Community Associated Methicillin-Resistant Staphylococcus Aureus: A Review

Michael J. Rybak, PharmD; Kerry L. LaPlante, PharmD

Disclosures

Pharmacotherapy. 2005;25(1):74-85. 

In This Article

Molecular Analysis of Community - and Health Care - Associated MRSA

Several investigations have explored the molecular aspects of CA-MRSA. One research group investigated the potential for a shared common origin of HA-MRSA and CA-MRSA.[38] Twenty-three well characterized strains of CA-MRSA were compared with 12 non-multidrug-resistant, oxacillin-resistant S. aureus (NORSA) strains—strains that are frequently isolated in hospitals but are considered to be decedents of CA-MRSA isolates—and with representative hospital isolates. Most but not all of the CA-MRSA strains were susceptible to a variety of non-β-lactams, as was generally the case with NORSA isolates. This indicated that CA-MRSA strains can acquire resistance to non-β-lactams through exposure. The CA-MRSA strains were also found to have lower levels of resistance to oxacillin and imipenem-cilastatin (minimum inhibitory concentrations of 8-32 µg/ml), implying that CA-MRSA strains, unlike HA-MRSA strains, were not selected by exposure to the potent β-lactam agents typically used in hospital settings. It was also observed that doubling times were significantly shorter for CA-MRSA than for HA-MRSA. The authors speculated that this high growth rate may help CA-MRSA achieve successful colonization by enabling it to outcompete other bacterial species that are normally part of the commensal flora.

Application of multilocus sequence typing and evolutionary mathematical models to an international collection of 359 MRSA isolates has revealed that all MRSAs share a common genetic lineage and can be traced to a single MRSA clone. This strain, known as ST-250, appears to have evolved from a methicillin-susceptible S. aureus (MSSA) isolate, which subsequently acquired the mec gene from an unknown source. Minor variations of this organism, such as ST-247; the Iberian clone; and ST-5, 22, and 45, have evolved into some of the more common MRSA isolates that have been found around the world. The diversity of MRSA strains is secondary to horizontal transfer of genetic elements that insert into the bacterial genome. Current MRSA isolates are either descendants of preexisting clones or have been created by horizontal transfer of the mec determinant into successful MSSA.[39] The mecA gene in staphylococci is responsible for β-lactam resistance. This gene encodes a penicillin-binding protein that has low affinity for β-lactam-type antibiotics. The mecA gene complex is carried on a specific integrative genetic element known as the staphylococcal cassette chromosome (SCC). These mobile cassettes consist of the mec complex and the cassette recombinase genes, which are responsible for encoding integration and excision of the SCCmec element on the staphylococcal chromo-some (Figure 1).

Structure of the staphylococcal cassette chromosome mec, with the recombinase genes complex upstream of the mec complex. The mec complex contains the mecA gene responsible for β-lactam resistance in Staphylococcus aureus. IS1272 = insertion sequence-like element; ccrA and ccrB = cassette chromosome recombinase genes A and B that mobilize the mec element; mecR1 = mec sensor transducer and repressor genes that regulate production of PBP-2A, which is responsible for β-lactam resistance; IS431 = integrated plasmid that encodes tetracycline resistance; and orfx = open reading frame in which the mobile elements (staphylococcal cassette chromosome) are located. (Adapted in part from reference 37.)

Five SCCmec types have been identified for S. aureus. The gene elements differ in size, composition, and associated antimicrobial resistance expression ( Table 1 ).[40,41,42] The SCCmec types I, II, and III are found predominately in HA-MRSA isolates. These isolates carry a number of inserted plasmids and transposable genetic elements downstream of the mecA complex. The SCCmec types II and III are responsible for the multiple non-β-lactam antimicrobial resistance often expressed in these health care-related strains. The SCCmec type IV is typically found in CA-MRSA strains and in NORSA isolates. This SCCmec type is smaller in size and lacks other multidrug-resistance genes. Recently, a SCCmec type V was described. Similar to type IV, it is small in size, does not contain antimicrobial resistance genes other than mecA, and is found predominately in CA-MRSA and NORSA strains.[40]

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