POSSIBLE MECHANISM OF ACTION OF BETA-LACTAM-ENHANCING FACTOR ON METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS

We have recently found a factor (Factor T) in aged mixtures of tungsta te and phosphate which greatly enhances the antibacterial effects of b eta-lactams on methicillin-resistant strains of staphylococcal species such as methicillin-resistant Staphylococcus aureus (MRSA), but shows only weak effects on methicillin-susceptible S.aureus and bacterial s trains other than staphylococci. Factor T alone did not strongly inhib it cell metabolism and bacterial growth unless an excess amount was ad ded. When Factor T was added to the culture medium beforehand, the gro wth of MRSA cells was rapidly suppressed just after addition of oxacil lin (MPIPC). However, the growth of the cells was inhibited gradually when these two reagents were added in reverse order. For full expressi on of the enhancing effect, it seemed necessary for cells of MRSA stra ins to be incubated with Factor T for at least 2-3 hr. When the cells were washed after being sensitized by incubating them for 5 hr with Fa ctor T, it took approximately 1 hr for the cells to recover their resi stance to MPIPC. Factor T reduced the amount of penicillin-binding pro tein-2' (PBP 2'), and thus sensitized the MRSA strains to beta-lactams .