Clostridium perfringens strains cause a wide variety of human and animal disease, including gas gangrene or myonecrosis. Production of toxins required for myonecrosis, PFO and CPA, is regulated by the C. perfringens Agr-like (CpAL) system via the VirSR two-component system. Myonecrosis begins at the site of infection from where bacteria migrate deep into the host tissue likely using a previously described gliding motility phenotype. We therefore assessed whether gliding motility was under the control of the CpAL/VirSR regulon. The migration rate of myonecrosis-causing C. perfringens strain 13 (S13) was investigated during a 96 h period, including an adaptation phase with bacterial migration (∼1.4 mm/day) followed by a gliding phase allowing bacteria faster migration (∼8.6 mm/day). Gliding required both an intact CpAL system, and signaling through VirSR. Mutants lacking ΔagrB, or ΔvirR, were impaired for onward gliding while a complemented strain S13ΔagrB/pTS1303 had the gliding phenotype restored. Gene expression studies revealed upregulated transcription of pili genes (pilA1, pilA2 and pilT) whose encoded proteins were previously found to be required for gliding motility and CpAL/VirSR-regulated pfoA and cpa toxin genes. Compared to S13, transcription of cpa and pfoA significantly decreased in S13ΔagrB, or S13ΔvirR, strains but not that of pili genes. Further experiments demonstrated that mutants S13ΔpfoA and S13Δcpa migrated at the same rate as S13 wt. We demonstrated that CpAL/VirSR regulates C. perfringens gliding motility and that gliding bacteria have an increased transcription of toxin genes involved in myonecrosis.

产气荚膜梭菌菌株引起多种人类和动物疾病，包括气性坏疽或肌坏死。肌坏死所需的毒素、PFO 和 CPA 的产生由产气荚膜梭菌Agr 样 (CpAL) 系统通过 VirSR 双组分系统进行调节。肌坏死开始于感染部位，从那里细菌可能使用先前描述的滑动运动表型迁移到宿主组织深处。因此，我们评估了滑翔运动是否受 CpAL/VirSR 调节子的控制。引起肌坏死的产气荚膜梭菌的迁移率在 96 小时内对菌株 13（S13）进行了研究，包括适应阶段，细菌迁移（~1.4 毫米/天），然后是允许细菌更快迁移的滑动阶段（~8.6 毫米/天）。滑翔既需要完整的 CpAL 系统，也需要通过 VirSR 发出信号。缺乏 Δ agrB或 Δ virR 的突变体在向前滑动时受损，而补充菌株 S13Δ agrB / pTS1303 的滑动表型恢复。基因表达研究揭示了 pili 基因（pilA1、pilA2和pilT）的转录上调，其编码的蛋白质以前被发现是滑翔运动和 CpAL/VirSR 调节的pfoA和cpa 所必需的毒素基因。与 S13 相比，cpa和pfoA 的转录在 S13Δ agrB或 S13Δ virR菌株中显着降低，但在菌毛基因中没有。进一步的实验表明，突变体 S13Δ pfoA和 S13Δ cpa以与 S13 wt 相同的速率迁移。我们证明 CpAL/VirSR 调节产气荚膜梭菌的滑行运动，并且滑行细菌具有增加的参与肌坏死的毒素基因的转录。