TtgB Notes

Gene Overview

TtgB (PP_1385, Q88N31) is the inner membrane RND (Resistance-Nodulation-Division) transporter component of the TtgABC tripartite efflux pump in Pseudomonas putida KT2440. It is a 1050 AA protein with 12 predicted transmembrane helices, belonging to the acriflavine resistance protein family (IPR001036) and specifically the MdtF-like subfamily (IPR004764). It is homologous to AcrB in E. coli and MexB in P. aeruginosa.

TtgABC System Architecture

The TtgABC efflux pump is a tripartite system typical of RND family transporters:
- TtgA (PP_1384): Membrane fusion protein (MFP/periplasmic adaptor)
- TtgB (PP_1385): Inner membrane RND transporter (proton-dependent substrate extrusion)
- TtgC (PP_1386): Outer membrane factor (OMF/channel)

The three genes form an operon, transcribed from a single promoter upstream of ttgA. Expression is constitutive but regulated by the TtgR repressor (PP_1387), which is transcribed divergently from ttgA PMID:11251828.

Substrate Specificity and Function

Organic Solvents

In DOT-T1E strain, TtgABC extrudes toluene, styrene, m-xylene, ethylbenzene, and propylbenzene PMID:11395460. However, in KT2440 this operon may not function primarily in toluene efflux [UniProt CAUTION: "In KT2400 this operon does not seem to function in toluene efflux"].

Antibiotics

TtgABC confers resistance to multiple antibiotics in KT2440:
- Chloramphenicol: TtgABC knockout is compromised PMID:22143519
- Fluoroquinolones and beta-lactams: Overexpression of TtgABC via TtgR mutations leads to increased resistance PMID:32840000
- Also quinolones, sulfonamides PMID:24907323
- Indole induces ttgABC expression contributing to ampicillin resistance PMID:28352264

Plant Antimicrobials and Bipyridyls

Multidrug Binding

TtgB itself has been shown to possess multidrug-binding capacity PMID:17498746.

Additional Roles Beyond Efflux

Biofilm Formation

Knockout of ECF-10 sigma factor leads to upregulation of ttgABC and enhanced biofilm formation, suggesting TtgABC plays a role in biofilm development PMID:24907323.

Ion Homeostasis

In the absence of TtgABC, bipyridyl compounds interfere with metal ion homeostasis, affecting copper availability and pyoverdine (siderophore) production PMID:32973714.

Regulatory Context

Key Distinction: KT2440 vs DOT-T1E

The UniProt entry is for KT2440. The caution note indicates that while the homologous system in DOT-T1E functions in solvent efflux, in KT2440 it primarily functions in antibiotic resistance, bipyridyl detoxification, and potentially biofilm formation. The proteins are highly similar but expression levels and ecological context differ.

Homologous Systems

Energy Coupling

Proton-dependent, operates via proton motive force. Energy transfer may involve the TonB system PMID:12142492.

References