Tettmann Beatrix, Niewerth Christine, Kirschhöfer Frank, Neidig Anke, Dötsch Andreas, Brenner-Weiss Gerald, Fetzner Susanne, Overhage Joerg
Karlsruhe Institute of Technology, Institute of Functional Interfaces Karlsruhe, Germany.
Institute for Molecular Microbiology and Biotechnology, University of Münster Münster, Germany.
Front Microbiol. 2016 Dec 9;7:1978. doi: 10.3389/fmicb.2016.01978. eCollection 2016.
The 2-alkyl-3-hydroxy-4(1)-quinolone 2,4-dioxygenase HodC was previously described to cleave the quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS) system of , an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of attenuated production of virulence factors, and reduced virulence . However, proteolytic cleavage reduced the efficacy of HodC. Here, we identified the secreted protease LasB of to be responsible for HodC degradation. In static biofilms of the PA14 ::Tn mutant, the catalytic activity of HodC led to an increase in viable biomass in newly formed but also in established biofilms, and reduced the expression of genes involved in iron metabolism and siderophore production, such as , and . This is likely due to an increase in the levels of bioavailable iron by degradation of PQS, which is able to sequester iron from the surrounding environment. Thus, HodC, despite its ability to quench the production of virulence factors, is contraindicated for combating biofilms.
2-烷基-3-羟基-4(1)-喹诺酮2,4-双加氧酶HodC先前被描述为可切割喹诺酮信号PQS，PQS专门用于铜绿假单胞菌复杂的群体感应（QS）系统，铜绿假单胞菌是一种利用QS调节毒力和生物膜形成的机会致病菌。通过向铜绿假单胞菌浮游细胞外源性添加HodC来降解PQS，可减弱毒力因子的产生，并降低毒力。然而，蛋白水解切割降低了HodC的功效。在此，我们确定铜绿假单胞菌分泌的蛋白酶LasB是导致HodC降解的原因。在铜绿假单胞菌PA14::Tn突变体的静态生物膜中，HodC的催化活性导致新形成的生物膜以及已形成的生物膜中活生物质增加，并降低了参与铁代谢和铁载体产生的基因的表达，如pvdS、pqsA和pqsR。这可能是由于PQS降解导致生物可利用铁水平增加，PQS能够从周围环境中螯合铁。因此，尽管HodC有能力抑制毒力因子的产生，但它并不适合用于对抗铜绿假单胞菌生物膜。
