UC Irvine

It is important to understand the evolution and prevalence of antibiotic resistance as it is considered a major threat to global public health. Predicting where new antibiotic resistance (AR) genes will rise is a challenge and especially important when new antibiotics are developed. Adaptive resistance allows sensitive bacterial cells to become transiently resistant to antibiotics through changes in gene expression. This provides an opportune time for cells to develop more efficient resistance mechanisms and permanent resistance to higher antibiotic concentrations. Intraspecific genomic diversity may be a driving force in the emergence of adaptive antibiotic resistance. Here, I use an amplification assay adapted from functional metagenomics to investigate cryptic antibiotic resistance, an adaptive resistance mechanism, across eight micro-diverse Escherichia coli from clinical and laboratory origins. Cryptic (unclassified) AR genes primarily conferred resistance within clinical strains as opposed to known AR genes as hypothesized. Most genes conferring resistance within multiple strains were classified AR genes. Cryptic AR genes are highly variable as most conferred resistance in only one strain. Hydrophilic antibiotics are more likely to induce cryptic resistance as resistance occurred to all hydrophilic antibiotics tested. These studies may help detect novel AR genes that confer resistance when upregulated. Additionally, it is important to study antibiotic resistance in the environment, including coastal water. At the beach, people may ingest bacteria harboring AR genes which can lead to infection and/or transfer of genes to commensal and opportunistic pathogens resident in the human microbiome. The ingestion of seafood potentially harboring antibiotic resistant bacteria can lead to indirect contact with antibiotic resistance. Through a ten-year time series, I used metagenomics to provide a comprehensive understanding of the AR genes present within Newport Beach, CA seawater, the temporal distribution of these genes, and the factors driving their frequencies. I found that seasonal and interannual trends of AR genes vary by gene and the taxa carrying them as opposed to a general increase of most resistance genes during specific seasons. However, I found that precipitation and Enterococcus levels may be accurate indicators for total AR gene levels in Newport beach coastal water. Mostly marine taxa carry AR genes in Newport Beach coastal water, but there are also terrestrial taxa and opportunistic pathogens harboring AR genes. Non-marine taxa may be washed in with rain, people, or sewage spills. By using metagenomics, I was able to elucidate the AR gene reservoir in Newport Beach coastal water.