Evaluation of the antimicrobial activity of methylglyoxal bis(guanylhydrazone) analogues, the inhibitors for polyamine biosynthetic pathway

Abstract

Metabolic and antiproliferative effects of methylglyoxal bis(butylamidinohydrazone) (MGBB) and methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), inhibitors for polyamine biosynthetic pathway, on Escherichia coli, Shigella sonnei, Aeromonas sobria, Aeromonas hydrophila and Vibrio cholerae were investigated. MGBB at the concentration of 100 mumol/l depleted intracellular putrescine and spermidine concentrations of E. coli to 25 and 20% of the controls, respectively, while MGBCP depressed their concentrations to 38 and 24%, respectively. In these polyamine-depleted E. coli cells the syntheses of RNA, DNA and protein decreased to 13, 54 and 29% of the control, respectively, with MGBB and to 23, 71 and 55%, respectively, with MGBCP. The minimum inhibitory concentrations (MIC) of MGBB for the growth of A. sobria, E. coli, A. hydrophila, V. cholerae and Sh. sonnei were estimated to be 50, 160, 240, 285 and 320 mumol/l, respectively, whereas those of MGBCP were slightly higher for respective bacteria.

Pseudomonas aeruginosa glutathione biosynthesis genes play multiple roles in stress protection, bacterial virulence and biofilm formation

“…Then, dihydroxyacetone phosphate (DHAP, a glycolysis intermediate) could be converted to methylglyoxal by methylglyoxal synthase [ 23 , 26 ]. Methylglyoxal uses different mechanisms to exert its antimicrobial activity, including inhibition of protein, DNA, and RNA synthesis [ 27 , 28 ]. Bacterial methylglyoxal detoxification is carried out mainly by glyoxalase I and II enzymes [ 23 ].…”

Polymer based nanoformulation of methylglyoxal as an antimicrobial agent: efficacy against resistant bacteria

“…55 Highly reactive dicarbonyls of MG can attack the lysine, arginine (Arg) and cysteine residues of proteins and also DNA synthesis. 56 It can be assumed that NMG directly inhibits a specic respiratory enzyme or metabolic pathway via the oxidation of the reducing cellular energy carriers like NADH and NADPH (Fig. 4) and leakage of potassium ions commenced upon exposure of NMG may alter cell membrane structure.…”

Metilglioxal: uma toxina endógena?

“…Quando adicionado a culturas de E. coli, o metilglioxal causou diminuição da síntese de RNA e DNA bem como depleção de espermidina e putrescina de E. coli, como esperado, pois estas poliaminas são vitais à proliferação e são desativadas por adição ao metilglioxal. 159 Metilglioxal também se mostrou tóxico quando administrado a culturas de Prevotella ruminicola, uma bactéria encontrada em ruminantes, quando crescida em meio enriquecido de glicose (50 mM). 160 Esta resposta foi atribuída ao estresse oxidativo desencadeado por metilglioxal devido ao consumo excessivo de glutationa (GSH).…”