Biphasic toxicodynamic features of some antimicrobial agents on microbial growth: a dynamic mathematical model and its implications on hormesis.
BACKGROUND
In the present work, we describe a group of anomalous dose-response (DR) profiles and develop a dynamic model that is able to explain them. Responses were obtained from conventional assays of three antimicrobial agents (nisin, pediocin and phenol) against two microorganisms (Carnobacterium piscicola and Leuconostoc mesenteroides).


RESULTS
Some of these anomalous profiles show biphasic trends which are usually attributed to hormetic responses. But they can also be explained as the result of the time-course of the response from a microbial population with a bimodal distribution of sensitivity to an effector, and there is evidence suggesting this last origin. In light of interest in the hormetic phenomenology and the possibility of confusing it with other phenomena, especially in the bioassay of complex materials we try to define some criteria which allow us to distinguish between sensu stricto hormesis and biphasic responses due to other causes. Finally, we discuss some problems concerning the metric of the dose in connection with the exposure time, and we make a cautionary suggestion about the use of bacteriocins as antimicrobial agents.


CONCLUSIONS
The mathematical model proposed, which combines the basis of DR theory with microbial growth kinetics, can generate and explain all types of anomalous experimental profiles. These profiles could also be described in a simpler way by means of bisigmoidal equations. Such equations could be successfully used in a microbiology and toxicology context to discriminate between hormesis and other biphasic phenomena.
Murado
Miguel A
MA
Grupo de Reciclado y Valorización de Materiales Residuales (REVAL), Instituto de Investigacións Mariñas (CSIC), R/Eduardo Cabello, 6 Vigo-36208-Galicia, Spain. recicla@iim.csic.es
Vázquez
José A
JA
D000890:Anti-Infective Agents / Q000494:pharmacology*; D056573:Carnobacterium / Q000187:drug effects* / Q000254:growth & development*; D004305:Dose-Response Relationship, Drug; D007934:Leuconostoc / Q000187:drug effects* / Q000254:growth & development*; D008954:Models, Biological; D008962:Models, Theoretical; D009561:Nisin / Q000494:pharmacology; D019800:Phenol / Q000494:pharmacology; D013997:Time Factors
D000890:Anti-Infective Agents; D009561:Nisin; D019800:Phenol