Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA.
Center for Science & Engineering of Living Systems (CSELS), McKelvey School of Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
mBio. 2020 Oct 13;11(5):e02456-20. doi: 10.1128/mBio.02456-20.
Single-celled organisms must adapt their physiology to persist and propagate across a wide range of environmental conditions. The growth and division of bacterial cells depend on continuous synthesis of an essential extracellular barrier: the peptidoglycan cell wall, a polysaccharide matrix that counteracts turgor pressure and confers cell shape. Unlike many other essential processes and structures within the bacterial cell, the peptidoglycan cell wall and its synthesis machinery reside at the cell surface and are thus uniquely vulnerable to the physicochemical environment and exogenous threats. In addition to the diversity of stressors endangering cell wall integrity, defects in peptidoglycan metabolism require rapid repair in order to prevent osmotic lysis, which can occur within minutes. Here, we review recent work that illuminates mechanisms that ensure robust peptidoglycan metabolism in response to persistent and acute environmental stress. Advances in our understanding of bacterial cell wall quality control promise to inform the development and use of antimicrobial agents that target the synthesis and remodeling of this essential macromolecule. Nearly all bacteria are encased in a peptidoglycan cell wall, an essential polysaccharide structure that protects the cell from osmotic rupture and reinforces cell shape. The integrity of this protective barrier must be maintained across the diversity of environmental conditions wherein bacteria replicate. However, at the cell surface, the cell wall and its synthesis machinery face unique challenges that threaten their integrity. Directly exposed to the extracellular environment, the peptidoglycan synthesis machinery encounters dynamic and extreme physicochemical conditions, which may impair enzymatic activity and critical protein-protein interactions. Biotic and abiotic stressors-including host defenses, cell wall active antibiotics, and predatory bacteria and phage-also jeopardize peptidoglycan integrity by introducing lesions, which must be rapidly repaired to prevent cell lysis. Here, we review recently discovered mechanisms that promote robust peptidoglycan synthesis during environmental and acute stress and highlight the opportunities and challenges for the development of cell wall active therapeutics.
单细胞生物必须适应其生理学，以在广泛的环境条件下生存和繁殖。细菌细胞的生长和分裂依赖于持续合成一种必需的细胞外屏障：肽聚糖细胞壁，这是一种多糖基质，可抵抗膨压并赋予细胞形状。与细菌细胞内的许多其他必需过程和结构不同，肽聚糖细胞壁及其合成机制位于细胞表面，因此对外界环境和外来威胁具有独特的易感性。除了威胁细胞壁完整性的各种压力源外，肽聚糖代谢缺陷需要快速修复，以防止渗透裂解，这种情况可能在几分钟内发生。在这里，我们回顾了最近的工作，这些工作阐明了确保肽聚糖代谢在应对持续和急性环境压力时具有稳健性的机制。我们对细菌细胞壁质量控制的理解的进展有望为靶向这种必需大分子的合成和重塑的抗菌剂的开发和使用提供信息。几乎所有细菌都被包裹在肽聚糖细胞壁中，这是一种保护细胞免受渗透破裂和增强细胞形状的必需多糖结构。在细菌复制的各种环境条件下，必须保持这种保护屏障的完整性。然而，在细胞表面，细胞壁及其合成机制面临着独特的挑战，这些挑战威胁着它们的完整性。直接暴露于细胞外环境，肽聚糖合成机制会遇到动态和极端的物理化学条件，这可能会损害酶活性和关键的蛋白质-蛋白质相互作用。生物和非生物胁迫因素，包括宿主防御、细胞壁活性抗生素以及捕食细菌和噬菌体，也会通过引入损伤来威胁肽聚糖的完整性，这些损伤必须迅速修复以防止细胞裂解。在这里，我们回顾了最近发现的促进环境和急性应激下肽聚糖合成的稳健性的机制，并强调了开发细胞壁活性治疗剂的机会和挑战。
