Regulation of the H1 Type VI Secretion System by the Transcriptional Regulator NfxB in Pseudomonas aeruginosa

The type VI secretion system (T6SS) is a widely distributed molecular apparatus found in most Gram-negative bacteria. Studies show that T6SSs have functions in bacterial virulence, inter- and intra-bacterial competition, and environmental adaptation. <i>Pseudomonas aeruginosa</i>, an opportunistic pathogen, harbors three T6SS gene clusters that perform diverse roles in clinical infection. Herein, using DNA affinity chromatography of the H1-T6SS promoter, the fluoroquinolone antibiotic resistance regulator NfxB was identified. Further studies demonstrated that NfxB negatively regulates the expression of H1-T6SS by directly binding to its promoter region. T6SS expression and effector secretion are regulated by the fluoroquinolone antibiotic via NfxB, which enhances inter-bacterial competition in the complex bacterial ecology. Meanwhile, the deletion of <i>nfxB</i> alters carbenicillin resistance through an unknown pathway. This study provides new insights into the regulation of T6SS by environmental signals, and it provides data support for antibiotic resistance and inter-bacterial competition due to T6SSs.