Inter-species interactions alter antibiotic efficacy in bacterial communities.
Inter-species interactions alter antibiotic efficacy in bacterial communities.
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DOI：
10.1038/s41396-021-01130-6
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Friman VP
中科院分区：
文献类型：
--
作者：
Bottery MJ;Matthews JL;Wood AJ;Johansen HK;Pitchford JW;Friman VP
基于单培养中最低抑菌浓度（MIC）测定的常规体外药敏试验，不能很好地预测针对多微生物群落的抗生素治疗效果。原因之一是种间相互作用会改变群落成员对抗生素的敏感性。在此，我们对来自临床样本的囊性纤维化（CF）肺部模型群落中，临床相关抗生素对病原体铜绿假单胞菌疗效的群落调节变化进行量化，并确定其机制。我们证明，多重耐药的嗜麦芽窄食单胞菌能为原本敏感的铜绿假单胞菌提供高水平的抗生素保护。亚胺培南的暴露保护是由染色体编码的金属β -内酰胺酶提供的，该酶可净化环境；这种保护取决于嗜麦芽窄食单胞菌的细胞密度，并且由从CF痰液中分离出的嗜麦芽窄食单胞菌菌株提供，可使铜绿假单胞菌的MIC提高多达16倍。相比之下，嗜麦芽窄食单胞菌的存在对美罗培南（另一种常规使用的碳青霉烯类抗生素）没有保护作用。数学常微分方程模型表明，针对不同碳青霉烯类抗生素提供的暴露保护水平可以通过抗生素疗效和失活速率的差异来解释。总之，这些发现表明，利用预先存在的抗菌耐药性以及种间竞争，会对病原体的抗生素敏感性产生重大影响，突出了微生物生态学对于设计针对多物种群落的成功抗生素治疗方案的重要性。
The efficacy of antibiotic treatments targeting polymicrobial communities is not well predicted by conventional in vitro susceptibility testing based on determining minimum inhibitory concentration (MIC) in monocultures. One reason for this is that inter-species interactions can alter the community members’ susceptibility to antibiotics. Here we quantify, and identify mechanisms for, community-modulated changes of efficacy for clinically relevant antibiotics against the pathogen Pseudomonas aeruginosa in model cystic fibrosis (CF) lung communities derived from clinical samples. We demonstrate that multi-drug resistant Stenotrophomonas maltophilia can provide high levels of antibiotic protection to otherwise sensitive P. aeruginosa. Exposure protection to imipenem was provided by chromosomally encoded metallo-β-lactamase that detoxified the environment; protection was dependent upon S. maltophilia cell density and was provided by S. maltophilia strains isolated from CF sputum, increasing the MIC of P. aeruginosa by up to 16-fold. In contrast, the presence of S. maltophilia provided no protection against meropenem, another routinely used carbapenem. Mathematical ordinary differential equation modelling shows that the level of exposure protection provided against different carbapenems can be explained by differences in antibiotic efficacy and inactivation rate. Together, these findings reveal that exploitation of pre-occurring antimicrobial resistance, and inter-specific competition, can have large impacts on pathogen antibiotic susceptibility, highlighting the importance of microbial ecology for designing successful antibiotic treatments for multispecies communities.
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细菌群落抗菌素耐药性的生态学和进化。
DOI：
10.1038/s41396-020-00832-7
发表时间：
2021-04
期刊：
The ISME journal
影响因子：
--
作者：
Bottery MJ;Pitchford JW;Friman VP
通讯作者：
Friman VP
影响因子：
5.2
作者：
Dalboge, C. S.;Hansen, C. R.;Johansen, H. K.
通讯作者：
Johansen, H. K.
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
影响因子：
5.2
作者：
Andrews, JM
通讯作者：
Andrews, JM
影响因子：
16.6
作者：
Bricio-Moreno L;Sheridan VH;Goodhead I;Armstrong S;Wong JKL;Waters EM;Sarsby J;Panagiotou S;Dunn J;Chakraborty A;Fang Y;Griswold KE;Winstanley C;Fothergill JL;Kadioglu A;Neill DR
通讯作者：
Neill DR