School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Department of Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Front Cell Infect Microbiol. 2024 Feb 7;14:1297818. doi: 10.3389/fcimb.2024.1297818. eCollection 2024.
The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen . However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.
The importance of three representative T6SS core genes involved in the drug resistance and virulence of , namely, , (), and was elucidated.
A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 clinical isolates. Upon deletion of in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The Δ mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The -lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the Δ mutant. Moreover, the Δ strain, followed by the Δ mutant, showed decreased survival in human serum, with attenuated competition with and impaired lethality in .
The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of , especially in terms of intrinsic resistance. Meanwhile, and contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.
型分泌系统(T6SS)是医院病原体的重要毒力因子。然而,其与耐药性的关系知之甚少。值得注意的是,不同 T6SS 成分在抗菌药物耐药过程中以及在毒力中的作用尚未得到系统揭示。
阐明了与 的耐药性和毒力相关的三个有代表性的 T6SS 核心基因 ()、 ()和 的重要性。
在我们的 114 株临床分离株中,耐药株中这三个核心基因的比例高于敏感株。在 AB795639 中缺失 后,观察到对头孢呋辛和头孢曲松的抗菌药物耐药性增加,同时对庆大霉素的耐药性降低。Δ 突变株对环丙沙星、诺氟沙星、氧氟沙星、四环素和强力霉素的耐药性降低,但对妥布霉素和链霉素的耐药性增加。- 缺失突变株对氧氟沙星、多粘菌素 B 和呋喃唑酮的敏感性增加。此外,仅在 Δ 突变株中观察到生物膜形成显著减少。此外,Δ 菌株随后是 Δ 突变株,在人血清中的存活率降低,与 和 的竞争能力降低,在 中的致死能力受损。
上述结果表明,T6SS 发挥重要作用,参与 的抗生素耐药性,特别是固有耐药性。同时, 和 对细菌毒力的贡献更大,tssM 更为重要。