Tuzlak Leila, Pappas Téa E, Coyne Michael J, Sheahan Madeline L, Burgo Victoria, Rice Phoebe A, Comstock Laurie E
Duchossois Family Institute University of Chicago; Chicago, IL.
Department of Microbiology, University of Chicago; Chicago, IL.
bioRxiv. 2025 Aug 20:2025.08.20.671311. doi: 10.1101/2025.08.20.671311.
Antagonistic systems of bacteria are often tightly regulated. The human gut Bacteroidales harbor three distinct antagonistic Type VI secretion systems (T6SS), one of which is present only in , known as the GA3 T6SS. Although this is the best studied of the three T6SSs, little is known about how it is regulated. The gene upstream of the GA3 T6SS locus encodes a TetR family transcriptional regulator (TetR), which we show represses expression of the GA3 T6SS locus. The gene immediately upstream and divergently transcribed from , designated here as , encodes a product of the α-oxoamine synthase family of pyridoxal phosphate-dependent enzymes with structural homology to the CqsA autoinducer synthase of the CAI-1 quorum sensing system of . When is deleted, transcription of the GA3 T6SS locus is repressed in a TetR-dependent manner. Strains synthesizing Lgs produce a molecule present in the supernatant that likely serves as the TetR ligand, overcoming TetR transcriptional repression of the GA3 T6SS. We show that GA3 T6SS-specific immunity genes present on two acquired immunity defense islands are also regulated by Lgs coordinating expression of GA3 T6SS antagonism with protection from competitor's GA3 T6SS toxins. Production and firing of the GA3 T6SS and subsequent antagonism occurs in bacteria deleted for when grown with bacteria containing this gene or their supernatants. These data show that the GA3 T6SS is regulated by a small molecule acting through TetR allowing the bacteria to coordinate antagonistic and protective systems.
细菌的拮抗系统通常受到严格调控。人类肠道拟杆菌含有三种不同的拮抗型VI分泌系统（T6SS），其中一种仅存在于[具体名称未给出]中，称为GA3 T6SS。尽管这是三种T6SS中研究得最深入的一种，但对其调控方式知之甚少。GA3 T6SS基因座上游的基因编码一种TetR家族转录调节因子（TetR），我们发现它可抑制GA3 T6SS基因座的表达。紧邻GA3 T6SS基因座上游且转录方向相反的基因，在此处命名为[具体名称未给出]，编码一种磷酸吡哆醛依赖性酶的α-氧代胺合酶家族产物，其结构与[具体物种未给出]的CAI-1群体感应系统的CqsA自诱导合酶同源。当[具体名称未给出]缺失时，GA3 T6SS基因座的转录以TetR依赖的方式受到抑制。合成Lgs的菌株会产生一种存在于上清液中的分子，该分子可能作为TetR配体，克服TetR对GA3 T6SS的转录抑制。我们发现，存在于两个获得性免疫防御岛上的GA3 T6SS特异性免疫基因也受Lgs调控，从而协调GA3 T6SS的拮抗作用与对竞争者GA3 T6SS毒素的保护作用。当缺失[具体名称未给出]的细菌与含有该基因的细菌或其上清液一起培养时，GA3 T6SS的产生、发射及随后的拮抗作用就会发生。这些数据表明，GA3 T6SS受一种通过TetR起作用的小分子调控，使细菌能够协调拮抗和保护系统。
