Emergence of antibiotic-resistant pathogens in ancient deep-sea sediments predates anthropogenic antibiotic use

The rapid escalation of antibiotic resistance of pathogenic bacteria has become a critical global public health threat. Despite the extensive use of antibiotics in medicine, debates on the origins of antibiotic-resistance pathogenic bacterium remain unresolved. In this study, five antibiotic-resistant pathogenic bacteria (S. epidermidis, S. warneri, A. viridans, B. cereus or S. haemolyticus), which could destroy the mouse intestines, were isolated from the deep-sea sediments with the geological ages of 8,008-23,931 years, indicating that the emergence of antibiotic-resistant pathogens predated the anthropogenic antibiotic use. The deep-sea pathogenic bacteria carried multiple antibiotic-resistant genes in their genomes, which exhibited the antibiotic resistance comparable to those of the current antibiotic-resistant pathogens. During the long history of coexistence with the antibiotic-producing bacterium in the deep sea, the deep-sea pathogenic bacteria evolved the resistance to antibiotics. The antibiotic-resistant pathogenic bacteria were distributed in the deep sea, the extreme ecosystem largely unaffected by human activities. In this context, our findings contributed novel insights into the natural origin and evolution of antibiotic-resistant pathogenic bacteria, providing a foundation for developing sustainable strategies to mitigate the global health challenge of antibiotic resistance.