RcsAB and Fur Coregulate the Iron-Acquisition System via entC in Klebsiella pneumoniae NTUH-K2044 in Response to Iron Availability

Yuan, Lingyue; Li, Xuan; Du, Ling; Su, Kewen; Zhang, Jiaxue; Pin, Liu; He, Qiang; Zhang, Zhongshuang; Peng, Dan; Shen, Lifei; Qiu, Jingfu; Li, Yingli

doi:10.3389/fcimb.2020.00282

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…Interestingly, the Rcs system is involved in production of colanic acid capsule, thus, an interrelation between O antigen polymerization in LPS and colanic acid in the stress response is plausible as denotes the fact that bacteria without O antigen in LPS overproduces colanic acid ( 64 ). Also, the relation between Rcs and regulation of iron related genes is observed in the RNAseq analysis upon expression of the RcsB M88A variant and it has been demonstrated in a recent publication that the heterocomplex RcsB-RcsA together with Fur co-regulate iron-acquisition via entC in Klebsiella pneumoniae ( 65 ). This previously unknown aspect of RcsB over iron regulation highlights the crucial role that iron plays in bacterial physiology in basal and altered conditions, not in vain, iron regulation is also under control of the stress response sigma factor RpoS (σ S ) to prevent oxidative stress ( 66 ).…”

Section: Discussionmentioning

confidence: 96%

Structure-based analyses ofSalmonellaRcsB variants unravel new features of the Rcs regulon

Huesa

Giner‐Lamia

Pucciarelli

et al. 2021

Nucleic Acids Research

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RcsB is a transcriptional regulator that controls expression of numerous genes in enteric bacteria. RcsB accomplishes this role alone or in combination with auxiliary transcriptional factors independently or dependently of phosphorylation. To understand the mechanisms by which RcsB regulates such large number of genes, we performed structural studies as well as in vitro and in vivo functional studies with different RcsB variants. Our structural data reveal that RcsB binds promoters of target genes such as rprA and flhDC in a dimeric active conformation. In this state, the RcsB homodimer docks the DNA-binding domains into the major groove of the DNA, facilitating an initial weak read-out of the target sequence. Interestingly, comparative structural analyses also show that DNA binding may stabilize an active conformation in unphosphorylated RcsB. Furthermore, RNAseq performed in strains expressing wild-type or several RcsB variants provided new insights into the contribution of phosphorylation to gene regulation and assign a potential role of RcsB in controlling iron metabolism. Finally, we delimited the RcsB box for homodimeric active binding to DNA as the sequence TN(G/A)GAN4TC(T/C)NA. This RcsB box was found in promoter, intergenic and intragenic regions, facilitating both increased or decreased gene transcription.

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Section: Discussionmentioning

confidence: 96%

Structure-based analyses ofSalmonellaRcsB variants unravel new features of the Rcs regulon

Huesa

Giner‐Lamia

Pucciarelli

et al. 2021

Nucleic Acids Research

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“…Furthermore, a total of 14 pathogenic genes with significant differences in abundance were identified between the two groups. Among them, entA,entC, entF, fepC, fepG, and iucA were the major virulence factors related to iron uptake in K. pneumoniae (Yuan et al, 2020); the pilus regulatory gene fimK promotes the virulence of K. pneumoniae in murine pneumonia (Rosen et al, 2015;Liu et al, 2022); arcB may mediate resistance against host-derived antimicrobial peptides (Padilla et al, 2010); magA is associated with the virulent hypermucoviscous K. pneumoniae strains (Cubero et al, 2016). The relationship between these genes and the invasiveness of KPLA should be verified via further research.…”

Section: Discussionmentioning

confidence: 98%

Metagenome Analysis of the Bacterial Characteristics in Invasive Klebsiella Pneumoniae Liver Abscesses

