MECHANISTIC LINK BETWEEN UPTAKE OF SULFONAMIDES AND BACTERIOSTATIC EFFECT: MODEL DEVELOPMENT AND APPLICATION TO EXPERIMENTAL DATA FROM TWO SOIL MICROORGANISMS

Autor(en): Focks, Andreas 
Klasmeier, Joerg 
Matthies, Michael
Stichwörter: ANTIBIOTICS; DIHYDROPTEROATE SYNTHASE; Dose-response relationship; Effect model; Environmental Sciences; Environmental Sciences & Ecology; ESCHERICHIA-COLI; GROWTH; INDUCED COMMUNITY TOLERANCE; MANURE; MICROBIAL ACTIVITY; PH; pH Dependence; RESISTANCE; Soil microbes; SULFADIAZINE; Sulfonamides; Toxicology
Erscheinungsdatum: 2010
Herausgeber: SETAC PRESS
Journal: ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
Volumen: 29
Ausgabe: 7
Startseite: 1445
Seitenende: 1452
Zusammenfassung: 
Sulfonamides (SA) are antibiotic compounds that are widely used as human and veterinary pharmaceuticals. They are not rapidly biodegradable and have been detected in various environmental compartments. Effects of sulfonamides on microbial endpoints in soil have been reported from laboratory incubation studies. Sulfonamides inhibit the growth of sensitive microorganisms by competitive binding to the dihydropteroate-synthase (DHPS) enzyme of folic acid production. A mathematical model was developed that relates the extracellular SA concentration to the inhibition of the relative bacterial growth rate. Two factors-the anionic accumulation factor (AAF) and the cellular affinity factor (CAF)-determine the effective concentration of an SA. The AAF describes the SA uptake into bacterial cells and varies with both the extra- and intracellular pH values and with the acidic pK(a) value of an SA. The CAF subsumes relevant cellular and enzyme properties, and is directly proportional to the DHPS affinity constant for an SA. Based on the model, a mechanistic dose-response relationship is developed and evaluated against previously published data, where differences in the responses of Pseudomonas aeruginosa and Panthoea agglomerans toward changing medium pH values were found, most likely as a result of their diverse pH regulation. The derived dose response relationship explains the pH and pK(a) dependency of mean effective concentration values (EC50) of eight SA and two soil bacteria based on AAF and CAF values. The mathematical model can be used to extrapolate sulfonamide effects to other pH values and to calculate the CAF as a pH-independent measure for the SA effects on microbial growth. Environ. Toxicol. Chem. 2010;29:1445-1452. (C) 2010 SETAC
ISSN: 07307268
DOI: 10.1002/etc.172

Show full item record

Page view(s)

1
Last Week
0
Last month
0
checked on Apr 13, 2024

Google ScholarTM

Check

Altmetric