Wu Yanping, Hu Qiaoyun, Dehinwal Ruchika, Rakov Alexey V, Grams Nicholas, Clemens Erin C, Hofmann Jennifer, Okeke Iruka N, Schifferli Dieter M
Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China.
Microorganisms. 2020 Mar 30;8(4):489. doi: 10.3390/microorganisms8040489.
While advances in genomic sequencing have highlighted significant strain variability between and within serovars, only a few protein variants have been directly related to evolutionary adaptation for survival, such as host specificity or differential virulence. The current study investigated whether allelic variation of the adhesin/invasin PagN influences bacterial interaction with their receptors. The serovar Typhi ( Typhi) allelic variant of PagN was found to bind significantly better to different enterocytes as well as to the extracellular matrix protein laminin than did the major serovar Typhimurium ( Typhimurium) allele. The two alleles differed at amino acid residues 49 and 109 in two of the four predicted PagN surface loops, and residue substitution analysis revealed that a glutamic acid at residue 49 increased the adhesive and invasive properties of Typhi PagN. PagN sequence comparisons from 542 strains for six representative serovars and further supported the role of glutamic acid at residues 49 and 109 in optimizing adhesion to cells and laminin, as well as for cell invasion. In summary, this study characterized unique residues in allelic variants of a virulence factor that participates in the colonization and invasive properties of different stains, subspecies and serovars.
虽然基因组测序的进展突出了不同血清型之间以及血清型内部显著的菌株变异性，但只有少数蛋白质变体与生存的进化适应性直接相关，例如宿主特异性或不同的毒力。本研究调查了粘附素/侵袭素PagN的等位基因变异是否影响细菌与其受体的相互作用。结果发现，与主要的鼠伤寒血清型（Typhimurium）等位基因相比，伤寒血清型（Typhi）PagN的等位基因变体与不同肠上皮细胞以及细胞外基质蛋白层粘连蛋白的结合能力明显更强。这两个等位基因在四个预测的PagN表面环中的两个环的第49和109位氨基酸残基处存在差异，残基替代分析表明，第49位残基处的谷氨酸增加了伤寒血清型PagN的粘附和侵袭特性。对六个代表性血清型的542株菌株的PagN序列比较进一步支持了第49和109位残基处的谷氨酸在优化对细胞和层粘连蛋白的粘附以及细胞侵袭方面的作用。总之，本研究鉴定了一种毒力因子等位基因变体中的独特残基，该毒力因子参与了不同菌株、亚种和血清型的定植和侵袭特性。
