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

鉴定抑制脂多糖转运蛋白LptD缺失介导的致死率和抗生素敏感性的遗传和环境因素

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Abstract

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 lptD mutant. The lethality of the lptD mutant was weakened under acidic or salt stress conditions, as well as by the deletion of the ygfB gene encoding a hypothetical protein or the aceE 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 aceE or ygfB. Collectively, these results can improve our understanding of the physiological functions and clinical importance of LptD.

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