Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome

Abstract

Antibiotic resistance is a global challenge that impacts all pharmaceutically used antibiotics. The origin of the genes associated with this resistance is of significant importance to our understanding of the evolution and dissemination of antibiotic resistance in pathogens. A growing body of evidence implicates environmental organisms as reservoirs of these resistance genes; however, the role of anthropogenic use of antibiotics in the emergence of these genes is controversial. We report a screen of a sample of the culturable microbiome of Lechuguilla Cave, New Mexico, in a region of the cave that has been isolated for over 4 million years. We report that, like surface microbes, these bacteria were highly resistant to antibiotics; some strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics including daptomycin, an antibiotic of last resort in the treatment of drug resistant Gram-positive pathogens. Enzyme-mediated mechanisms of resistance were also discovered for natural and semi-synthetic macrolide antibiotics via glycosylation and through a kinase-mediated phosphorylation mechanism. Sequencing of the genome of one of the resistant bacteria identified a macrolide kinase encoding gene and characterization of its product revealed it to be related to a known family of kinases circulating in modern drug resistant pathogens. The implications of this study are significant to our understanding of the prevalence of resistance, even in microbiomes isolated from human use of antibiotics. This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome.

Potential Impact of Environmental Bacteriophages in Spreading Antibiotic Resistance Genes

“…But, at the same time, a growing body of evidence points to the potentially important role of environmental microorganisms from ecosystems in which the presence of antibiotics produced by humans is expected to be very low or completely absent. Such ecosystems are as varied as soil [2], a microcave isolated for over four million years [3], and pristine waters [4].…”

Antimicrobial drug resistance affects broad changes in metabolomic phenotype in addition to secondary metabolism

“…natural products | metabolite discovery | multivariate statistical analysis I ncreasing evidence is accumulating that a large fraction of antibiotic resistance may be elicited via horizontal transfer of resistance elements from the reservoir of microbial diversity found in soil (1,2). Additionally, bacterial resistance toward a significant subset of antibiotics is rapidly generated vertically by mutations in central housekeeping genes encoding polymerases and ribosomal subunits.…”

Emergence of new infections in the 21st century and identification of pathogens using next generation sequencing

“…Moreover, the VanA protein, one the most important products of glycopeptide resistance genes, has preserved its function and 3D structure over centuries [99]. In another study, bacteria found in caves that had had no contact with the surface for over 4 million years proved to be resistant to 14 different antibiotics [100]. Genotyping and biochemical assays show that resistance genes are present in the microbial pangenome regardless of the human-induced selective pressure [100].…”

“…In another study, bacteria found in caves that had had no contact with the surface for over 4 million years proved to be resistant to 14 different antibiotics [100]. Genotyping and biochemical assays show that resistance genes are present in the microbial pangenome regardless of the human-induced selective pressure [100].…”