1. What is a SCCmec element?
The staphylococcal cassette chromosome mec (SCCmec) elements are one of SCCs, which are widely disseminated in staphylococci. SCCmec is specified from other SCCs by the carriage of methicillin resistant-determinant. MSSA changes to MRSA upon the acquisition of SCCmec. When the SCCmec excises from the MRSA chromosome, MRSA changes to MSSA.
Structural comparison of SCCmec elements.
2. Common characteristics of SCCmec elements
SCCmec elements identified to date commonly share the following characteristics.
(1) They carry a mec gene complex (mec).
(2) They carry a ccr gene complex (ccr).
(3) They have characteristic directly-repeated nucleotide sequences (DRs) and inverted-complementary sequences (IRs) at both ends.
(4) They integrate into ISS (integration site sequence for SCCmec), which is located at 3’ end of orfX.
In the structure of SCCmec elements, the regions other than ccr gene complex (ccr) and mec gene complex (mec) are designated junkyard (J) regions. The junkyard regions comprise three parts: J1 (the region between ccr and the chromosomal region flanking SCCmec), J2 (the region between mec and ccr), and J3 (the region between orfX and mec).
Diversities in the structure of SCCmec elements.
Despite the similarities described above, the structure of SCCmec elements are rather divergent. Allotypic differences have been identified in both ccr and mec. Four classes of mec and five types of ccr have been reported. Furthermore, the numerous differences in J regions have been identified. The SCCmec elements have been classified based on the differences in mec, ccr, and for subtyping, also the J regions.
(1) SCCmec type: defined by the combination of mec and ccr.
|SCCmec type||combination of ccr and mec|
|Type I||type-1 ccr carrying ccrA1 and B1 and class B mec (1B)|
|Type II||type-2 ccr carrying ccrA2 and B2 and class A mec (2A)|
|Type III||type-3 ccr carrying ccrA3 and B3 and class A mec (3A)|
|Type IV||type-2 ccr carrying ccrA2 and B2 and class B mec (2B)|
|Type V||type-5 ccr carrying ccrC and class C mec (5C)|
|Type VI||type-4 ccr carrying ccrA4 and B4 and class B mec (4B)|
|Type VII||type-5 (C1) ccr and class C1 mec(5C1)|
|Type VIII||type-4 (A4B4) ccr and class A mec(4A)|
|Type IX||type-1(A1B1) ccr and class C2 mec(1C2)|
|TypeX||type-7(A1B6) ccr and class C1 mec(7C1)|
|Type XI||type-8(A1B3) ccr and class E mec(8E)|
(2) Subtypes : defined by the structural differences in J1, -2 and -3 regions
The J regions are not always specific to each SCCmec type, but certain J regions are commonly shared among certain types of SCCmec elements. Of the three regions, we regard J1 as the most fundamental, because we presume that it reflects the original form of SCC into which a mec gene complex have been integrated. Moreover, several different J1 regions have been identified in type-II and type-IV SCCmec elements. The presence or absence of integrated plasmids encoding drug resistance genes in the J3 regions of SCCmec elements can also be used as markers to classify SCCmec elements further in epidemiological studies.
The subtypes of type-II and type-IV SCCmec elements would be described in alphabet or in numerals in the order that they are found, as follows (the naming system will be established soon): type II.1 or IIa, type II.2 or IIb, type IV.1 or IVa, type IV.2 or IVb, type IV.3 or IVc, and type IV.4 and IVd.
Illustrations of SCCmec elements that link to data bases.
Please click SCCmec Type to see detailed structure of the element or to see subtypes of each SCCmec type.
The short history for naming of the SCCmec types.
In 2001, Oliveira et al. identified a pediatric strain, HDE288, which carried novel SCCmec, of which ccr genes were not identical to three previously reported ccr genes, and designated the element as type-IV SCCmec（Oliveira et al, 2001）. Independently, Ma et al. have identified SCCmec elements carrying class B mec gene complex and type-2 ccr gene complex in CA-MRSA strains, CA05 and 8/6-3P, which were isolated at the University of Chicago Children’s Hospital, and designated these type-IV SCCmec (Ma et al., 2002). To solve the confusion of the naming, we proposed new nomenclatural system describing SCCmec types by ccr type (indicated by a number) and mec class (indicated by an uppercase letter), e.g., 2A, and difference in J regions in numbers. If the proposed nomenclature were adopted, the type-IV SCCmec element found in HD288 would be called type-4B, signifying that the element carried type-4 ccr (fourthly identified ccr) and class B mec and those found in CA05 and 8/6-3P would be called 2B signifying that the element carried type-2 ccr and class B mec. However, many researchers wished to retaining the use of Roman numeral for description of SCCmec type, Roman numerals are used for describing SCCmec types, and proposed naming system are used as bases for the typing.
