Pn-AqpC-Mediated Fermentation Pattern Coordination with the Two-Component System 07 Regulates Host N-Glycan Degradation of Streptococcus pneumoniae

• Published in: Microbiology spectrum 2022-10, Vol.10 (5), p.e0249622-e0249622
• Main Authors: Shen, Kaiqiang, Hu, Qingqing, Zhu, Lin, Miu, Wenshuang, Dong, Yuzhu, Ren, Fu, Dong, Xiuzhu, Tong, Huichun
• Format: Article
• Language: English
• Subjects: Antioxidants - metabolism; Aquaglyceroporins - metabolism; Aspartic Acid - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Fermentation; Fetuins - metabolism; formate; Formates - metabolism; Glucose - metabolism; Histidine Kinase - metabolism; homolactic acid fermentation; Humans; Lyases - metabolism; N-glycan degradation; Oxygen - metabolism; oxygen facilitator Pn-AqpC; Polysaccharides; Pyruvates - metabolism; Research Article; Streptococcus pneumoniae; Streptococcus pneumoniae - metabolism; two-component system 07
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.02496-22

The opportunistic pathogen Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal commensal, and host N-glycan metabolism promotes its colonization and invasion. It has been reported that glucose represses, while fetuin, a glycoconjugated model protein, induces, the genes involved in N-glycan degradation through the two-component system TCS07. However, the mechanisms of glucose repression and TCS07 induction remain unknown. Previously, we found that the pneumococcal aquaglyceroporin Pn-AqpC facilitates oxygen uptake, thereby contributing to the antioxidant potential and virulence. In this study, through Tandem Mass Tag (TMT) quantitative proteomics, we found that the deletion of Pn- caused a marked upregulation of 11 proteins involved in N-glycan degradation in glucose-grown pneumococcus R6. Both quantitative RT-PCR and GFP fluorescence reporters revealed that the upregulation of N-glycan genes was completely dependent on response regulator (RR) 07, but not on the histidine kinase HK07 of TCS07 or the phosphoryl-receiving aspartate residue of RR07 in ΔPn- , indicating that RR07 was activated in an HK07-independent manner when Pn-AqpC was absent. The deletion of Pn- also enhanced the expression of pyruvate formate lyase and increased formate production, probably due to reduced cellular oxygen content, indicating that a shunt of glucose catabolism to mixed acid fermentation occurs. Notably, formate induced the N-glycan degradation genes in glucose-grown R6, but the deletion of abolished this induction, indicating that formate activates RR07. However, the induction of N-glycan degradation proteins reduced the intraspecies competition of R6 in glucose. Therefore, although N-glycan degradation promotes pneumococcal pathogenesis, the glucose metabolites-based RR07 regulation reported here is of importance for balancing growth fitness and the pathogenicity of pneumococcus. Pneumococcus, a human opportunistic pathogen, is capable of metabolizing host complex N-glycans. N-glycan degradation promotes pneumococcus colonization in the nasopharynx as well as invasion into deeper tissues, thus significantly contributing to pathogenesis. It is known that the two-component system 07 induces the N-glycan metabolizing genes; however, how TCS07 is activated remains unknown. This study reveals that formate, the anaerobic fermentation metabolite of pneumococcus, is a novel activator of the response regulator (RR) 07. Although the high expression of N-glycan degradat