Abstract
Klebsiella pneumoniae is a Gram-negative pathogen that has become a worldwide concern due to the emergence of multidrug-resistant isolates responsible for various invasive infectious diseases. Biofilm formation constitutes a major virulence factor for K. pneumoniae and relies on the expression of fimbrial adhesins and aggregation of bacterial cells on biotic or abiotic surfaces in a coordinated manner. During biofilm aggregation, bacterial cells communicate with each other through inter- or intra-species interactions mediated by signallng molecules, called autoinducers, in a mechanism known as quorum sensing (QS). In most Gram-negative bacteria, intra-species communication typically involves the LuxI/LuxR system: LuxI synthase produces N-acyl homoserine lactones (AHLs) as autoinducers and the LuxR transcription factor is their cognate receptor. However, K. pneumoniae does not produce AHL but encodes SdiA, an orphan LuxR-type receptor that responds to exogenous AHL molecules produced by other bacterial species. While SdiA regulates several cellular processes and the expression of virulence factors in many pathogens, the role of this regulator in K. pneumoniae remains unknown. In this study, we describe the characterization of sdiA mutant strain of K. pneumoniae. The sdiA mutant strain has increased biofilm formation, which correlates with the increased expression of type 1 fimbriae, thus revealing a repressive role of SdiA in fimbriae expression and bacterial cell adherence and aggregation. On the other hand, SdiA acts as a transcriptional activator of cell division machinery assembly in the septum, since cells lacking SdiA regulator exhibited a filamentary shape rather than the typical rod shape. We also show that K. pneumoniae cells lacking SdiA regulator present constant production of QS autoinducers at maximum levels, suggesting a putative role for SdiA in the regulation of AI-2 production. Taken together, our results demonstrate that SdiA regulates cell division and the expression of virulence factors such as fimbriae expression, biofilm formation, and production of QS autoinducers in K. pneumoniae.
Highlights
Klebsiella pneumoniae is a Gram-negative bacterium responsible for various diseases that has become a worldwide concern due to the increase in cases of severe infections in the community (Keynan and Rubinstein, 2007; Lin et al, 2010; Holt et al, 2015)
Bacterial cell division relies on the ftsQAZ operon, which encodes the FtsQ, FtsA, and FtsZ proteins responsible for recruiting and assembling cell division machinery in the septum
We investigated the presence of putative SdiA binding sites within the promoter region of genes responsible for the synthesis of type 1 fimbriae, bacterial cell division, and the metabolism of type 2 autoinducers
Summary
Klebsiella pneumoniae is a Gram-negative bacterium responsible for various diseases that has become a worldwide concern due to the increase in cases of severe infections in the community (Keynan and Rubinstein, 2007; Lin et al, 2010; Holt et al, 2015). Much of K. pneumoniae pathogenicity comes from its ability to form biofilms (Li et al, 2014; Paczosa and Mecsas, 2016), which are microbial communities that grow attached to surfaces and typically surrounded by a matrix of self-produced extracellular polymeric substances (HallStoodley et al, 2004). The bacterial cells communicate with each other through inter- or intra-species interactions mediated by a mechanism called quorum sensing (QS). By this process, bacteria produce and detect specific signaling molecules to coordinate gene expression according to the bacterial cell density (Bassler et al, 1993; Miller and Bassler, 2001). Signaling is mediated by chemical molecules, known as autoinducers (AI), that determine two main types of cell-cell communication: AI-1 and AI-2 QS regulatory systems
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