The Resistome: A Comprehensive Database of Escherichia coli Resistance Phenotypes

Abstract

The microbial ability to resist stressful environmental conditions and chemical inhibitors is of great industrial and medical interest. Much of the data related to mutation-based stress resistance, however, is scattered through the academic literature, making it difficult to apply systematic analyses to this wealth of information. To address this issue, we introduce the Resistome database: a literature-curated collection of Escherichia coli genotypes-phenotypes containing over 5,000 mutants that resist hundreds of compounds and environmental conditions. We use the Resistome to understand our current state of knowledge regarding resistance and to detect potential synergy or antagonism between resistance phenotypes. Our data set represents one of the most comprehensive collections of genomic data related to resistance currently available. Future development will focus on the construction of a combined genomic-transcriptomic-proteomic framework for understanding E. coli's resistance biology. The Resistome can be downloaded at https://bitbucket.org/jdwinkler/resistome_release/overview .

Insights on Osmotic Tolerance Mechanisms in Escherichia coli Gained from an rpoC Mutation

“…Prior work has shown that moderate concentration of NaCl can protect E. coli from acetic acid toxicity [ 48 ]; here we show that the cross tolerance is reciprocal, that moderate concentrations of acetic acid can also protect E. coli from NaCl stress. Interestingly, a statistically significant overlap ( p < 10 −20 , Fisher’s exact test) between metabolites level changes in organic acid and osmotolerant E. coli mutants has been detected using an updated version of the Resistome combined with a recent genome-wide survey of genotype–metabolite relationships [ 49 , 50 ], providing additional evidence that the improved osmotic tolerance of EJW3 may also result from the higher production of acetic acid.…”

Refactoring the Genetic Code for Increased Evolvability

“…This plot highlights the notion that many SNR-accessible amino acids are chemically similar as depicted by the multitude of red edges. Edge distribution of all genetic codes presented in this study are shown in Fig S2. To investigate the potential effect of mutation buffering that favors SNR-induced amino acid replacements, we analyzed a recently published collection of 2679 amino acid changes generated by various random methods associated with diverse resistance phenotypes (43). The results show that almost all mutations found could be explained by a single nucleotide replacement, with double-and triple nucleotide replacements being required for at most 3.5% of all detected mutations (Fig.…”

Antimicrobial Resistance in the Environment

“…While a handful of databases are available for ARGs, data related to antibiotic resistance based on mutations is more scattered. Thus, a recently described study assembled the Resistome database, which consists of a collection of over 5,000 mutants in E. coli that resist over 200 compounds and environmental conditions (Winkler et al, 2016). One study also described the development of a database to map antibiotic resistance observed in environmental and clinical samples .…”