Comparative Genomics Identified PenR E151V Substitution Associated with Carbapenem-Resistance Burkholderia cepacia Complex and a Novel Burkholderia cepacia Complex Specific OXA-1043 Subgroup

Ya-Chun Liao,1 Yao-Ting Huang,2,* Chien-Hao Tseng,1 Chia-Wei Liu,1 Po-Yu Liu1,3,4,* 1Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Computer Science and Information Engineering, National Chung Cheng University, Chiayi, Taiwan; 3Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung, Taiwan; 4Genome Center for Infectious Diseases, Taichung Veterans General Hospital, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Po-Yu Liu, Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Xitun District, Taichung, Taiwan, Tel +886-4-2359-2525, Fax +886-4-2359-5046, Email pyliu@vghtc.gov.twPurpose: Burkholderia cepacia complex (Bcc) is a known significant opportunistic pathogen causing morbidity and mortality, particularly in those with cystic fibrosis, chronic granulomatous disease, or immunocompromising host. Mortality of Bcc bloodstream infections among non-cystic fibrosis patients remained high. The antibiotic treatment for Bcc infection is quite challenging due to its intrinsic resistance to most antibiotics, and the resistance to carbapenems was the biggest concern among them. We aimed to realize the mechanism of carbapenem resistance in Bcc.Patients and Methods: Ten strains of Bcc were identified by the MALDI-TOF MS, and the drug susceptibility test was using VITEK 2 system. The Burkholderia cepacia complex genomes were sequenced via Nanopore GridIon. We also downloaded another ninety-five strains of Bcc from the National Center for Biotechnology Information database to evaluate the divergence between carbapenem-resistance and carbapenem-sensitive strains.Results: The genetic organization between carbapenem-sensitive and carbapenem-resistant strains of Bcc showed no difference. However, in the carbapenem-sensitive strain, E151V substitution in PenR was detected. In addition, a novel specific OXA family subgroup, blaOXA-1043 in Burkholderia cenocepacia was discovered.Conclusion: The E151V substitution in PenR may be associated with carbapenem-sensitive in Bcc. Moreover, the V151E mutation in PenR may be related to the activation of PenB, leading to Bcc resistance to carbapenems. Besides, a novel OXA family subgroup, blaOXA-1043, was found in Burkholderia cenocepacia, which differs from the previous OXA family.Keywords: Burkholderia cepacia complex, Burkholderia cenocepacia, carbapenem-resistant, whole-genome sequencing