A Factor Found in Aged Tungstate Solution Enhanced the Antibacterial Effect of β‐Lactams on Methicillin‐Resistant Staphylococcus aureus

Abstract

We have found a factor (Factor T) in aged mixtures of tungstate and phosphate which greatly enhances the antibacterial effects of β‐lactams on both inducible and constitutive methicillin‐resistant Staphylococcus aureus, but not on methicillin‐susceptible S. aureus. Factor T alone did not strongly inhibit bacterial growth. There was no synergism of Factor T with other classes of antibiotics, nor with other groups of bacteria, and it reduced the efficacy of aminoglycosides and tetracycline. Upon preparation of Factor T, acidifying and heating the mixture of tungstate and phosphate resulted in a high yield and reproducibility, and no enhancing effect was observed when other anions such as sulfate or molybdate were used instead. Factor T is heat‐ and acid‐stable but labile to alkalization, and is probably a complex of phosphate and tungstate.

Lacunary-Substituted Undecatungstosilicates Sensitize Methicillin-Resistant Staphylococcus aureus to .BETA.-Lactams.

“…2,10) Therefore, polyoxotungstates had a weak sensitizing effect on methicillin-susceptible S. aureus (MSSA) strain (Table 3), but this might not be obvious in the "Enhancement Index" because b-lactams acted strongly on such strains even before sensitization by the polyoxotungstates. 1,2) Probably for the same reason, MICs of b-lactams were minimized even in MRSA strains and sometimes reduced below the lower measurement limits (Tables 1 and 3).…”

“…Furthermore, there was no synergism of the polyoxotungstates with other classes of antibiotics including vancomycin and teicoplanin (both inhibitors of cell wall synthesis, like b-lactams 20) ), and there was no effect against bacterial strains other than staphylococcal species. 1,2) Although the mechanism of action of polyoxotungstates has not been completely elucidated, they seem to reduce the expression of penicillin-binding proteins (PBPs), thereby making MRSA strains greatly susceptible to b-lactams. These compounds neither directly inactivated PBPs nor increased in their affinities for b-lactams.…”

“…The other chemicals, culture media, established bacterial strains used in this study, and the method of preparing PW 11 are described in our previous reports. 1,2,11) Medium pH was kept at pH 7.0Ϯ0.1 to avoid decomposition of the polyoxotungstates. Although all the tungsten compounds used in the experiments are heat-stable, WO 4 2Ϫ and/or SiO 3 2Ϫ were mixed with the agar medium below about 45°C.…”

Antibacterial activity of some saturated polyoxotungstates

“…The antibacterial activity of compounds with Keggin structures on MRSA was studied before for the synergistic effect of POMs in combination with β-lactamic antibiotics (2,8,18,23,32). In this paper, we studied the antibacterial activity of POM compounds as drugs themselves.…”

“…POMs' catalytic properties were described by Papaconstantinou and Mylonas in water decontamination of aliphatic and aromatic representative compounds (14) (16)(17)(18). POM antiviral and antitumoral efficacy, as well as insulin-mimetic activity (19), were shown in vitro and in vivo.…”