Corseting a tripartite ABC transporter to make it fit for transport

The assembly and efflux processes revealed byin situstructures of the ABC-type tripartite pump MacAB-TolC

“…In this study, we show the in situ structures of the MacAB-TolC efflux pump in E. coli, both in native and erythromycin-present states. Combining imaging results, protein crosslinking data, as well as previous works 10,12,14,15 , we propose a model for the in situ assembly and working mechanism of MacAB-TolC (Figure 4). Without substrates (apo state), MacA and TolC are highly likely to associate to form a stable bipartite complex in the cell.…”

Resistance mechanisms of tigecycline in Acinetobacter baumannii

“…In summary, A. baumannii can produce resistance to tigecycline through RND efflux pumps (AdeABC, AdeFGH, AdeIJK) ( Magnet et al., 2001 ; Damier-Piolle et al., 2008 ; Coyne et al., 2010b ), MATE family (AbeM) ( Su et al., 2005 ), ABC transporters (MsbA, MacAB-TolC) ( Shilling et al., 2006 ; Batista Dos Santos et al., 2022 ), and MFS efflux pumps (TetA, TetB, TetA(39), Tet (Y)) ( Rumbo et al., 2013 ; Wang et al., 2021 ; Jagdmann et al., 2022 ; Khlaif and Hussein, 2022 ). In addition, A. baumannii also reduces membrane permeability (plsc, abrp, gnaA, abuO) ( Lu et al., 2005 ; Wang et al., 2012 ; Srinivasan et al., 2015 ; Li et al., 2016 ), alters antibiotic targets (rpsJ, trm, rrf, rpoB) ( Ma et al., 2014 ; Beabout et al., 2015 ; Hua et al., 2021 ; Ghalavand et al., 2022 ), produces tigecycline inactivating enzymes (Tet(X) and its variants Tet (X3), Tet(X5), Tet(X6)) ( Moore et al., 2005 ; He et al., 2019 ; Chen et al., 2021 ) and DNA repair pathways (recA and recBCD) ( Kuzminov, 1999 ; Aranda et al., 2011 ) mediating tigecycline resistance.…”

“…Prototypical member of Type VII ABC transporter superfamily (Batista Dos Santos et al, 2022) MFS efflux pumps tetA Encode the TetA efflux pump (Jagdmann et al, 2022) tetB Encode the TetB efflux pump (Khlaif and Hussein, 2022) tetA(39) Encode the TetA(39) efflux pump (Rumbo et al, 2013) tet (Y) Encode the Tet(Y) efflux pump (Wang et al, 2021) Regulatory factors tetR TetR-family transcriptional regulators (Sumyk et al, 2021) baeSR Two-component regulatory system consisting of a sensor histidine kinase (HK) and a cytoplasmic response regulator (RR) (Leblanc et al, 2011) adeN TetR-like transcription regulator (Rosenfeld et al, 2012) adeL LysR-type transcription regulator (Coyne et al, 2010b) soxR global regulator (Li et al, 2017) Outer membrane permeability plsC Encode lysophosphatidic acid acyltransferase (Lu et al, 2005) abrp Encode the peptidase C13 family (Li et al, 2016) gnaA Encode a UDP-GlcNAc 6-dehydrogenase (Wang et al, 2012) abuO A TolC-like outer membrane protein (Srinivasan et al, 2015) Antibiotic targets of action rpsJ Encode the ribosomal S10 protein (Beabout et al, 2015) trm Encode S-adenosyl-L-methionine-dependent methyltransferase (Ghalavand et al, 2022) rrf Encode ribosome recycling factor (Ma et al, 2014) rpoB RNA polymerase b-subunit (Cao et al, 2022) Antibiotic-inactivating enzyme tet(X) Encode flavin-dependent monooxygenase (Moore et al, 2005) tet(X3) Plasmid-mediated Tet(X)-variant Tet(X3) (He et al, 2019) tet(X5) Plasmid-mediated Tet(X)-variant Tet(X5) (Wang et al, 2019) tet(X6) Plasmid-mediated Tet(X)-variant Tet(X6) (Zheng et al, 2020) DNA repair pathway recA Major enzyme involved in homologous genetic recombination and recombinational repair (Aranda et al, 2011) recBCD Recombinational repair pathway, repair of DNA double-strand breaks (Kuzminov, 1999) minimum inhibitory concentration (MIC) of tigecycline (Yuhan et al, 2016). Privita et al demonstrated the essential role of adeC in the AdeABC efflux pump by inhibiting adeC and achieving complete blockage of the efflux process when designing a potent inhibitor of the AdeABC efflux pump against A. baumannii (Verma and Tiwari, 2018).…”

ABC Transporters in Bacterial Nanomachineries

“…In 2021, Souabni et al determined a transport rate of three molecules per hydrolyzed ATP molecule for the substrate roxithromycin [ 23 ]. Recently, Batista dos Santos et al [ 49 ] showed that the presence of TolC increases MacB ATPase activity in detergent as well as in lipid nanodiscs. Furthermore, they could also show a substrate-induced increase in MacB ATPase activity for the fully assembled MacAB-TolC system in a lipid environment [ 49 ].…”