Emergence of methicillin resistance predates the clinical use of antibiotics

Abstract

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

Genomic Analysis of ESBL-Producing E. coli in Wildlife from North-Eastern Germany

“…A recently published study draws a similar conclusion. The authors postulate that wildlife represents a previously unrecognized medium through which environmental ARMGs can be transferred to human clinical pathogens [ 40 ].…”

Phages against Pathogenic Bacterial Biofilms and Biofilm-Based Infections: A Review

“…The morphology and physiological functions of bacteria in biofilms are entirely different from those of planktonic bacteria free in suspension, allowing bacteria within biofilms to be upwards of 1000-fold more resistant to conventional antibiotic treatments and host immune responses as compared to the planktonic cells [4,5]. With the co-evolutionary adaptation of notorious human pathogens to hosts and the abuse of antibiotics in modern clinical medicine, intrinsic bacterial resistance to antibiotics has globally risen to a high-risk level [6]. Hence, efficient alternative therapeutic strategies are urgently needed to prevent pathogenic bacterial biofilm formation and control biofilm-based infections.…”

Impact of the Stringent Stress Response on the Expression of Methicillin Resistance in Staphylococcaceae Strains Carrying mecA, mecA1 and mecC

“…Interestingly, although antibiotic resistance is believed to arise primarily from human antibiotic overuse [ 15 ], a recent study [ 16 ] making use of time-resolved phylogenies suggested that particular lineages of mecC -MRSA appeared in European hedgehogs 200 years ago, i.e., more than a century before the first description of MRSA in humans. These lineages emerged in hedgehogs colonized with S. aureus and co-infected with a β-lactam-producer dermatophyte, Trichophyton erinacei .…”

“…These lineages emerged in hedgehogs colonized with S. aureus and co-infected with a β-lactam-producer dermatophyte, Trichophyton erinacei . The mecC -MRSA lineages developed to resist the penicillin produced by T. erinaceid and eventually spread within local hedgehog populations and between hedgehogs and secondary hosts, such as livestock and humans [ 16 ].…”