Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury.
Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury.
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DOI：
10.1038/srep39341
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发表时间：
2016-12-20
影响因子：
4.6
通讯作者：
Krachler AM
中科院分区：
文献类型：
--
作者：
Huebinger RM;Stones DH;de Souza Santos M;Carlson DL;Song J;Vaz DP;Keen E;Wolf SE;Orth K;Krachler AM
经典的抗微生物药物以增殖为目标，因此使微生物处于极端的选择压力下进化出耐药性。针对细菌毒力而不直接影响生存的替代药物为这个问题提供了一个有吸引力的解决方案，但迄今为止，这样的分子还很少被发现。我们之前发现了一组广泛存在的细菌粘附素，称为多价粘附分子（MAMs），它们对于细菌与宿主组织的初始结合和毒性至关重要。因此，靶向基于mam的粘附是一种很有前途的策略，可以从宿主组织中取代病原体并抑制感染。本研究表明，局部应用黏附素MAM7功能化的聚合物微珠治疗多药耐药铜绿假单胞菌感染烧伤，可显著减少伤口细菌负荷，防止感染向邻近组织扩散。因此，这种粘附抑制剂的应用允许血管化和伤口愈合，并维持局部和全身对烧伤的炎症反应。我们建议mam7功能化的微珠可以用作局部治疗，以减少细菌附着，从而防止细菌定植和伤口感染。由于黏附不是微生物生存所必需的，这种抗感染策略具有治疗多重耐药感染和限制耐药病原体出现的潜力。
Classical antimicrobial drugs target proliferation and therefore place microbes under extreme selective pressure to evolve resistance. Alternative drugs that target bacterial virulence without impacting survival directly offer an attractive solution to this problem, but to date few such molecules have been discovered. We previously discovered a widespread group of bacterial adhesins, termed Multivalent Adhesion Molecules (MAMs) that are essential for initial binding of bacteria to host tissues and virulence. Thus, targeting MAM-based adherence is a promising strategy for displacing pathogens from host tissues and inhibiting infection. Here, we show that topical application of polymeric microbeads functionalized with the adhesin MAM7 to a burn infected with multidrug-resistant Pseudomonas aeruginosa substantially decreased bacterial loads in the wound and prevented the spread of the infection into adjacent tissues. As a consequence, the application of this adhesion inhibitor allowed for vascularization and wound healing, and maintained local and systemic inflammatory responses to the burn. We propose that MAM7-functionalized microbeads can be used as a topical treatment, to reduce bacterial attachment and hence prevent bacterial colonization and infection of wounds. As adhesion is not required for microbial survival, this anti-infective strategy has the potential to treat multidrug-resistant infections and limit the emergence of drug-resistant pathogens.
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影响因子：
4.8
作者：
Krachler, Anne Marie;Orth, Kim
通讯作者：
Orth, Kim
影响因子：
6.7
作者：
Lim, Jenson;Stones, Daniel H.;Krachler, Anne Marie
通讯作者：
Krachler, Anne Marie
DOI：
10.3791/53400
发表时间：
2015-11-16
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Stones DH;Al-Saedi F;Vaz D;Perez-Soto N;Krachler AM
通讯作者：
Krachler AM
影响因子：
20.3
作者：
BitMansour, A;Burns, SM;Brown, JMY
通讯作者：
Brown, JMY
DOI：
10.1097/00004630-199505000-00002
发表时间：
1995-01-01
期刊：
Journal of Burn Care and Rehabilitation
影响因子：
--
作者：
Saffle, Jeffrey R.;Davis, Byron;Group, American Burn Association Registry Participant
通讯作者：
Group, American Burn Association Registry Participant