SdiA, a Quorum-Sensing Regulator, Suppresses Fimbriae Expression, Biofilm Formation, and Quorum-Sensing Signaling Molecules Production in Klebsiella pneumoniae

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.

Klebsiella pneumoniae Biofilms and Their Role in Disease Pathogenesis

“…Besides FimK and KpfR, our group has recently described a quorum-sensing regulator, SdiA, which controls the expression of virulence factors, including type I fimbriae, and affects biofilm formation ( Pacheco et al., 2021 ). Mutant strains lacking SdiA showed increased biofilm formation in vitro , which correlates with an up-regulation of type 1 fimbriae, suggesting that SdiA acts as a repressor for fimbriae production and biofilm formation.…”

SdiA, a Quorum Sensing Transcriptional Regulator, Enhanced the Drug Resistance of Cronobacter sakazakii and Suppressed its Motility, Adhesion and Biofilm Formation

“…Pacheco et al also found that no significant changes were observed in the growth curves of Klebsiella pneumoniae SdiA mutant and wild-type strains. However, cell division was impaired, and cell morphology was abnormal (19). This is similar to the results found in this study.…”

“…In addition, a lack of SdiA can increase the formation of Klebsiella pneumoniae biofilms and agglutination of yeast cells and lead to downregulation of type 3 and upregulation of type 1 pili expression. More importantly, SdiA inhibits bacterial adhesion and biofilm aggregation (14, 19, 21).…”

“…The AI-1-type QS system is mainly responsible for communication between Gram-negative bacteria. LuxI and LuxR are two key proteins: LuxI synthase produces N-acyl homoserine lactones (AHLs) as its own inducers, and the LuxR transcription factor is their homologous receptor (15)(16)(17)(18)(19). The AI-2-type QS system is present in both Gram-negative and Gram-positive bacteria, and LuxS is a key protein (20,21).…”

“…Interestingly, some Gram-negative bacteria encode LuxR receptors but do not produce AHLs because they lack LuxI synthase. For instance, Klebsiella pneumoniae , Salmonella and Enterobacterium do not have the LuxI synthase gene, and they do not produce AHL signaling molecules (11, 19). However, there is a chromosomal LuxR homolog called SdiA of these bacteria; these bacteria can use the SdiA sensor to sense the signaling molecules produced by other bacteria in the environment and then regulate the expression of their own related genes (22).…”