Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection.
Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection.
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DOI：
10.1128/mbio.01114-21
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发表时间：
2021-08-31
期刊：
影响因子：
6.4
通讯作者：
Mobley HLT
中科院分区：
文献类型：
--
作者：
Anderson MT;Brown AN;Pirani A;Smith SN;Photenhauer AL;Sun Y;Snitkin ES;Bachman MA;Mobley HLT
由于高死亡率和治疗费用，血流感染（BSI）是一个主要的公共卫生负担。与这些感染相关的革兰氏阴性菌中抗生素耐药性的增加进一步加剧了BSI的影响。大肠杆菌、粘质沙雷氏菌、肺炎克雷伯氏菌、霍氏肠杆菌、弗氏柠檬酸杆菌和鲍曼不动杆菌都是BSI的常见病因，可在鼠模型中重现。本研究的目的是表征这六种病原体菌血症期间的感染动力学和细菌复制率，以更好地了解感染期间的细菌生理学。对供试种属细菌负荷的时间观察表明，在脾脏、肝脏或肾脏中建立定植的能力各不相同。K.肺炎链球菌和S.粘质杆菌分别在肝脏和肾脏中迅速扩张。其他生物，如C。freundii和E. Hormaechei在整个感染过程中从所有三个靶器官中稳定清除。通过对从小鼠脾脏中回收的细菌DNA进行全基因组测序测量的原位复制率表明，每个物种都能够在感染后24小时持续复制，并且有几个物种的世代时间<60分钟。在脾脏中观察到的相对较短的世代时间与某些种属的细菌负荷总体下降形成对比，表明免疫介导的清除率超过了复制。此外，在小鼠脾脏中测量的细菌生成时间接近在人血清培养物中生长期间测量的时间。总之，这些发现提供了深入了解六个医学上重要的物种在菌血症期间的感染动力学。
Bloodstream infections (BSI) are a major public health burden due to high mortality rates and the cost of treatment. The impact of BSI is further compounded by a rise in antibiotic resistance among Gram-negative species associated with these infections. Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter hormaechei, Citrobacter freundii, and Acinetobacter baumannii are all common causes of BSI, which can be recapitulated in a murine model. The objective of this study was to characterize infection kinetics and bacterial replication rates during bacteremia for these six pathogens to gain a better understanding of bacterial physiology during infection. Temporal observations of bacterial burdens of the tested species demonstrated varied abilities to establish colonization in the spleen, liver, or kidney. K. pneumoniae and S. marcescens expanded rapidly in the liver and kidney, respectively. Other organisms, such as C. freundii and E. hormaechei, were steadily cleared from all three target organs throughout the infection. In situ replication rates measured by whole-genome sequencing of bacterial DNA recovered from murine spleens demonstrated that each species was capable of sustained replication at 24 h postinfection, and several species demonstrated <60-min generation times. The relatively short generation times observed in the spleen were in contrast to an overall decrease in bacterial burden for some species, suggesting that the rate of immune-mediated clearance exceeded replication. Furthermore, bacterial generation times measured in the murine spleen approximated those measured during growth in human serum cultures. Together, these findings provide insight into the infection kinetics of six medically important species during bacteremia.