Targeted dose delivery of Mycobacterium tuberculosis in mice using silicon antifoaming agent via aerosol exposure system.
Targeted dose delivery of Mycobacterium tuberculosis in mice using silicon antifoaming agent via aerosol exposure system.
复制标题
DOI：
10.1371/journal.pone.0276130
复制
发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
结核分枝杆菌（Mtb）是一种细胞内病原体，在固体琼脂平板和液体培养基中形成聚集体（团块）。去污剂如吐温80/泰洛沙泊被认为是破坏Mtb培养物中团块形成的金标准。然而，洗涤剂的存在可能产生泡沫并阻碍Mtb气溶胶化，因此需要添加消泡剂以用于最佳的基于Mtb气溶胶的程序。气雾剂吸入在技术上具有挑战性，特别是要达到可重复的吸入目标剂量。在这项研究中，消泡剂，硅消泡剂（SAF），对结核分枝杆菌气溶胶和全身小鼠气溶胶感染的影响进行了研究。在含有牛分枝杆菌BCG（M. bovis BCG）或Mtb H37 Rv对细菌活力没有任何不利影响。在分枝杆菌吸入过程中加入SAF表明，雾化的分枝杆菌菌株保持在受控的环境条件下，如湿度、温度、压力和气溶胶室内的气流。此外，环境因素和喷雾因素不受影响的存在SAF的分枝杆菌培养物在雾化。与高剂量分枝杆菌相比，低剂量分枝杆菌气雾剂程序期间的喷雾因子显著更小，正如预测的那样。生物采样器（AGI）中回收的分枝杆菌载量比雾化器或输入细菌载量低约2-3 log。在小鼠肺中测定的一致的Mtb杆菌负荷表明SAF在气溶胶产生过程中不影响分枝杆菌气溶胶化。这些数据证实：1）SAF可防止雾化过程中形成过量泡沫，2）SAF对气溶胶液滴内的分枝杆菌活力无负面影响，3）气溶胶生成颗粒内的Mtb液滴完全在达到并沉积到肺组织深处所需的范围内，以及4）SAF对暴露于Mtb气溶胶的小鼠达到目标剂量无负面影响。
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that forms aggregates (clumps) on solid agar plates and in liquid media. Detergents such as Tween 80/Tyloxapol are considered the gold standard to disrupt clump formation in Mtb cultures. The presence of detergent, however, may generate foam and hinder Mtb aerosolization thus requiring addition of an antifoam agent for optimal Mtb aerosol-based procedures. Aerosol inhalation can be technically challenging, in particular to achieve a reproducible inhaled target dose. In this study, the impact of an antifoam, the silicon antifoaming agent (SAF), on Mtb aerosolization and whole-body mouse aerosol infection was investigated. A comparative study using SAF in a liquid suspension containing Mycobacterium bovis BCG (M. bovis BCG) or Mtb H37Rv did not cause any adverse effect on bacterial viability. Incorporation of SAF during mycobacteria inhalation procedures revealed that aerosolized mycobacterial strains were maintained under controlled environmental conditions such as humidity, temperature, pressure, and airflow inside the aerosol chamber. In addition, environmental factors and spray factors were not affected by the presence of SAF in mycobacterial cultures during aerosolization. Spray factor was significantly less during aerosol procedures with a low-input dose of mycobacteria in comparison to high-dose, as predicted. The mycobacterial load recovered in the biosampler (AGI) was ~2–3 logs lower than nebulizer or input bacterial load. A consistent Mtb bacillary load determined in mouse lungs indicates that SAF does not affect mycobacteria aerosolization during the aerosol generation process. These data confirmed that 1) SAF prevents formation of excessive foam during aerosolization, 2) SAF had no negative impact on mycobacterial viability within aerosol droplets, 3) Mtb droplets within aerosol-generated particles are well within the range required for reaching and depositing deep into lung tissue, and 4) SAF had no negative impact on achieving a target dose in mice exposed to Mtb aerosol.
登录
查看更多内容
影响因子：
3.7
作者：
Gautam US;Mehra S;Kaushal D
通讯作者：
Kaushal D
影响因子：
11.4
作者：
Hamming, Ole J.;Terczynska-Dyla, Ewa;Vieyres, Gabrielle;Dijkman, Ronald;Jorgensen, Sanne E.;Akhtar, Hashaam;Siupka, Piotr;Pietschmann, Thomas;Thiel, Volker;Hartmann, Rune
通讯作者：
Hartmann, Rune
影响因子：
3.3
作者：
BRECEVIC, L;BOSANKILIBARDA, I;STRAJNAR, F
通讯作者：
STRAJNAR, F
DOI：
10.1016/j.vascn.2003.07.001
发表时间：
2004-01-01
影响因子：
1.9
作者：
Hartings, Justin M.;Roy, Chad J.
通讯作者：
Roy, Chad J.
影响因子：
3.2
作者：
BELISLE, JT;BRENNAN, PJ
通讯作者：
BRENNAN, PJ