Lactobacillus (L.) helveticus is widely used in food industry due to its high proteolytic activity. However, such activity varies greatly between isolates, and the determining factors regulating the strength of proteolytic activity in L. helveticus are unclear. This study sequenced the genomes of 60 fermented food-originated L. helveticus and systemically examined the proteolytic activity-determining factors. Our analyses found that the strength of proteolytic activity in L. helveticus was independent of the isolation source, geographic location, phylogenetic closeness between isolates, and distribution of cell envelope proteinases (CEPs). Genome-wide association study (GWAS) identified two genes, the acetate kinase (ackA) and a hypothetical protein, and 15 single nucleotide polymorphisms (SNPs) that were associated with the strength of the proteolytic activity. Further investigating the functions of these gene components revealed that ackA and two cysteine peptidases coding genes (pepC and srtA) rather than the highly heterogeneous and intraspecific CEPs were linked to the level of proteolytic activity. Moreover, the sequence type (ST) defined by SNP analysis revealed a total of ten STs, and significantly weaker proteolytic activity was observed among isolates of ST2. This study provides practical information for future selection of L. helveticus of strong proteolytic activity.

乳杆菌（L.）瑞士广泛，由于其较高的蛋白水解活性用于食品工业。但是，这种活性在分离株之间变化很大，并且尚不清楚调节瑞士乳杆菌中蛋白水解活性强度的决定因素。这项研究对60种发酵食品来源的瑞士乳杆菌的基因组进行了测序，并系统地研究了蛋白水解活性的决定因素。我们的分析发现，瑞士乳杆菌的蛋白水解活性强与分离源，地理位置，分离株之间的系统发育亲密性以及细胞被膜蛋白酶（CEP）的分布无关。全基因组关联研究（GWAS）鉴定了两个基因，即乙酸激酶（ack A）和一种假定蛋白，以及15种与蛋白水解活性有关的单核苷酸多态性（SNP）。进一步研究这些基因成分的功能后发现，ack A和两个半胱氨酸肽酶编码基因（pep C和srtA）而不是高度异质性和种内CEP与蛋白水解活性水平相关。此外，通过SNP分析确定的序列类型（ST）揭示总共十个ST，并且在ST2的分离株中观察到明显弱的蛋白水解活性。该研究为将来选择具有较强蛋白水解活性的瑞士乳杆菌提供了实用信息。