Team CanUK: Novel antibacterial targets, assays, probes and opportunities in bacterial cell wall biogenesis

每年有数百万人死于细菌感染，数千万人遭受这些感染的后果。抗生素青霉素的发现曾经打开了治疗这些感染的大门，因为它阻止了细菌在将它们聚集在一起的细胞壁中制造聚合物。这种聚合物被称为肽聚糖，由糖和一串氨基酸(肽)组成的联锁网络组成。有能力将这些糖和多肽结合在一起的特殊蛋白质(称为PBPs)是青霉素抑制的目标，它可以阻止细胞壁的合成并杀死细菌。许多重要的细菌不再被青霉素和其他抗生素杀死，这些抗生素攻击了肽聚糖生产的其他阶段。细菌发生了变化，躲避了这些抗生素的作用。我们需要反击。直到最近，我们的进展一直受到阻碍，因为我们无法常规地合成制造这种聚合物的关键化学成分。我们现在可以做到这一点。这是令人兴奋的，因为我们发展了探索重要的悬而未决的问题的能力，这些问题是细菌如何生长和控制肽聚糖的生产的。我们希望将英国和加拿大科学家的专业知识聚集在一起，建立合作和协调的伙伴关系，以增加我们对这一过程的基础生物学的理解。所有这些都将从根本上开启新的生物学洞察力，并有机会将这些洞察力用于未来开发新的抗生素，这些抗生素将对MRSA和TB等多重耐药细菌起作用。

Millions of people die each year from bacterial infections and tens of millions suffer from the consequences of these infections. The discovery of the antibiotic penicillin once opened the door to treat these infections by stopping bacteria making the polymer in the cell wall that holds them together. This polymer, called peptidoglycan, is made up of an interlocking network of sugars and strings of amino acids (peptides). Specialised proteins (called PBPs), with the ability to stitch together these sugars and peptides are the targets inhibited by penicillin, stopping cell wall synthesis and killing the bacterium. Many important bacteria are no longer killed by penicillin and other antibiotics that attack other stages in the production of peptidoglycan. Bacteria have changed, evading the action of these antibiotics. We need to fight back. Our progress until recently has been hampered by our inability to routinely synthesise the key chemical components that make this polymer. We can now do this. This is exciting, as we develop the capability to explore important unanswered questions about how bacteria grow and control the production of peptidoglycan. We wish to pull together the expertise of UK and Canadian scientists in a cooperative and coordinated partnership to increase our understanding of the fundamental biology of this process. All of this will open fundamentally new biological insights, and opportunities to use these for the future development of new antibiotics that will work against multiply antibiotic resistant bacteria like MRSA and TB.