ATP-binding cassette (ABC) transporters: structures and roles in bacterial pathogenesis

Abstract

Adenosine triphosphate (ATP)-binding cassette (ABC) transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer, against the concentration gradient. These transporters comprise two highly conserved nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Unlike ABC exporters, prokaryotic ABC importers require an additional substrate-binding protein (SBP) as a recognition site for specific substrate translocation. The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections. The existing literature has highlighted the roles of ABC transporters in bacterial growth, pathogenesis, and virulence. These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances. This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.

Keywords: ATP-binding cassette (ABC) transporter; Bacterial pathogenesis; Virulence.

Fig. 1. An experimentally determined structure of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter (PDB ID: 5B58) derived from Naoe et al. (2016). (a) A substrate-binding protein (SBP) is situated at the periplasm, fused to the transmembrane domains (TMDs) at the surface of the inner membrane. Meanwhile, nucleotide-binding domains (NBDs), which facilitated the hydrolysis of ATP, are located in the cytoplasm. (b) The highly conserved motifs in an NBD dimer are colored: red, Walker A; orange, Walker B; yellow, LSGGQ; cyan, D-loop; purple, H-loop; pink, Q-loop. Figure created with BioRender.com.

Fig. 2. Roles of adenosine triphosphate (ATP)-binding cassette (ABC) importers and exporters in bacterial adherence. (a) ABC importers import metal ions that act as cofactors for various cellular process and protein structural stability, including the production of adhesins and pili involved in bacterial adherence (Izoré et al., 2010; Honsa et al., 2013). Some substrate-binding lipoproteins of ABC systems serve as adhesins for bacterial attachment to host cells, for example, Streptococcus pyogenes HtsABC (Song et al., 2018) and Streptococcus pneumoniae SPD_1609 (Yang et al., 2019). Certain dipeptide transporters are also involved in heme transport during iron starvation, thereby contributing to the structure of adherence proteins, for instance, DppABCD in Mycobacterium tuberculosis (Mitra et al., 2019) and DppBCDF in Haemophilus influenzae (Rodríguez-Arce et al., 2019). ABC importers of essential nutrients, such as amino acids and inorganic compounds, are also important for bacterial metabolism and the synthesis of biomolecules for bacterial survival during host invasion. In particular, ABC systems facilitate the transportation of sulfate/thiosulfate, molybdate, nitrate, lysine, and ornithine in Moraxella catarrhalis (Murphy et al., 2016). Oligopeptides imported by ABC systems function as signaling molecules that regulate the expression of genes participating in adherence, for example, OppABCDF of Vibrio alginolyticus (Liu et al., 2017). (b) ABC exporters that export substrates involved in the formation of the outer membrane. In Gram-negative bacteria, MsbA and LptB₂FGC work together to translocate lipopolysaccharide (LPS) (Doerrler et al., 2001; Ghanei et al., 2007), while in Gram-positive bacteria, the ABC exporter (TarGH) promotes export of teichoic acids, which make up peptidoglycans in the cell wall. Teichoic acids not only protect the bacteria from phagocytosis but also act as an adhesin that is conducive to bacterial adherence (França et al., 2021; Pietrocola et al., 2022). Figures created with BioRender.com.