The mec gene complex
The expression of mecA gene is regulated by two proteins, MecI (a repressor protein) and MecR1 (a signal transducer protein). When MecI binds to the promoter region of mecA, the transcription of mecA is repressed. If β-lactam antibiotics bind to MecR1, the polypeptide having protease activity released from the MecR1 to degrade MecI, resulting to the increase of the transcription of mecA. Both two genes, mecI and mecR1, locate upstream of mecA. However, these two genes were sometimes deleted or truncated, most of which were caused by the integration of insertion sequences, IS431 or IS1272. An insertion sequence IS431 was located downstream of mecA. We regard the gene allele as mec gene complex, which is composed of mecA, its regulatory genes, mecI and mecR1, and insertion sequence IS431 located at the downstream of mecA. Five classes of mec gene complex have been reported as follows (Antimicrob. Agents Chemother: 2009 vol. 53 no. 12 4961-4967)
classes mec gene complexes
D IS431-mecA-ΔmecR1 (no insertion sequence was identified so far tested by long-range PCR)
The ccr gene complex
The ccr gene complex is composed of one or two site-specific recombinase genes, which are responsible for the mobility of SCCmec, and surrounding orfs of unknown function. The ccr genes can catalyze precise excision and site- and orientation- specific integration of SCCmec elements. Four allotypes of ccrA, B genes have been reported. They were ccrA1 and ccrB1 (carried by type-I SCCmec ), ccrA2 and ccrB2 (carried by type-II SCCmec ), ccrA3 and ccrB3 (carried by type-III SCCmec), and ccrA4 and ccrB4 (carried by type-IV SCCmec). In addition, a ccr gene designated ccrC was identified in the type-V SCCmec element or SCC element e.g., SCCmercury. All Ccr proteins (CcrA, CcrB, and CcrC) have a catalytic motif at the N-terminal domain, which is characteristic for recombinases of the invertase/resolvase family. They were basic proteins with PI values of 9.68-9.85. The figure below illustrates the phylogenetic relations of ccr genes, and other site-specific recombinase genes such as the integrase of Enterococcus faecalis Bacteriophagee phi-FC1 and site-specific recombinase of Clostridium acetobutylicum ATCC824. In order to investigate the phylogenetic relations of those ccr genes, we reconstituted the putative ccrB1 (ccrB1*) and ccrB4 (ccrB4*) of 1629 bp in size by adding back an adenine to the deletion point of the truncated ccrB1 and ccrB4 gene, since ccrB1 of NCTC10442 and ccrB4 of HDE288 is truncated. Phylogenetic tree showed that each ccr gene constituted a group of ccr genes, which was distinct from other ccr genes.
ISS (Integration site sequence of SCCmec)
Characteristic nucleotides at both ends, direct repeats (DR) and inverted repeats (IR), are located at both ends. They might work as recognition sites of ccr genes.
On the description of the SCCmec types.
We proposed a new nomenclatural system for SCCmec elements that has three features. The first feature is a description of SCCmec type. A SCCmec element can be simply described by ccr type (indicated by a number) and mec class (indicated by an uppercase letter). Alternatively, Roman numeral designations can be used instead of combinations of ccr and mec（Chongtrakool et al. 2006）. We retained Roman numeral to describe SCCmec type as feedback from a large number of researchers who told us that they were convenient and well established. We have developed a new nomenclature for SCCmec types, which is an attempt to resolve confusion in the field and to facilitate the identification of novel SCCmec elements. In 2001, Oliveira et al. reported the a pediatric strain, HDE288, carried novel SCCmec element of which ccr genes were not identical to three previously reported ccr genes, and designated the new SCCmec element as type-IV SCCmec（Oliveira et al, 2001）. Independently, Ma et al. have found SCCmec elements carrying class B mec and type-2 ccr in C-MRSA strains, which were isolated at the
The description of J regions has been modified from our original proposal in line with the suggestions from Dr. Kunyan Zhang (University of