557. Impact of Heavy Metal Exposure in the Transcriptional Response of Methicillin--Resistant Staphylococcus aureus (MRSA)-USA300 Latin-American Variant (USA300-LV)

BACKGROUND: USA 300-LV is the predominant MRSA clone in Colombia and contains a genomic island designated “COMER” with genes for copper (Cu) and mercury (Hg) resistance. HM environmental contamination is a serious threat to public health in Colombia and could also influence the selection and evolution of HM resistance genes in MRSA. Here, we investigate the global transcriptomic responses of USA300-LV after exposure to HM under the hypothesis that USA300-LV strains are highly capable of sustaining higher HM concentrations METHODS: We performed comparative RNAseq experiments in USA300-LV clinical strain (CA-MRSA12). Total RNA was isolated in exponential phase in the absence and presence of sub-inhibitory concentrations of Cu and Hg (3 replicates). cDNA libraries were prepared and sequenced on an Illumina platform. Differentially expressed genes (DEG) were calculated by DeSeq2 (p-adjusted value ˂ 0.01) and results on 19 selected genes were confirmed by qRT-PCR. RESULTS: US300-LV exhibited a larger number of differentially expressed genes when exposed to Hg (n = 114) compared with Cu treatment (n = 16). The most common functional groups of genes upregulated after Hg exposure included those involved in amino acid metabolism (n = 18). In contrast, 45 genes were downregulated after Hg exposure, mostly associated to host immune system defense (n = 11). qRT-PCR confirmed that the most upregulated genes were those involved in murein hydrolase activity, Hg resistance and the transcriptional regulator Cro/CI. Of 9 genes that were downregulated, functional groups included ype VII secretion system, immune modulators and leucocidins. Copper treatment resulted in only 12 genes that were upregulated including those in the COMER element (n = 6), aminoacid metabolism (n = 3), ROS response (n = 1), host immune system defense (n = 1) and unknown function (n = 1). Downregulated genes were those associated to host immune system defense (n = 2), energy generation (n = 1) and unknown function (n = 1). CONCLUSION: Differential adaptive responses after exposure to HM in USA300-LV suggest a role in the evolution of antimicrobial resistance and successful spread in the region. Metabolic adaptations involving amino acid metabolism seem to play a role in the evolution of HM resistance in MRSA. DISCLOSURES: All authors: No reported disclosures.