Colistin has been regarded as the last line antibiotic for treatment of infections caused by multidrug resistant gram-negative bacteria. Therefore, the increasing emergence of colistin resistance among gram-negative b...Colistin has been regarded as the last line antibiotic for treatment of infections caused by multidrug resistant gram-negative bacteria. Therefore, the increasing emergence of colistin resistance among gram-negative bacteria represents a serious problem. The objective of this study was to characterize the effectiveness of the chemically synthesized thanatin in linear form against colistin-resistant E. coli isolated from a pig farm in China. Agar diffusion assay and broth microdilution test were employed to analyze the susceptibility of colistin-sensitive E. coli (ATCC25922) and colistin-resistant E. coli (SHP45) to linear thanatin (L-thanatin). Combinatory effect of linear thanatin and colistin against E. coli was also determined by fractional inhibition concentration index (FICI) analysis. The results showed that L-thanatin at a concentration of 1 mg/ml produced larger inhibition zone on agar against ATCC25922 than SHP45. In the quantitative microdilution test, L-thanatin had the same MIC of 3.2 μg/ml for ATCC25922 and SHP45. Based on the FICI analysis, additive effect was obtained with 1.56 μg/ml of L-thanatin and 0.125 μg/ml of colistin for ATCC25922;but with 1.56 μg/ml of L-thanatin and 0.25 μg/ml of colistin or with 2 μg/ml of colistin and 0.39 μg/ml of L-thanatin for SHP45. These data proved that L-thanatin is an effective antimicrobial peptide against colistin-resistant E. coli.展开更多
In this work, the role of the disulfide bridges in the maintenance of the secondary structure of the antimicrobial peptides androctonin, poly-phemusin-I, and thanatin is analyzed on the basis of their structural chara...In this work, the role of the disulfide bridges in the maintenance of the secondary structure of the antimicrobial peptides androctonin, poly-phemusin-I, and thanatin is analyzed on the basis of their structural characteristics and of three of their respective mutants, andry4, poly4, and thany2, in which all the cysteine residues have been replaced with tyrosine residues. The absence of the disulfide bridges in andry4, poly4, and thany2 seems to be compensated by an overall enforcement of the original hydrogen bonds and by extra attractive interactions between the aromatic rings of the tyrosine residues. In spite of the mutations, the original β-hairpin structures are maintained in the three mutants, but the best conformational similarities are found for the androctonin/andry4 pair.展开更多
文摘Colistin has been regarded as the last line antibiotic for treatment of infections caused by multidrug resistant gram-negative bacteria. Therefore, the increasing emergence of colistin resistance among gram-negative bacteria represents a serious problem. The objective of this study was to characterize the effectiveness of the chemically synthesized thanatin in linear form against colistin-resistant E. coli isolated from a pig farm in China. Agar diffusion assay and broth microdilution test were employed to analyze the susceptibility of colistin-sensitive E. coli (ATCC25922) and colistin-resistant E. coli (SHP45) to linear thanatin (L-thanatin). Combinatory effect of linear thanatin and colistin against E. coli was also determined by fractional inhibition concentration index (FICI) analysis. The results showed that L-thanatin at a concentration of 1 mg/ml produced larger inhibition zone on agar against ATCC25922 than SHP45. In the quantitative microdilution test, L-thanatin had the same MIC of 3.2 μg/ml for ATCC25922 and SHP45. Based on the FICI analysis, additive effect was obtained with 1.56 μg/ml of L-thanatin and 0.125 μg/ml of colistin for ATCC25922;but with 1.56 μg/ml of L-thanatin and 0.25 μg/ml of colistin or with 2 μg/ml of colistin and 0.39 μg/ml of L-thanatin for SHP45. These data proved that L-thanatin is an effective antimicrobial peptide against colistin-resistant E. coli.
基金Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP)for financial support.
文摘In this work, the role of the disulfide bridges in the maintenance of the secondary structure of the antimicrobial peptides androctonin, poly-phemusin-I, and thanatin is analyzed on the basis of their structural characteristics and of three of their respective mutants, andry4, poly4, and thany2, in which all the cysteine residues have been replaced with tyrosine residues. The absence of the disulfide bridges in andry4, poly4, and thany2 seems to be compensated by an overall enforcement of the original hydrogen bonds and by extra attractive interactions between the aromatic rings of the tyrosine residues. In spite of the mutations, the original β-hairpin structures are maintained in the three mutants, but the best conformational similarities are found for the androctonin/andry4 pair.
