High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction

The selective perturbation of complex
microbial ecosystems to predictably
influence outcomes in engineered and industrial environments remains
a grand challenge for geomicrobiology. In some industrial ecosystems,
such as oil reservoirs, sulfate reducing microorganisms (SRM) produce
hydrogen sulfide which is toxic, explosive, and corrosive. Despite
the economic cost of sulfidogenesis, there has been minimal exploration
of the chemical space of possible inhibitory compounds, and very little
work has quantitatively assessed the selectivity of putative souring
treatments. We have developed a high-throughput screening strategy
to identify potent and selective inhibitors of SRM, quantitatively
ranked the selectivity and potency of hundreds of compounds and identified
previously unrecognized SRM selective inhibitors and synergistic interactions
between inhibitors. Zinc pyrithione is the most potent inhibitor of
sulfidogenesis that we identified, and is several orders of magnitude
more potent than commonly used industrial biocides. Both zinc and
copper pyrithione are also moderately selective against SRM. The high-throughput
(HT) approach we present can be readily adapted to target SRM in diverse
environments and similar strategies could be used to quantify the
potency and selectivity of inhibitors of a variety of microbial metabolisms.
Our findings and approach are relevant to efforts to engineer environmental
ecosystems and also to understand the role of natural gradients in
shaping microbial niche space.