Broendum Sebastian S, Williams Daniel E, Hayes Brooke K, Kraus Felix, Fodor James, Clifton Ben E, Geert Volbeda Anne, Codee Jeroen D C, Riley Blake T, Drinkwater Nyssa, Farrow Kylie A, Tsyganov Kirill, Heselpoth Ryan D, Nelson Daniel C, Jackson Colin J, Buckle Ashley M, McGowan Sheena
Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia.
Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
Mol Microbiol. 2021 Aug;116(2):397-415. doi: 10.1111/mmi.14719. Epub 2021 Apr 3.
Endolysin enzymes from bacteriophage cause bacterial lysis by degrading the peptidoglycan cell wall. The streptococcal C1 phage endolysin PlyC, is the most potent endolysin described to date and can rapidly lyse group A, C, and E streptococci. PlyC is known to bind the Group A streptococcal cell wall, but the specific molecular target or the binding site within PlyC remain uncharacterized. Here we report for the first time, that the polyrhamnose backbone of the Group A streptococcal cell wall is the binding target of PlyC. We have also characterized the putative rhamnose binding groove of PlyC and found four key residues that were critical to either the folding or the cell wall binding action of PlyC. Based on our results, we suggest that the interaction between PlyC and the cell wall may not be a high-affinity interaction as previously proposed, but rather a high avidity one, allowing for PlyC's remarkable lytic activity. Resistance to our current antibiotics is reaching crisis levels and there is an urgent need to develop the antibacterial agents with new modes of action. A detailed understanding of this potent endolysin may facilitate future developments of PlyC as a tool against the rise of antibiotic resistance.
来自噬菌体的内溶素酶通过降解肽聚糖细胞壁引起细菌裂解。链球菌C1噬菌体的内溶素PlyC是迄今为止所描述的最有效的内溶素，它能迅速裂解A、C和E组链球菌。已知PlyC能结合A组链球菌细胞壁，但PlyC内的特定分子靶点或结合位点仍未明确。在此，我们首次报道A组链球菌细胞壁的聚鼠李糖主链是PlyC的结合靶点。我们还对PlyC假定的鼠李糖结合凹槽进行了表征，发现了四个对PlyC的折叠或细胞壁结合作用至关重要的关键残基。基于我们的研究结果，我们认为PlyC与细胞壁之间的相互作用可能并非如先前提出的那样是一种高亲和力相互作用，而是一种高亲合力相互作用，这使得PlyC具有显著的裂解活性。对当前抗生素的耐药性正达到危机水平，迫切需要开发具有新作用模式的抗菌剂。对这种强效内溶素的详细了解可能会促进PlyC作为一种对抗抗生素耐药性上升的工具的未来发展。
