Cell density-dependent antibiotic tolerance to inhibition of the elongation machinery requires fully functional PBP1B.
Cell density-dependent antibiotic tolerance to inhibition of the elongation machinery requires fully functional PBP1B.
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DOI：
10.1038/s42003-022-03056-x
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发表时间：
2022-02-03
影响因子：
5.9
通讯作者：
Morgenstein RM
中科院分区：
文献类型：
--
作者：
Grinnell A;Sloan R;Morgenstein RM
肽聚糖(PG)细胞壁为大多数细菌提供了形状和结构。在杆状生物体中有两个构建PG的系统：伸长体和分裂体，它们分别由许多蛋白质组成，包括必需的MreB和PBP2，或FtsZ和PBP3。伸长体负责细胞伸长过程中PG的插入，而分裂体负责细胞分裂过程中隔膜PG的插入。我们发现，主要的伸长体蛋白MreB和PBP2可以被抑制，而不影响生长速度，这种抑制方式不依赖于群体感应和密度。在细胞达到特定的细胞密度之前，抑制伸长体会导致不同的生理反应，包括细胞内小泡的形成和细胞大小的增加。这种对MreB或PBP2的抑制可以通过A类青霉素结合蛋白PBP1B的存在来补偿。此外，我们发现这种密度依赖的生长耐药性是针对细长体抑制的，并且在多个革兰氏阴性杆菌中是一致的，这为抗生素治疗提供了新的研究领域。Grinnell et.Al报道了一种依赖于细胞密度的杆状细菌对抗生素耐受性的新机制，该机制专门针对细胞壁延长系统。他们的发现表明，同时破坏伸长体和分裂体可能是克服密度依赖生长抗性的有效方法。
The peptidoglycan (PG) cell wall provides shape and structure to most bacteria. There are two systems to build PG in rod shaped organisms: the elongasome and divisome, which are made up of many proteins including the essential MreB and PBP2, or FtsZ and PBP3, respectively. The elongasome is responsible for PG insertion during cell elongation, while the divisome is responsible for septal PG insertion during division. We found that the main elongasome proteins, MreB and PBP2, can be inhibited without affecting growth rate in a quorum sensing-independent density-dependent manner. Before cells reach a particular cell density, inhibition of the elongasome results in different physiological responses, including intracellular vesicle formation and an increase in cell size. This inhibition of MreB or PBP2 can be compensated for by the presence of the class A penicillin binding protein, PBP1B. Furthermore, we found this density-dependent growth resistance to be specific for elongasome inhibition and was consistent across multiple Gram-negative rods, providing new areas of research into antibiotic treatment. Grinnell et. al report a new mechanism of antibiotic tolerance in rod-shaped bacteria that is dependent on cell density and which specifically targets the cell wall elongation system. Their findings suggest that simultaneous disruption of both the elongasome and the divisome may be an efficient way of overcoming density-dependent growth resistance.
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DOI：
10.1073/pnas.1400376111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Egan, Alexander J. F.;Jean, Nicolas L.;Simorre, Jean-Pierre
通讯作者：
Simorre, Jean-Pierre
影响因子：
3.2
作者：
ALDEA, M;HERNANDEZCHICO, C;VICENTE, M
通讯作者：
VICENTE, M
影响因子：
4.9
作者：
Falagas, ME;McDermott, L;Snydman, DR
通讯作者：
Snydman, DR
影响因子：
5.2
作者：
Barton B;Grinnell A;Morgenstein RM
通讯作者：
Morgenstein RM
DOI：
10.1073/pnas.74.11.5104
发表时间：
1977-01-01
影响因子：
11.1
作者：
ACHTMAN, M;KENNEDY, N;SKURRAY, R
通讯作者：
SKURRAY, R