Potentiation of the Selective Effect of Antibiotics by Metal Ions

• Complex mixtures of antibiotics and metals are present in many environments ranging from municipal sewage to irrigation water and manure used as agricultural fertilizer. Such mixtures of drugs and metals exert unique selection pressures on local bacterial communities and could function as hotspots for enrichment of antibiotic resistance genes. The presence of metals in the environment has previously been linked to increases in tolerance to antibiotics. In this study, we investigated metal-potentiated selection of antibiotic resistant Salmonella enterica strains. Six environmentally relevant metals were examined in combinations with three different antibiotics. By performing competitions between an antibiotic resistant mutant and the isogenic wild type in each metal-antibiotic combination, we assessed the minimal selective concentration (MSC) of the antibiotic for the resistant strain. The metals silver, cadmium and mercury all exhibited potentiating effects, reducing the MSC of the antibiotic up to 5-fold as compared to in the absence of the metal. We further show that the potentiating metals increased permeability of the cellular outer membrane. These results demonstrate that the presence of a metal can decrease the concentration of an antibiotic required to select for an antibiotic resistant strain, and they indicate that this process involves metal-facilitated uptake of the antibiotic following damage to the outer membrane.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Annan medicin och hälsovetenskap -- Övrig annan medicin och hälsovetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Other Medical and Health Sciences -- Other Medical and Health Sciences not elsewhere specified (hsv//eng)

Nyckelord

Antibiotic resistance

Selection

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)