Zinc Blockade of SOS Response Inhibits Horizontal Transfer of Antibiotic Resistance Genes in Enteric Bacteria

• Published in: Frontiers in cellular and infection microbiology Vol. 8; p. 410
• Main Authors: Crane, John K, Cheema, Muhammad B, Olyer, Michael A, Sutton, Mark D
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.11.2018
• Subjects: antibiotic resistance; Cellular and Infection Microbiology; CTX-M27; electrophoretic mobility shift assay; Enterobacter cloacae; extended spectrum beta lactamase; RecA; Zinc pyrithione; electrophoretic mobility shift assay; Enterobacter cloacae; antibiotic resistance; RecA; CTX-M27; extended spectrum beta lactamase
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2018.00410

The SOS response is a conserved response to DNA damage that is found in Gram-negative and Gram-positive bacteria. When DNA damage is sustained and severe, activation of error-prone DNA polymerases can induce a higher mutation rate than is normally observed, which is called the SOS mutator phenotype or hypermutation. We previously showed that zinc blocked the hypermutation response induced by quinolone antibiotics and mitomycin C in and . In this study, we demonstrate that zinc blocks the SOS-induced development of chloramphenicol resistance in . Zinc also blocked the transfer of an extended spectrum beta-lactamase (ESBL) gene from to a susceptible strain. A zinc ionophore, zinc pyrithione, was ~100-fold more potent than zinc salts in inhibition of ciprofloxacin-induced hypermutation in . Other divalent metals, such as iron and manganese, failed to inhibit these responses. Electrophoretic mobility shift assays (EMSAs) revealed that zinc, but not iron or manganese, blocked the ability of the RecA protein to bind to single-stranded DNA, an important early step in the recognition of DNA damage in enteric bacteria. This suggests a mechanism for zinc's inhibitory effects on bacterial SOS responses, including hypermutation.