Reversal of the Antibacterial Activity of Polymyxin by Divalent Cations

Newton, B.A.

doi:10.1038/172160a0

Cited by 70 publications

(45 citation statements)

References 4 publications

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“…Like the aminoglycosides, the effect seemed to be on the uptake of drug or on the interaction of the cations with the cell wall (2,12,13). In one report, the antagonistic effect was less than that observed with gentamicin (8), whereas in another it was greater (5), and in a third variable (3).…”

Section: Discussionmentioning

confidence: 99%

“…The antagonistic effect of divalent cations on the antibacterial activity of aminoglycosides (7), polymyxins (12), and tetracycline (18) has been recognized for many years. The largest number of reports (1, 3,5,8,9,11,15,19) have documented the marked effects of the calcium and magnesium content in broth media on the activity of gentamicin against Pseudomonas aeruginosa but not Enterobacteriaceae.…”

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confidence: 99%

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Effect of Divalent Cation Concentrations on the Antibiotic Susceptibilities of Nonfermenters Other than Pseudomonas aeruginosa

Fass

Barnishan

1979

Antimicrob Agents Chemother

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The effects of supplementing Mueller-Hinton broth with calcium and magnesium on the miniimal inhibitory concentrations (MICs) of eight aminoglycosides, colistin, tetracycline, and carbenicillin for 11 nonfermenters other than Pseudomonas aeruginosa were studied and compared with the effects for Escherichia coli and P. aeruginosa. MICs were simultaneously performed in unsupplemented MuellerHinton broth and Mueller-Hinton broth supplemented to contain 5 mg of calcium and 2.5 mg of magnesium per dl. Changes in MICs were expressed as the increases in the number of log2 concentrations caused by supplementation. The usual increases in MICs of aminoglycosides caused by supplementation were: zero concentrations for E. coli, one to six concentrations for P. aeruginosa, and one to two concentrations for most other nonfermenters. The largest increases (five to six concentrations) were observed with gentamicin and P. aeruginosa. The usual increases in MICs of colistin were: zero concentrations for E. coli, two concentrations for P. aeruginosa, and one to two concentrations for other nonfermenters. Increases in MICs of tetracycline were: one to five concentrations for all organisms tested. The usual increases in MICs of carbenicillin were: zero concentrations for E. coli and P. aeruginosa and zero to two concentrations for other nonfermenters. These observations indicated that supplementation of Mueller-Hinton broth to contain recommended concentrations of calcium and magnesium had little effect on MICs of aminoglycosides and colistin for E. coli but increased MICs for most nonfermenters, increased MICs of tetracycline for E. coli and all nonfermenters, and had little effect on MICs of carbenicillin for E. coli and P. aeruginosa but increased the MICs for several nonfermenters other than P. aeruginosa.The antagonistic effect of divalent cations on the antibacterial activity of aminoglycosides (7), polymyxins (12), and tetracycline (18) has been recognized for many years. The largest number of reports (1,3,5,8,9,11,15,19) have documented the marked effects of the calcium and magnesium content in broth media on the activity of gentamicin against Pseudomonas aeruginosa but not Enterobacteriaceae. Because commercially available media vary considerably in their calcium and magnesium contents (8,9,11,15,17), it has been recommended that susceptibility testing by broth dilution techniques utilize Mueller-Hinton broth (MHB), a medium low in calcium and magnesium content, which is supplemented to contain physiological condentrations of those cations (3,9,15,16).This study was designed to determine the effects of supplementing MHB with calcium and magnesium on the in vitro activities of eight aminoglycoside antibiotics, colistin, and tetracycline against nonfermenters other than P. aeruginosa; strains of Escherichia coli and P. aeruginosa were included for comparison. Carbenicillin, an antibiotic active against P. aeruginosa, but not markedly affected by calcium and magnesium (3,5,15,19)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of Divalent Cation Concentrations on the Antibiotic Susceptibilities of Nonfermenters Other than Pseudomonas aeruginosa

Fass

Barnishan

1979

Antimicrob Agents Chemother

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“…However, a cation-dependent inhibition of antimicrobial activity has been reported for polymyxin antibiotics (90,91). In fact, it is suspected that the colistin antimicrobial activity might be overestimated if tested using conventional cation-adjusted MH as recommended by the CLSI.…”

Section: Impact Of Materials On Mic Determinationmentioning

confidence: 99%

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

2017

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SUMMARY Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.

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“…The polar head and nonpolar fatty acid chain confer amphipathic properties which permit the polymyxins to interact with both lipopolysaccharides and phospholipids (18,36,37,48). Furthermore, polymyxins also interact electrostatically with membranes in the gram-negative cell envelope by competitively displacing divalent cations (e.g., calcium and magnesium) from the negatively charged phosphate groups of membrane lipids (26). Disruption of the divalent cation bridges and insertion of the cyclic ring (heptapeptide) into the membrane bilayer are likely to be responsible for the observed destabilization of membrane integrity induced by polymyxins (36).…”

mentioning

confidence: 99%

Leakage of periplasmic proteins from Escherichia coli mediated by polymyxin B nonapeptide

Dixon¹,

Chopra²

1986

Antimicrob Agents Chemother

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The effects of polymyxin B and polymyxin B nonapeptide (PMBN) on cell envelope integrity in Escherichia coli were compared. Both compounds caused loss of proteins from E. coli K-12 3300(pBR322), although PMBN released less protein than did polymyxin B. The origin of the released protein was determined both by polyacrylamide gel electrophoresis and by using specific enzyme markers (beta-lactamase in periplasm, beta-galactosidase in cytoplasm). The proteins released by both compounds were derived principally from the periplasm, accompanied in the case of polymyxin B by a low level of cytoplasmic proteins. Although polymyxin B and PMBN both caused release of periplasmic proteins, the individual proteins released by the compounds differed. The periplasmic fraction contained six principal polypeptides with molecular weights between 62,000 (polypeptide 1) and 29,000 (polypeptide 6). Polypeptide 6 was identified as the pBR322-encoded betalactamase, but the other proteins were not specifically identified. Polymyxin B caused considerable release of polypeptides 1, 2, and 5 with some release of polypeptides 4 and 6. PMBN released polypeptide 1 (trace), 3, 4, and 6 (trace). Scanning electron microscopy showed that polymyxin B and PMBN both caused surface damage in E. coli. However, polymyxin B produced greater morphological changes than PMBN.

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Reversal of the Antibacterial Activity of Polymyxin by Divalent Cations

Cited by 70 publications

References 4 publications

Effect of Divalent Cation Concentrations on the Antibiotic Susceptibilities of Nonfermenters Other than Pseudomonas aeruginosa

Effect of Divalent Cation Concentrations on the Antibiotic Susceptibilities of Nonfermenters Other than Pseudomonas aeruginosa

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

Leakage of periplasmic proteins from Escherichia coli mediated by polymyxin B nonapeptide

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