Janse Ingmar, Beeloo Rick, Swart Arno, Visser Michael, Schouls Leo, van Duijkeren Engeline, van Passel Mark W J
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Utrecht, The Netherlands.
Sequencing and Bioinformatics, Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, The Netherlands.
PeerJ. 2021 Mar 9;9:e11000. doi: 10.7717/peerj.11000. eCollection 2021.
Genome sequences provide information on the genetic elements present in an organism, and currently there are databases containing hundreds of thousands of bacterial genome sequences. These repositories allow for mining patterns concerning antibiotic resistance gene occurrence in both pathogenic and non-pathogenic bacteria in e.g. natural or animal environments, and link these to relevant metadata such as bacterial host species, country and year of isolation, and co-occurrence with other resistance genes. In addition, the advances in the prediction of mobile genetic elements, and discerning chromosomal from plasmid DNA, broadens our view on the mechanism mediating dissemination. In this study we utilize the vast amount of data in the public database PATRIC to investigate the dissemination of carbapenemase-encoding genes (CEGs), the emergence and spread of which is considered a grave public health concern. Based on publicly available genome sequences from PATRIC and manually curated CEG sequences from the beta lactam database, we found 7,964 bacterial genomes, belonging to at least 70 distinct species, that carry in total 9,892 CEGs, amongst which , , , and . We were able to distinguish between chromosomally located resistance genes (4,137; 42%) and plasmid-located resistance genes (5,753; 58%). We found that a large proportion of the identified CEGs were identical, i.e. displayed 100% nucleotide similarity in multiple bacterial species (8,361 out of 9,892 genes; 85%). For example, the New Delhi metallo-beta-lactamase NDM-1 was found in 42 distinct bacterial species, and present in seven different environments. Our data show the extent of carbapenem-resistance far beyond the canonical species or . These types of data complement previous systematic reviews, in which carbapenem-resistant Enterobacteriaceae were found in wildlife, livestock and companion animals. Considering the widespread distribution of CEGs, we see a need for comprehensive surveillance and transmission studies covering more host species and environments, akin to previous extensive surveys that focused on extended spectrum beta-lactamases. This may help to fully appreciate the spread of CEGs and improve the understanding of mechanisms underlying transmission, which could lead to interventions minimizing transmission to humans.
基因组序列提供了关于生物体中存在的遗传元件的信息，目前有包含数十万细菌基因组序列的数据库。这些储存库有助于挖掘有关例如自然或动物环境中致病和非致病细菌中抗生素抗性基因出现情况的模式，并将这些与相关元数据联系起来，如细菌宿主物种、分离的国家和年份，以及与其他抗性基因的共现情况。此外，在移动遗传元件预测以及区分染色体DNA和质粒DNA方面的进展，拓宽了我们对介导传播机制的认识。在本研究中，我们利用公共数据库PATRIC中的大量数据来研究碳青霉烯酶编码基因（CEGs）的传播，其出现和传播被认为是一个严重的公共卫生问题。基于来自PATRIC的公开可用基因组序列以及来自β-内酰胺数据库的人工整理的CEG序列，我们发现了7964个细菌基因组，属于至少70个不同的物种，总共携带9892个CEGs，其中 、 、 以及 。我们能够区分位于染色体上的抗性基因（4137个；42%）和位于质粒上的抗性基因（5753个；58%）。我们发现，很大一部分已鉴定的CEGs是相同的，即在多个细菌物种中显示出100%的核苷酸相似性（9892个基因中的8361个；85%）。例如，新德里金属β-内酰胺酶NDM-1在42个不同的细菌物种中被发现，并存在于七种不同的环境中。我们的数据显示碳青霉烯抗性的范围远远超出了典型物种 或 。这些类型的数据补充了以前的系统综述，其中在野生动物、家畜和伴侣动物中发现了耐碳青霉烯肠杆菌科细菌。考虑到CEGs的广泛分布，我们认为需要进行全面的监测和传播研究，涵盖更多的宿主物种和环境，类似于以前专注于超广谱β-内酰胺酶的广泛调查。这可能有助于充分了解CEGs的传播，并增进对传播潜在机制的理解，从而可能导致采取干预措施尽量减少向人类的传播。
