SdiA Improves the Acid Tolerance of E. coli by Regulating GadW and GadY Expression

Abstract

The acid tolerance mechanism is important for Escherichia coli to resist acidic conditions encountered in mammalian host digestive tract environment. Here, we explored how the LuxR protein SdiA influenced E. coli acid tolerance ability in the context of the glutamateand glutamine-dependent acid resistance system (AR2). First, using a growth and acid shock assay under different acid stresses, we demonstrated that the deletion of sdiA in SM10λpir or BW25113 led to impaired growth under the acidic environment of pH 3-6, which was restored by complementary expression of SdiA. Next, transcriptome sequencing and qPCR disclosed that the expression of glutamate decarboxylase W (GadW) and GadY, the key members of the AR2 system, were regulated by SdiA. Further, β-galactosidase reporter assays showed that the promoter activity of gadW and gadY was positively regulated by SdiA. Moreover, qPCR and β-galactosidase reporter assays confirmed that the regulation of SdiA on GadW, but not GadY, could be enhanced by quorum sensing (QS) signal molecules AHLs. Collectively, these data suggest that SdiA plays a crucial role in acid tolerance regulation of E. coli. Our findings provide new insights into the important contribution of quorum sensing system AHLs-SdiA to the networks that regulate acid tolerance.

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

“…In many pathogens, the SdiA regulator modulates the expression of several virulence factors, such as adherence and motility ( Kanamaru et al, 2000 ; Sharma et al, 2010 ), multidrug resistance ( Tavio et al, 2010 ), biofilm formation ( Culler et al, 2018 ) and acid tolerance ( Ma et al, 2020 ). Concerning K. pneumoniae , little is known about the role of SdiA in the pathogenesis of this bacterium and, to date, no member of the SdiA regulon had been described in K. pneumoniae .…”

“…SdiA stands for “suppressor of cell division inhibition” and directly regulates gene expression by binding to regulatory elements, termed SdiA-box, located at the promoter region of the target genes ( Yamamoto et al, 2001 ). Reports indicate that the nucleotide sequence of the SdiA-box consists of the sequence AAAA (with minor variations) at both ends, intercalated with a spacer sequence that can vary from 8, 10, to 18 nucleotides ( Yamamoto et al, 2001 ; Shimada et al, 2014 ; Lu et al, 2017 ; Ma et al, 2020 ). SdiA regulates the transcription of the target genes by complexing with AHLs synthesized by other bacterial species ( Michael et al, 2001 ; Smith and Ahmer, 2003 ; Ahmer, 2004 ), in response to synthetic AHLs ( Shimada et al, 2014 ; Styles et al, 2020 ), or even in the absence of AHLs ( Yamamoto et al, 2001 ; Dyszel et al, 2010 ; Shimada et al, 2014 ; Nguyen et al, 2015 ).…”

“…Acting as a transcriptional regulator, SdiA has been implicated in the regulation of several cellular processes including cell division ( Sitnikov et al, 1996 ) and in the expression of virulence factors such as antibiotic resistance, motility and biofilm formation ( Kanamaru et al, 2000 ; Sharma et al, 2010 ; Antunes et al, 2010 ; Tavio et al, 2010 ; Culler et al, 2018 ; Ma et al, 2020 ). 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.…”

Regulation of Escherichia coli fim gene transcription by GadE and other acid tolerance gene products

“…Acid response system two is the glutamate decarboxylase system [20,21,27,28], which is positively regulated by the GadE protein [30,34,65,66]. Transcription of gadE is in turn activated by GadX and GadW [22,65,[67][68][69][70][71][72][73][74]. Even though the AR2 system mutants had the most obvious effects on fim gene transcription, the differences were all less than three-fold.…”

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

“…SdiA was identified as a "suppressor of cell division suppressors" that controls the transcription of ftsQAZ operons involved in cell division. It has been noted that in enterohemorrhagic Escherichia coli (EHEC) and Enterobacteriaceae, SdiA is involved in the regulation of many virulence factors, such as pili production, biofilm formation, adhesion and motility of cells (22)(23)(24). In addition,, Salmonella utilizes SdiA proteins to detect AHLs synthesized by other species and enhances srgE and RCK operon expression (20,11).…”