Layered and integrated medical countermeasures against Burkholderia pseudomallei infections in C57BL/6 mice.
Layered and integrated medical countermeasures against Burkholderia pseudomallei infections in C57BL/6 mice.
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针对C57BL/6小鼠的Burkholderia Pseudomallei感染的分层和综合的医学对策。
DOI：
10.3389/fmicb.2022.965572
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
假鼻疽伯克霍尔德氏菌是一种引起类鼻疽的革兰氏阴性细菌，众所周知，它很难用抗生素治疗。一项重大努力侧重于确定预防类鼻疽病的保护性疫苗战略。然而，当作为单独的医学对策使用时，抗生素治疗(治疗或暴露后预防)和实验性疫苗策略仍然具有部分保护作用。在这里，我们证明，当联合使用时，当前的疫苗策略(重组蛋白亚基AhpC和/或Hcp1加上与CRM197或减毒活疫苗B.Posomallei668ΔILVI结合的衣壳多糖)和联合新诺明方案可以在类鼻疽小鼠模型中产生近乎一致的保护，因为与不同的药物对策相关联的明显的协同作用。我们的结果在检查几种不太理想的抗生素方案(例如，感染后早期开始的7天抗生素疗程或延迟开始的21天抗生素疗程)时显示出显著的改善。重要的是，当对蛋白质亚单位或减毒活疫苗进行评估时，这种组合策略的效果相似。分层和综合的医学对策将为类鼻疽病以及其他病原体引起的疾病提供新的治疗选择，这些疾病对个别策略难以奏效，特别是在工程、新兴或重新出现的细菌生物治疗剂的情况下。
Burkholderia pseudomallei, the gram-negative bacterium that causes melioidosis, is notoriously difficult to treat with antibiotics. A significant effort has focused on identifying protective vaccine strategies to prevent melioidosis. However, when used as individual medical countermeasures both antibiotic treatments (therapeutics or post-exposure prophylaxes) and experimental vaccine strategies remain partially protective. Here we demonstrate that when used in combination, current vaccine strategies (recombinant protein subunits AhpC and/or Hcp1 plus capsular polysaccharide conjugated to CRM197 or the live attenuated vaccine strain B. pseudomallei 668 ΔilvI) and co-trimoxazole regimens can result in near uniform protection in a mouse model of melioidosis due to apparent synergy associated with distinct medical countermeasures. Our results demonstrated significant improvement when examining several suboptimal antibiotic regimens (e.g., 7-day antibiotic course started early after infection or 21-day antibiotic course with delayed initiation). Importantly, this combinatorial strategy worked similarly when either protein subunit or live attenuated vaccines were evaluated. Layered and integrated medical countermeasures will provide novel treatment options for melioidosis as well as diseases caused by other pathogens that are refractory to individual strategies, particularly in the case of engineered, emerging, or re-emerging bacterial biothreat agents.
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影响因子：
5.6
作者：
Antonelli G;Cappelli L;Cinelli P;Cuffaro R;Manca B;Nicchi S;Tondi S;Vezzani G;Viviani V;Delany I;Scarselli M;Schiavetti F
通讯作者：
Schiavetti F
影响因子：
4.9
作者：
Biron, Bethany;Beck, Katie;Nalca, Aysegul
通讯作者：
Nalca, Aysegul
影响因子：
2.8
作者：
Bernhards, R. C.;Cote, C. K.;Welkos, S. L.
通讯作者：
Welkos, S. L.
影响因子：
3.9
作者：
Almaaytah A;Qaoud MT;Abualhaijaa A;Al-Balas Q;Alzoubi KH
通讯作者：
Alzoubi KH
DOI：
10.1016/j.ijantimicag.2013.02.007
发表时间：
2013-06-01
影响因子：
10.8
作者：
Barnes, Kay B.;Steward, Jackie;Atkins, Helen S.
通讯作者：
Atkins, Helen S.