Burkholderia pseudomallei is an environmental bacterium that causes melioidosis, a major community-acquired infection in tropical regions. Melioidosis presents with a range of clinical symptoms, is often characterized by a robust inflammatory response, may relapse after treatment, and results in high mortality rates. Lipopolysaccharide (LPS) of B. pseudomallei is a potent immunostimulatory molecule comprised of lipid A, core, and O-polysaccharide (OPS) components. Four B. pseudomallei LPS types have been described based on SDS-PAGE patterns that represent the difference of OPS–type A, type B, type B₂ and rough LPS. The majority of B. pseudomallei isolates are type A. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) followed by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QqTOF MS) and gas chromatography to characterize the lipid A of B. pseudomallei within LPS type A isolates. We determined that B. pseudomallei lipid A is represented by penta- and tetra-acylated species modified with 4-amino-4-deoxy-arabinose (Ara4N). The MALDI-TOF profiles from 171 clinical B. pseudomallei isolates, including 68 paired primary and relapse isolates and 35 within-host isolates were similar. We did not observe lipid A structural changes when the bacteria were cultured in different growth conditions. Dose-dependent NF-κB activation in HEK cells expressing TLR4 was observed using multiple heat-killed B. pseudomallei isolates and corresponding purified LPS. We demonstrated that TLR4-dependent NF-κB activation induced by heat-killed bacteria or LPS prepared from OPS deficient mutant was significantly greater than those induced by wild type B. pseudomallei. These findings suggest that the structure of B. pseudomallei lipid A is highly conserved in a wide variety of clinical and environmental circumstances but that the presence of OPS may modulate LPS-driven innate immune responses in melioidosis.

假伯克霍尔德氏菌是一种环境细菌，可导致类鼻oid病，这是热带地区主要的社区获得性感染。痔疮表现出一系列临床症状，通常以强烈的炎症反应为特征，在治疗后可能复发，并导致高死亡率。B的脂多糖（LPS）。假马来酸是一种有效的免疫刺激分子，由脂质A，核心和O-多糖（OPS）组成。四乙。基于SDS-PAGE模式描述了假苹果油LPS类型，SDS-PAGE模式代表了OPS类型A，类型B，类型B ₂和粗略LPS的差异。B的大多数。假苹果分离物是A型。我们使用基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS），然后使用电喷雾电离四极杆飞行时间质谱（ESI-QqTOF MS）和气相色谱法进行表征的脂质A乙。LPS A型内的假苹果芽孢杆菌分离。我们确定了乙。杆菌脂质A是由五-表示，并且修改与4-氨基-4-脱氧阿拉伯糖（Ara4N）四酰化物质。来自171个临床B的MALDI-TOF图谱。假苹果分离株包括68个配对的原发和复发分离株以及35个寄主内分离株相似。当细菌在不同的生长条件下培养时，我们没有观察到脂质A的结构变化。使用多个热灭活的B观察到表达TLR4的HEK细胞中剂量依赖性的NF-κB活化。假苹果分离物和相应的纯化的LPS。我们证明，由OPS缺陷型突变体制备的热灭活细菌或LPS诱导的TLR4依赖性NF-κB激活明显大于野生型B诱导的激活。假马来虫。这些发现表明B的结构。假苹果 脂质A在各种临床和环境条件下都是高度保守的，但是OPS的存在可能会调节类li虫病中LPS驱动的先天免疫应答。