and adaptive forms of resistant gene expression occur under different environmental pressures and lead to significant challenges in developing effective treatments in response. Our understanding of how humans create additional positive selective pressure for antibiotic resistance in non-clinical environments is essential now more than ever. The rise in antibiotic resistance has severely reduced the efficacy of antibiotic drugs, posing severe cause for concern in the realm of drug development and maintaining public health. Human-manufactured antibiotics are not the only source of antibiotic resistant pressure in the wild, as antibiotics are present at various concentrations and function as both defense and signaling mechanisms, selecting for antibiotic resistance naturally in the environment. For this reason, studying natural antibiotics and the patterns of antibiotic resistance that naturally arise in the wild may help us to predict and respond to antibiotic resistance in clinical settings. Analyses of metagenomic sequence data are useful tools for understanding how human impact influences the spread of resistance genes. An effect of the introduction of high levels of human-made antibiotics in the environment is the promotion of antibiotic resistance even in the absence of natural antibiotic production. Secondary stress conditions like heavy metal pollution cause higher HGT as a stress response, which also likely contributes to the dissemination of antibiotic resistant genes. Also, rapid increase in human populations without adequate wastewater treatment allows for more chance for human pathogens to be in contact with environmental resistance-carrying bacteria, so it's important to look to wastewater treatment as a source of HGT. Infection resistance The resistome also refers to an inherited set of genes used to resist infections. This concept is also referred to as innate immunity, and resistance genes within the resistome provide different functions for immune response, and are differentially transcribed. Interestingly, in one study of Arabidopsis thaliana, activated regions on the chromosome for resistance against both bacteria and viruses are clustered together, likely meaning they are co-regulated. Comparing different mutations in the germline can be used to help define the size and position of the resistome, this set of genes conferring an inherited immune response. Because of mutation, the ‘universal resistome’, a set of resistance genes shared among all mice, similar to the concept of the pan-microbiome, is likely extremely small. References Antimicrobial resistance Genomics