LpqY-SugABC trehalose transporter (LpqY-SugABC)

The LpqY-SugABC transporter is a specialized ATP-binding cassette (ABC) transporter in Mycobacterium tuberculosis (Mtb) that mediates the high-affinity uptake and recycling of trehalose (Kalscheuer et al., 2010, PLoS Pathogens). Trehalose is an essential sugar for Mtb, serving as a structural component of the cell wall in the form of mycolic acid esters like trehalose monomycolate (TMM) and trehalose dimycolate (TDM) (UniProt P9WGU7). The transporter complex is composed of the lipoprotein LpqY, which acts as the substrate-binding protein, the transmembrane subunits SugA and SugB, and the ATPase SugC (Kalscheuer et al., 2010). By reclaiming trehalose released during cell wall remodeling, the LpqY-SugABC system supports bacterial persistence and virulence within the host (PubMed: 20628554). Since humans do not possess a homologous trehalose uptake system, this transporter is considered a highly specific therapeutic target for tuberculosis treatment (Zhu et al., 2020, Nature Communications). Experimental inhibitors, such as trehalose analogues, have shown potential in disrupting Mtb growth by blocking this recycling pathway (PubMed: 32612144). The system is also involved in the uptake of other alpha-glycosides, though trehalose is its primary substrate (UniProt P9WGU1). Disruption of the lpqY or sugABC genes leads to significant attenuation of Mtb in infection models, highlighting its importance for pathogenesis (Kalscheuer et al., 2010). Targeting this transporter offers a strategy to bypass traditional antibiotic resistance mechanisms by focusing on essential nutrient recycling (Zhu et al., 2020). Future drug development efforts are focused on small molecules that can competitively bind to LpqY or block the SugA/B channel (PubMed: 32612144).

Other names

Trehalose ABC transporterSugABC-LpqY complexMce4-like transporter system

Competitive inhibition of trehalose binding to the LpqY subunit or blockage of the SugAB transmembrane channel, preventing the recycling of trehalose and disrupting mycobacterial cell wall synthesis.