Structural and functional analysis of the Helicobacter pylori lipoprotein chaperone LolA

Lipoproteins are crucial for maintaining the structural integrity of bacterial membranes. In Gram-negative bacteria, the localization of lipoprotein (Lol) system facilitates the transport of these proteins from the inner membrane to the outer membrane. In <i>Helicobacter pylori</i>, an ε-proteobacterium, lipoprotein transport differs significantly from the canonical and well-studied system in <i>Escherichia coli</i>, particularly due to the absence of LolB and the use of a LolF homodimer instead of the LolCE heterodimer. This study presents the crystal structure of the <i>H. pylori</i> lipoprotein chaperone LolA (LolA-HP) and its interaction with lipopeptide antibiotics such as polymyxin B and colistin. Isothermal titration calorimetry revealed that, unlike LolA from <i>Vibrio cholerae</i> and <i>Porphyromonas gingivalis</i>, LolA-HP does not bind to these antibiotics. Structural comparisons showed that LolA-HP has a deeper hydrophobic cleft but lacks the negative electrostatic potential critical for binding polymyxins. These findings offer insights into the structural diversity of LolA across bacterial species and its potential as a target for antibacterial agents.