated with both community- and hospital-acquired infections. The remaining four PVL+
isolates detected in this survey are singletons within their clonal groups; the presence of PVL in these clonal groups has not been reported previously.
The detection of PVL genes in nine different clonal groups raises the question of their origin. The lukS-PV-lukF-PV
gene complex is carried on a prophage integrated in the S. aureus
genome. Three PVL-bearing prophage sequences—
MW2—have been determined, and apart from the region carrying the PVL gene complex, each differs considerably in gene organization and sequence (3
). Narita et al. (25
) provide evidence of multiple additional PVL bearing prophages. It is thus likely that the PVL-bearing prophages in the clonal groups identified here have independent origins. The presence of high-prevalence PVL+
strains such as SF13:Z and SF16:S, however, raises the possibility that these strains can serve as reservoirs for the propagation of PVL to other clonal groups.
Finally, the emergence of PVL+
type IV SCCmec
MRSA strains in the community raises the concern that these strains will migrate into the hospital setting (27
), and indeed, this study provides evidence that this is already happening. Heretofore, CA-MRSA strains have been susceptible to antibiotics other than the β-lactams, allowing alternative treatment options (24
). However, in the hospital setting, it likely that multidrug-resistant strains will emerge, and the appearance of SF16:S isolates resistant to ciprofloxacin, erythromycin, and tetracycline may represent the first wave of multidrug-resistant CA-MRSA.