Department of Plant Sciences, School of Life Sciences, University of Hyderabad, P.O. Central University, Hyderabad, 500 046, India; National Centre for Microbial Resource, National Centre for Cell Science, Pune, 411011, India.
Department of Plant Sciences, School of Life Sciences, University of Hyderabad, P.O. Central University, Hyderabad, 500 046, India.
Microbiol Res. 2019 Jan;218:108-117. doi: 10.1016/j.micres.2018.10.009. Epub 2018 Oct 29.
All three domains of life have an ordered plasma membrane which is pivotal in the selective fitness of primitive life. Like cholesterol in eukaryotes, hopanoids are important in bacteria to modulate membrane order. Hopanoids are pentacyclic triterpenoid lipids biosynthesised in many eubacteria, few ferns and lichens. Hopanoid modulates outer membrane order and hopanoid deficiency results in the weakened structural integrity of the membrane which may in turn affect the other structures within or spanning the cell envelope and contributing to various membrane functions. Hence, to decipher the role of hopanoid, genome-wide transcriptome of wild-type and Δshc mutant of Rhodopseudomonas palustris TIE-1 was studied which indicated 299 genes were upregulated and 306 genes were downregulated in hopanoid deficient mutant, representing ∼11.5% of the genome. Thirty-eight genes involved in chemotaxis, response to stimuli and signal transduction were differentially regulated and impaired motility in hopanoid deficient mutant showed that hopanoid plays a crucial role in chemotaxis. The docking study demonstrated that diguanylate cyclase which catalyses the synthesis of secondary messenger exhibited the capability to interact with hopanoids and might be confederating in chemotaxis and signal transduction. Seventy-four genes involved in membrane transport were differentially expressed and cell assays also explicit that the multidrug transport is compromised in Δshc mutant. Membrane transport is reliant on hopanoids which may explain the basis for previous observations linking hopanoids to antibiotic resistance. Disturbing the membrane order by targeting lipid synthesis can be a possible novel approach in developing new antimicrobials and hopanoid biosynthesis could be a potential target.
所有生命的三个领域都有一个有序的质膜,这对原始生命的选择性适应性至关重要。与真核生物中的胆固醇类似,藿烷类化合物对于调节膜的有序性在细菌中非常重要。藿烷类化合物是许多真细菌、少数蕨类植物和地衣生物合成的五环三萜类脂,藿烷类化合物调节外膜的有序性,藿烷类化合物缺乏会导致膜结构完整性减弱,这反过来又会影响细胞膜内或跨越细胞膜的其他结构,并有助于各种膜功能。因此,为了解析藿烷类化合物的作用,研究了野生型和 Rhodopseudomonas palustris TIE-1 的Δshc 突变体的全基因组转录组,结果表明藿烷类化合物缺乏突变体中有 299 个基因上调,306 个基因下调,约占基因组的 11.5%。涉及趋化作用、对刺激的反应和信号转导的 38 个基因差异调控,藿烷类化合物缺乏突变体的运动能力受损表明藿烷类化合物在趋化作用中起着关键作用。对接研究表明,催化第二信使合成的二鸟苷酸环化酶表现出与藿烷类化合物相互作用的能力,并且可能在趋化作用和信号转导中协同作用。涉及膜转运的 74 个基因差异表达,细胞试验也明确表明,Δshc 突变体中的多药转运受损。膜转运依赖于藿烷类化合物,这可以解释以前观察到的将藿烷类化合物与抗生素抗性联系起来的基础。通过靶向脂质合成扰乱膜秩序可能是开发新抗生素的一种新方法,而藿烷类化合物的生物合成可能是一个潜在的靶点。