Sharing of cmeRABC alleles between C. coli and C. jejuni associated with extensive drug resistance in Campylobacter isolates from infants and poultry in the Peruvian Amazon

Authors: COOPER, KERRY - University Of Arizona; MOURKAS, EVANGELOS - University Of Oxford; SCHIAFFINO, FRANCESCA - Universidad Peruana Cayetano Heredia (UPCH); Parker, Craig; PINEDO-VASQUEZ, TACKESHY - Prisma Charitable Association; GARCIA-BARDALES, PAUL - Prisma Charitable Association; PENATARO-YORI, PABLO - University Of Virginia; PAREDES-OLORTEGUI, MARIBEL - Prisma Charitable Association; VILLANUEVA-MANZANARE, KATIA - Prisma Charitable Association; ROMAINA-CACHIQUE, LUCERO - Prisma Charitable Association; SILVA-DELGADO, HERMANN - National University Of The Peruvian Amazon; HITCHINGS, MATTHEW - Swansea University; Huynh, Steven; SHEPPARD, SAMUEL - University Of Oxford; PASCOE, BEN - University Of Oxford; KOSEK, MARGARET - University Of Virginia

Submitted to: mBio
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2024
Publication Date: 12/27/2024
Citation: Cooper, K.K., Mourkas, E., Schiaffino, F., Parker, C.T., Pinedo-Vasquez, T., Garcia-Bardales, P.F., Penataro-Yori, P., Paredes-Olortegui, M., Villanueva-Manzanare, K., Romaina-Cachique, L., Silva-Delgado, H., Hitchings, M.D., Huynh, S., Sheppard, S.K., Pascoe, B., Kosek, M.N. 2024. Sharing of cmeRABC alleles between C. coli and C. jejuni associated with extensive drug resistance in Campylobacter isolates from infants and poultry in the Peruvian Amazon. mBio. 16(2). Article e02054-24. https://doi.org/10.1128/mbio.02054-24.
DOI: https://doi.org/10.1128/mbio.02054-24

Interpretive Summary: Campylobacter is the leading cause of bacterial gastroenteritis worldwide. Rising global trends in multidrug resistant C. jejuni and C. coli represent a serious public health risk. Fluoroquinolone-resistant strains are identified as a serious threat by both the United States Centers for Disease Control (CDC) and the World Health Organization (WHO). Consequently, azithromycin (a macrolide) has become the primary treatment for acute gastroenteritis caused by Campylobacter. This study highlights the rise of combined fluoroquinolone and macrolide-resistant Campylobacter spp., which pose a significant public health threat in low- and middle-income countries (LMICs). Combined resistance to these antibiotics compromises the two most effective oral antibiotic agents currently available. The CmeABC efflux system enhances resistance to bile salts and synergizes with other resistance determinants, contributing to increased resistance to various antimicrobials. We identified a high prevalence of cmeB gene mutations in Campylobacter strains from both commercial poultry (61.8%) and infants (30.1%) in Iquitos, Peru, which confer resistance to the most effective oral antibiotics. Genetic analysis indicates that these high-resistance alleles likely originated in C. jejuni and were transferred to C. coli via recombination and global data comparisons show these mutations in about 6% of C. jejuni and C. coli isolates worldwide. This underscores the urgent need for genomic epidemiology to track the evolution and dissemination of antimicrobial resistance, informing better management strategies in both human and veterinary medicine, especially in LMICs where the public health impact is most severe.

Technical Abstract: Campylobacter is a serious health threat because of the rapid progressive evolution of antimicrobial resistance and efficient transmission from zoonotic as well as human sources. Resistance to fluoroquinolones and macrolides are particularly concerning as this compromises the two most effective oral antibiotic agents currently available for human Campylobacteriosis. Here, we report on the prevalence and worldwide distribution of the operon cmeRABC which encodes an efflux pump conferring high combined levels of fluoroquinolone and macrolide resistance in Campylobacter strains isolated from poultry (N= 75) and children (N= 177). These mutations were found to be highly prevalent in isolates from poultry (62.7%) and children (29.4%) in Iquitos, Peru. We investigated the population structure of genes in the cmeRABC operon and identified a potential genetic bottleneck for the cmeA and cmeB genes. While most cmeB alleles segregate by species, alleles associated with high resistance to fluoroquinolones and macrolides were found in both C. jejuni and C. coli. We inferred the likely ancestry of these alleles to be from C. jejuni that were later acquired by C. coli through recombination. Publicly accessible global genomic data from 16,120 Campylobacter genomes identified these mutations in approximately 6% of C. jejuni and C. coli isolates globally, with higher prevalence in samples from poultry in many countries, including Peru. Our findings suggest that these extensively drug resistant Campylobacter strains originate from C. jejuni in poultry.