Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome

By Kirandeep Bhullar, Nicholas Waglechner, Andrew C. Pawlowski, K. Koteva, Eric D. Banks, M. Johnston, Hazel A. Barton, Gerard D. Wright. PLoS ONE, 2012

703 citations recorded by the source corpus.

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.

Subfields: Ecology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/92ed86438f56f49216e9d104f1b2ff2028930214

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Ecology

1. Y. Taur
2. Eric G. Pamer

In Molecular Biology

1. Y. Taur
2. Eric G. Pamer
3. E. Peterson
4. P. Kaur

Citations in the corpus

• Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy (2019, background): “For example, 65% of gram-negative and 70% of gram-positive bacterial isolates from a pristine cave microbiome carried multiple functional antibiotic resistance genes, indicating that multiple resistance is the environmental norm, rather than an exceptional response to high anthropogenic antibiotic p”
• Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens (2018, background): “Finally, there is also strong evidence showing that the antibiotic resistance gene sequences are ancient and predate the use of antibiotics (D’Costa et al., 2011; Bhullar et al., 2012; Warinner et al., 2014; Perron et al., 2015; Kashuba et al., 2017).”
• Co-selection of antibiotic and heavy metal resistance in freshwater bacteria (2016, background): “Moreover many reports hint to a non-negligible amount of ARGs even in areas that are not directly impacted, such as permafrost and caves (D’Costa et al., 2011; Bhullar et al., 2012; Segawa et al., 2013).”
• Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “Accordingly, ARGs were identified in microbiota from an 11th century AD mummy [94], in a 30 000 year-old permafrost sediment [95], as well as in a cave in New Mexico that had been isolated for millions of years [96]; none of these environments could have been influenced by the presence of modern-day”
• ARG-ANNOT, a New Bioinformatic Tool To Discover Antibiotic Resistance Genes in Bacterial Genomes (2013, background): “Recent evidence from environmental, human, and animal microbial metagenomic studies showed that AR has an ancient origin and evolution and that the pool of AR genes (the resistome) remaining to be discovered in these reservoirs is immense (5, 6).”