Genetic Characteristics of Novel IncpSE5381-aadB Plasmids, Integrative and Mobilizable Elements, and Integrative and Conjugative Elements in Pseudomonas aeruginosa

Jiaqi He,1,* Xiuhui Lu,2,* Chenchen Yuan,1 Yali Zheng,2 Fangzhou Chen,2 Jing Luo,2 Kejiao Ma,2 Fan Yang,2 Peng Wang,2 Dongsheng Zhou,2 Li Wang,1 Zhe Yin2 1Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China, Email wangli851217@163.com Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.Methods: Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.Results: The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn 7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn 7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn 6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn 501-related unit transposons, two Tn 1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.Conclusion: The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.Keywords: Pseudomonas aeruginosa, genome sequencing, mobile genetic elements, antimicrobial resistance, OXA