It isfor the most part accepted that B lactamases are overwhelmingly responsible forthe protection from penicillin in strains of S. aureus. Moreover, a strongrelationship between the measure of enzyme produced and the subsequent level ofresistance has not been affirmed, even found that some strains of S. aureuswere defenseless to penicillin G at concentrations of 0.05 mg/L or less inspiteproducing B lactamase.
According to the findings in current studies, there was adiscrete correlation between induced B-lactamase synthesis by staphylococcalstrains from different sources and their irresponsiveness to penicillin G and ampicillin;the more the measure of partially excreted B lactamase in the surrounding along with antibiotic induction the increasein the level of resistance will occur thereby, it inactivates the penicillinmaking them unable to reach their target site i.e. cytoplasmic membrane. It hasbeen considered that more than 80% of the B lactamase is normally excreted fromthe cells Moreover; different strains release different diverse quantitydepending, mainly on development conditions.
One specific strain of S. aureusreleases more than 1% but this is a very rare exception. During the researchstudies conducted in Pharmacokinetics department of Germany it has been foundthat most of the strains showed intermediate characteristics that is fiftypercent of the strains produced beta lactamase upon induction with penicillin Gand ampicilllin whereas, uninduced strains shows 40% of extracellular betalactamase excretion. When the staphylococcal strains were induced withprolonged methicillin the response was heterogeneous; 20% and 50% variationoccurred in beta lactamase excretion irrelevant to the total amountsynthesized. Some strain has produced the greatest amount of beta lactamsae butexcretes the least. In staphylococcusaureus and in other gram-positive bacteria, have cytoplasmic membrane withfirmly bound intracellular B lactamase.These studies may help in determining the importance of extracellular B lactamaseresistance in vitro but these findings may not be applicable or same in vivo.
Diffusionby diluting the environment is an option to reduce produced beta lactamase or otherways to reduce their effectiveness include certain tissue factors, e.g. Dropped pH values in inflamed areas, proteasesaction, oxygen radical’s production during phagocytosis or antibody productionwhich leads to inactivation.
The second line of defense is provided by themembrane bound beta lactamase, the close proximity of membrane bound betalactamase to the target site of penicillin leads to increase effectiveness. Thiswhole scenario view was supported by the descriptive studies that are bindingof 14C-penicillin G with cell membranes of staphylococcus aureus. The bindingof penicillin with membrane of resistant strain was non-specific only, but uponclavulinic acid induction it would first inhibited and a notable enhancement inbinding of penicillin to membrane was observed eventually, staphylococci showsusceptible. The uninduced membranes of cells specifically would not bind14C-penicillin G but, after induction, approximately tenfold increase theproduction of membrane-bound B lactamase eventually increasing its defensive property.
Indifferent studies it has been set out that production of intracellular Blactamase was unable to protect staphylococci from mezlocillin given in higherconcentrations, this leads in achievement of susceptibility in resistant strain.Moreover, it is still not explicit from experiments how much beta lactamase wasbeing synthesized in the presence mezlocillin nor the intra- and extracellular distributionof enzyme. From the consequences of the presentinvestigation, it can be closed, in any case, that in staphylococci B lactamaseconstitutes a twofold boundary similar to that found in gram-negativemicroorganisms; the external layer, framed by extracellular B lactamase,typically inactivates a large portion of the penicillin before can penetratethe cells, while membrane bound Blactamase acts for possible later use, ensuring the bacterial cells when theextracellular protection, for whatever reasons, is deficient.