Identification of Genetic and Environmental Factors Suppressing the Lethality and Antibiotic Susceptibility Mediated by Depletion of LptD, a Lipopolysaccharide Transport Protein

Lipopolysaccharide (LPS), an essential component of the outer membrane (OM) of Gram-negative bacteria, is transported through dedicated Lpt machinery consisting of seven essential proteins. LptD is an OM protein with a β-barrel structure and is involved in the insertion of LPS into the outer leaflet of the OM. In this study, we identified several genetic and environmental factors that partially suppress the lethality and antibiotic susceptibility of the <i>lptD</i> mutant. The lethality of the <i>lptD</i> mutant was weakened under acidic or salt stress conditions, as well as by the deletion of the <i>ygfB</i> gene encoding a hypothetical protein or the <i>aceE</i> gene encoding pyruvate dehydrogenase. YgfB physically interacted with the phosphatidylserine synthase PssA, implying that YgfB may be involved in phospholipid biosynthesis. Decreased expression of LptD strongly increased susceptibility to several antibiotics, such as clindamycin and rifampicin, and these increased susceptibilities were partially weakened by the deletion of <i>aceE</i> or <i>ygfB</i>. Collectively, these results can improve our understanding of the physiological functions and clinical importance of LptD.