This enables transpeptidase activity in the presence of beta-lactams, preventing them from inhibiting cell wall synthesis.
[5][6] Researchers traced the source of this resistance to the mecA gene acquired through a mobile genetic element, staphylococcal cassette chromosome mec, present in all known MRSA strains.
[15] The S. aureus strains isolated from humans either lack these regulatory elements or contain mutations in these genes that cause a loss of function of the protein products that inhibit mecA.
Two other Staphylococci species, S.epidermidis and S.haemolyticus, show conservation in this insertion site, not only for mecA but also for other non-essential genes the cassette chromosome can carry.
[17] Penicillin, its derivatives and methicillin, and other beta-lactam antibiotics inhibits activity of the cell-wall forming penicillin-binding protein family (PBP 1, 2, 3 and 4).
[19] When antibiotics enter the medium, they bind to the transpeptidation domain and inhibit PBPs from cross-linking muropeptides, therefore preventing the formation of stable cell wall.
With cooperative action, PBP2a lacks the proper receptor for the antibiotics and continues transpeptidation, preventing cell wall breakdown.
[21] Second, PBP2a has an effective transpeptidase activity but lacks the transglycosylation domain of PBP2, which builds the backbone of the cell wall with polysaccharide monomers, so PBP2a must rely on PBP2 to continue this process.
[21][20] The latter forms a therapeutic target to improve the ability of beta-lactams to prevent cell wall synthesis in resistant S. aureus.
Identifying inhibitors of glycosylases involved in the cell wall synthesis and modulating their expression can resensitize these previously resistant bacteria to beta-lactam treatment.
[22] For example, epicatechin gallate, a compound found in green tea, has shown signs of lowering the resistance to beta-lactams, to the point where oxacillin, which acts on PBP2 and PBP2a, effectively inhibits cell wall formation.