Polyoxotungstates Reduce the β-Lactam Resistance of Methicillin-Resistant Staphylococcus aureus

Abstract

Bacterial strains isolated from clinical specimens have become more and more resistant to many anti-microbials. This is because we have consumed large amounts of strong antimicrobials over long periods of time and thus bacterial cells are able to survive by altering the target(s) of antimicrobial agents. A good example of this phenomenon is methicillin-resistant Staphylococcus aureus (MRSA). One of the cell wall-synthesizing enzymes (known as PBP2') of this pathogen has low affinity to beta-lactams, and therefore the bacterial cells continue to grow even under high concentrations of the agents. However, this drug resistance does not seem to be total. They seem to have some weak spots and several substances are known to sensitize strains of MRSA to beta-lactams. This review discusses the ability of polyoxotungstates (POTs) to sensitize MRSA to beta-lactams by reducing the expression of PBP2'. It is also possible that the sensitization is a type of stress response of MRSA to POTs. This idea may provide a hint for the development of a new antimicrobial agent.

Alternative therapies in Staphylococcus aureus diseases.

“…The mechanism responsible for this phenomenon is probably the stress response of MRSA to POT. Sensitization to beta-lactams was also seen with other substances such as fosfomycin, Triton X-100, tannin and some flavonoids (Tajima, 2005).…”

Synthesis and Antibacterial Activity of Polyoxometalates with Different Structures

“…Polyoxometalates (POMs) have been shown to exhibit biological activities in vitro as well as in vivo , including anticancer and antiviral [1], antibacterial [2, 3], antiprotozoal [4, 5], and antidiabetic activities [6]. In the antibacterial activity study of POMs, Tajima found the enhancement of several beta-lactams antibiotics in antibacterial activity to methicillin-resistant Staphylococcus aureus under the synergistic action of polyoxometalates, substituted-type POMs K 7 [PTi 2 W 10 O 40 ] 6H 2 O, K 7 [BVW 11 O 40 ]7H 2 O, [SiFeW 11 O 40 ] 6/5− and [SiCoW 11 O 40 ] 6− and lacunary-type POMs [XW 11 O 39 ] n− (X = Si, P) and [XW 9 O 34 ] n− , and proposed the resistant mechanism [7–12]. Inoue et al reported the enhancement of antibacterial activity of beta-lactam antibiotics, oxacillin, by polyoxometalates (K 6 [P 2 W 18 18O 62 ]·14H 2 O, K 4 [SiMo 12 O 40 ]·3H 2 O, and K 7 [PTi 2 W 10 O 40 ]·6H 2 O) against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) and also proposed a reaction mechanism [13].…”

Prenatal exposure of mice to tungstate is associated with decreased transcriptome-expression of the putative tumor suppressor gene, DMBT1: implications for childhood leukemia

“…These physiological effects associated with phosphorous-POTs include inhibition of factors IIa and Xa in the presence of anti-thrombin III and inhibition of anion-transport in erythrocytes and porcine sperm. The WO 4 2ion did not exhibit these traits (reviewed in Tajima 2005).…”