Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, PO Box 3640, Karlsruhe, 76021, Germany.
BMC Microbiol. 2013 Apr 9;13:77. doi: 10.1186/1471-2180-13-77.
Pseudomonas aeruginosa is an important opportunistic human pathogen and is extremely difficult to treat due to its high intrinsic and adaptive antibiotic resistance, ability to form biofilms in chronic infections and broad arsenal of virulence factors, which are finely regulated. TypA is a GTPase that has recently been identified to modulate virulence in enteric Gram-negative pathogens.
Here, we demonstrate that mutation of typA in P. aeruginosa resulted in reduced virulence in phagocytic amoebae and human macrophage models of infection. In addition, the typA mutant was attenuated in rapid cell attachment to surfaces and biofilm formation, and exhibited reduced antibiotic resistance to ß-lactam, tetracycline and antimicrobial peptide antibiotics. Quantitative RT-PCR revealed the down-regulation, in a typA mutant, of important virulence-related genes such as those involved in regulation and assembly of the Type III secretion system, consistent with the observed phenotypes and role in virulence of P. aeruginosa.
These data suggest that TypA is a newly identified modulator of pathogenesis in P. aeruginosa and is involved in multiple virulence-related characteristics.
铜绿假单胞菌是一种重要的机会性人类病原体，由于其固有和适应性抗生素耐药性高、在慢性感染中形成生物膜的能力以及精细调节的广泛毒力因子，因此极难治疗。TypA 是一种 GTPase，最近被发现可调节肠道革兰氏阴性病原体的毒力。
在这里，我们证明了铜绿假单胞菌中 typA 的突变导致吞噬性变形虫和人类巨噬细胞感染模型中的毒力降低。此外，TypA 突变体在快速细胞附着到表面和生物膜形成方面减弱，并且对β-内酰胺、四环素和抗菌肽抗生素的耐药性降低。定量 RT-PCR 显示，在 TypA 突变体中，与 III 型分泌系统的调节和组装有关的重要毒力相关基因下调，与观察到的表型和铜绿假单胞菌的毒力作用一致。
这些数据表明，TypA 是铜绿假单胞菌发病机制的新发现调节剂，涉及多种与毒力相关的特征。
