PecS regulates the urate-responsive expression of type 1 fimbriae in Klebsiella pneumoniae CG43

Abstract

In the Klebsiella pneumoniae CG43 genome, the divergently transcribed genes coding for PecS, the MarR-type transcription factor, and PecM, the drug metabolite transporter, are located between the type 1 and type 3 fimbrial gene clusters. The intergenic sequence pecO between pecS and pecM contains three putative PecS binding sites and a CpxR box. Electrophoretic mobility shift assay revealed that the recombinant PecS and CpxR could specifically bind to the pecO sequence, and the specific interaction of PecS and pecO could be attenuated by urate. The expression of pecS and pecM was negatively regulated by CpxAR and PecS, and was inducible by exogenous urate in the absence of cpxAR. Compared with CG43S3DcpxAR, the derived mutants CG43S3DcpxARDpecS and CG43S3DcpxARDpecSDpecM exerted similar levels of sensitivity to H 2 O 2 or paraquat, but higher levels of mannose-sensitive yeast agglutination activity and FimA production. The promoter activity and transcript levels of fimA in CG43S3DcpxAR were also increased by deleting pecS. However, no binding activity between PecS and the fimA promoter could be observed. Nevertheless, PecS deletion could reduce the expression of the global regulator HNS and release the negative effect of HNS on FimA expression. In CG43S3DcpxAR, the expression of FimA as well as PecS was inducible by urate, whilst urate-induced FimA expression was inhibited by the deletion of pecS. Taken together, we propose that K. pneumoniae PecS indirectly and negatively regulates the expression of type 1 fimbriae, and the regulation is urateinducible in the absence of CpxAR.

High Levels of Cyclic Di-GMP in Klebsiella pneumoniae Attenuate Virulence in the Lung

“…S1). These data indicate that while MrkH is the primary mediator of c-di-GMP signaling leading to Consistent with prior reports (32,33), decreased type 3 pilus production in TOP52 ΔmrkH was associated with increased type 1 piliation relative to that in wild-type K. pneumoniae. While the sizes of the fimS phase-on populations were appreciable in all TOP52 ΔmrkH transformants, the size of the phase-on population of TOP52 ΔmrkH/ pCMW75 was increased compared to that for the controls (Fig.…”

“…This work begins to illustrate the complexity of interactions between type 1 pili, type 3 pili, and c-di-GMP in K. pneumoniae. For example and as previously reported (33,34), the loss of type 3 pili results in increased type 1 pilus production through regulatory mechanisms that remain unclear. Furthermore, while c-di-GMP promotes increased expression of each adhesin, for type 3 pili, this is mediated by both MrkH-dependent and MrkH-independent effects, while type 1 pili exhibit only MrkH-independent regulation.…”

Identification of Two Regulators of Virulence That Are Conserved in Klebsiella pneumoniae Classical and Hypervirulent Strains

“…The contribution of the MarR family to the virulence of K. pneumoniae may be both strain and infection site dependent. Previously, the role of the MarR family protein, PecS, was shown to be important for repressing the type 1 fimbrial gene locus in K. pneumoniae strain CG43 ( 57 ). Type 1 fimbriae have been implicated in binding to mannose-containing structures and are important for causing UTI ( 58 ).…”

The KP1_4563 gene is regulated by the cAMP receptor protein and controls type 3 fimbrial function in Klebsiella pneumoniae NTUH-K2044

“…In this strain, the type 1 and type 3 fimbrial gene clusters are physically linked. The 4.6-kb DNA fragment between the gene clusters fim and mrk comprises five open reading frames (ORFs): KP1_4562 and KP1_4563 , which are two hypothetical protein encoding genes; KP1_4564 and KP1_4565 , which are pec M and pec S homologues, respectively; and KP1_4566 , which is a putative high affinity nickel transporter encoding gene [26, 27]. The function of KP1_456 3 is currently unknown, but the KP1_4563 protein has putative conserved domains of unknown function (DUF1471).…”