The repertoire of ABC proteins in Clostridioides difficile

Methinee Pipatthana; Phurt Harnvoravongchai; Pisut Pongchaikul; Somsak Likhitrattanapisal; Matthew Phanchana; Surang Chankhamhaengdecha; Tavan Janvilisri

doi:10.1016/j.csbj.2021.05.012

The repertoire of ABC proteins in Clostridioides difficile

Comput Struct Biotechnol J. 2021 May 8:19:2905-2920. doi: 10.1016/j.csbj.2021.05.012. eCollection 2021.

Authors

Methinee Pipatthana¹, Phurt Harnvoravongchai², Pisut Pongchaikul³, Somsak Likhitrattanapisal⁴, Matthew Phanchana⁵, Surang Chankhamhaengdecha², Tavan Janvilisri¹

Affiliations

¹ Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
² Department of Biology, Faculty of Science, Mahidol University, Bangkok, Thailand.
³ Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakarn, Thailand.
⁴ Thailand Bioresource Research Center (TBRC), National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.
⁵ Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Abstract

ATP-binding cassette (ABC) transporters belong to one of the largest membrane protein superfamilies, which function in translocating substrates across biological membranes using energy from ATP hydrolysis. Currently, the classification of ABC transporters in Clostridioides difficile is not complete. Therefore, the sequence-function relationship of all ABC proteins encoded within the C. difficile genome was analyzed. Identification of protein domains associated with the ABC system in the C. difficile 630 reference genome revealed 226 domains: 97 nucleotide-binding domains (NBDs), 98 transmembrane domains (TMDs), 30 substrate-binding domains (SBDs), and one domain with features of an adaptor protein. Gene organization and transcriptional unit analyses indicated the presence of 78 ABC systems comprising 28 importers and 50 exporters. Based on NBD sequence similarity, ABC transporters were classified into 12 sub-families according to their substrates. Interestingly, all ABC exporters, accounting for 64% of the total ABC systems, are involved in antibiotic resistance. Based on analysis of ABC proteins from 49 C. difficile strains, the majority of core NBDs are predicted to be involved in multidrug resistance systems, consistent with the ability of this organism to survive exposure to an array of antibiotics. Our findings herein provide another step toward a better understanding of the function and evolutionary relationships of ABC proteins in this pathogen.

Keywords: ABC classification; ABC transporter/protein, ATP-binding cassette transporter/protein; ATP-binding cassette transporter; Active transporter; Antimicrobial resistance; ECF-type transporter, Energy coupling factor-type transporter; In silico analysis; NBD, Nucleotide-binding domain; NP, Nucleotide-binding domain (NBD)-containing protein; SBD, Substrate-binding domain; SP, Substrate-binding domain (SBD)-containing protein; TMD, Transmembrane domain; TP, Transmembrane protein.