Cooper Kerry K, Mourkas Evangelos, Schiaffino Francesca, Parker Craig T, Pinedo Vasquez Tackeshy N, Garcia Bardales Paul F, Peñataro Yori Pablo, Paredes Olortegui Maribel, Manzanares Villanueva Katia, Romaina Cachique Lucero, Silva Delgado Hermann, Hitchings Matthew D, Huynh Steven, Sheppard Samuel K, Pascoe Ben, Kosek Margaret N
School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA.
Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
mBio. 2025 Feb 5;16(2):e0205424. doi: 10.1128/mbio.02054-24. Epub 2024 Dec 27.
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 is 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 , which encodes an efflux pump conferring high levels of combined resistance to fluoroquinolones and macrolides in strains isolated from poultry ( = 75) and children ( = 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 operon and identified a potential genetic bottleneck for the and genes. While most alleles segregate by species, alleles associated with high resistance to fluoroquinolones and macrolides were found in both and . We inferred that the likely ancestry of these alleles was from and was later acquired by through recombination. Publicly accessible global genomic data from 16,120 genomes identified these mutations in approximately 6% of and isolates globally, with higher prevalence in samples from poultry in many countries, including Peru. Our findings suggest that these extensively drug-resistant strains originated from in poultry.IMPORTANCEAntimicrobial resistance in is a growing public health concern, driven by the rapid evolution and zoonotic transmission of resistant strains. This study focuses on mutations in the cmeABC efflux pump, which confer high resistance to fluoroquinolones and macrolides, the two most effective oral antibiotics for human campylobacteriosis. By analyzing genomes from poultry and children in Iquitos, Peru, as well as global genomic data sets, we identified a significant prevalence of these resistance-associated mutations, particularly in poultry and children. Our findings suggest that these mutations originated in and spread to through recombination. Globally, these mutations are found in approximately 6% of isolates, with higher prevalence in poultry in multiple countries. This research underscores the critical role of genomic epidemiology in understanding the origins, evolution, and dissemination of antimicrobial resistance and highlights the need to address poultry as a reservoir for resistant .
由于抗菌药物耐药性的快速进展演变以及人畜共患病源和人类源的有效传播，这是一个严重的健康威胁。对氟喹诺酮类和大环内酯类药物的耐药性尤其令人担忧，因为这会影响目前可用于人类弯曲杆菌病的两种最有效的口服抗生素药物。在此，我们报告了操纵子的流行情况及其在全球的分布，该操纵子编码一种外排泵，赋予从家禽（n = 75）和儿童（n = 177）分离出的弯曲杆菌菌株对氟喹诺酮类和大环内酯类药物高水平的联合耐药性。这些突变在秘鲁伊基托斯的家禽分离株（62.7%）和儿童分离株（29.4%）中被发现高度流行。我们研究了cmeABC操纵子中基因的群体结构，并确定了cmeA和cmeB基因的一个潜在遗传瓶颈。虽然大多数cmeA等位基因按物种分离，但在空肠弯曲杆菌和结肠弯曲杆菌中都发现了与对氟喹诺酮类和大环内酯类药物高耐药性相关的等位基因。我们推断这些等位基因可能起源于空肠弯曲杆菌，后来通过重组被结肠弯曲杆菌获得。来自16120株弯曲杆菌基因组的公开全球基因组数据在全球约6%的空肠弯曲杆菌和结肠弯曲杆菌分离株中鉴定出了这些突变，在包括秘鲁在内的许多国家的家禽样本中患病率更高。我们的研究结果表明，这些广泛耐药的结肠弯曲杆菌菌株起源于家禽中的空肠弯曲杆菌。
重要性
弯曲杆菌中的抗菌药物耐药性是一个日益严重的公共卫生问题，由耐药菌株的快速演变和人畜共患病传播所驱动。本研究聚焦于cmeABC外排泵中的突变，这些突变赋予对氟喹诺酮类和大环内酯类药物高耐药性，这两种药物是治疗人类弯曲杆菌病最有效的口服抗生素。通过分析秘鲁伊基托斯的家禽和儿童的基因组以及全球基因组数据集，我们发现这些与耐药性相关的突变显著流行，尤其是在家禽和儿童中。我们的研究结果表明，这些突变起源于空肠弯曲杆菌并通过重组传播到结肠弯曲杆菌。在全球范围内，这些突变在约6%的分离株中被发现，在多个国家的家禽中患病率更高。这项研究强调了基因组流行病学在理解抗菌药物耐药性的起源、演变和传播中的关键作用，并突出了将家禽作为耐药结肠弯曲杆菌储存库加以应对的必要性。