Zhang

Wang

Guo

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundKlebsiella pneumoniae liver abscess (KPLA) combined with extrahepatic migratory infection (EMI) is defined as invasive KPLA (IKPLA) and is associated with a poor prognosis. The mechanism of IKPLA formation is yet to be elucidated. In this study, metagenomic sequencing was used to compare the bacterial characteristics between IKPLA and KPLA to explore the underlying mechanism of invasiveness.MethodsClinical details, imaging, and microbial features were retrospectively evaluated by medical record review. Metagenomic sequencing was performed on the pus samples of liver abscesses whose culture results were indicative of monomicrobial Klebsiella pneumoniae (K. pneumoniae). Bacterial diversity and composition in IKPLA and KPLA were comparatively analyzed, and the key pathways and genes that may affect invasiveness were further explored.ResultsSixteen patients were included in this study. Five patients with EMI were included in the IKPLA group, and the other eleven patients without EMI were assigned to the KPLA group. There was no statistical difference in the hypermucoviscous phenotype and serotype of K. pneumoniae between the two groups. The bacterial diversity of IKPLA was lower than that of KPLA. The abundant taxa in the IKPLA group were primarily species of unclassified Enterobacteriaceae and K. pneumoniae. The KPLA group had a high abundance of the genera Tetrasphaera and Leuconostoc. Metabolic pathway genes represented most of the enriched genes in IKPLA. Fourteen pathogenic genes with significant differences in abundance were identified between the two groups, including ybtS, fepC, phoQ, acrB, fimK, magA, entC, arnT, iucA, fepG, oqxB, entA, tonB, and entF (p < 0.001).ConclusionThe diversity and bacterial composition of IKPLA were significantly different from those of KPLA. Microbiological changes in the abscess, activation of the related metabolic pathways, and the pathogenic gene expression may constitute a novel mechanism that regulates the invasiveness of KPLA.

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“…The result that biofilm formation on abiotic surfaces was reduced following knockdown of the ykgK gene suggested that the ykgk gene played a role in biofilm formation. In K. pneumoniae, it is known that Type 1 and 3 fimbriae play an important role in the formation of biofilms [7,37,38]. After studying the ykgK gene, it was found that the phenotypes were related to biofilm formation, in addition to Type 1 and Type 3 fimbriae, as well as ECP fimbriae.…”

Section: Infection Of G Mellonella Larvaementioning

confidence: 99%

“…Current research on the virulence of K. pneumoniae has also attracted much attention. The known virulence factors of K. pneumoniae mainly include capsular polysaccharide (CPS), lipopolysaccharide, fimbriae, urease, biofilm formation‐related factors, and the iron capture system [2–7]. Bacterial biofilms are surface‐related aggregates embedded in extracellular polymer intermediates, which help bacteria resist external environmental stimuli.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of ECP fimbriae‐related genes by the transcriptional regulator RcsAB in Klebsiella pneumoniae NTUH‐K2044

Shen

Zhang²,

Xue

et al. 2022

J Basic Microbiol

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Klebsiella pneumoniae is one of the major pathogens causing nosocomial infections.The regulator of capsule synthesis (Rcs) system is a complex signal transduction pathway that is involved in the regulation of virulence factors of K. pneumoniae as an important transcriptional regulator. The RcsAB box-like sequence was found to be present in the promoter-proximal regions of ykgK, one of the ECP fimbriaerelated genes, which suggested the expression of ECP fimbriae may be regulated by RcsAB. The ykgK gene in K. pneumoniae has 86% similarity to the ecpR gene in Escherichia coli. Nucleotide sequence alignment revealed a similar ECP fimbriae gene cluster including six genes in K. pneumoniae, which was proved to be on the same operon in this study. The electrophoretic mobility shift assay and DNase I assay, relative fluorescence expression, β-galactosidase activity, and relative gene expression of ykgK in the wild-type and mutant strains were performed to determine the transcriptional regulation mechanism of RcsAB on ECP fimbriae. The mutant ΔykgK and complementary strain ΔykgK/cΔykgK were constructed to complete the Galleria mellonella larvae infection experiment and biofilm formation assay. This study showed that RcsAB binds directly to the promoter region of the ykgK gene to positively regulate ECP fimbriae-related gene clusters, and then positively affect the biofilm formation. K E Y W O R D S ECP fimbriae-related gene, Klebsiella pneumoniae, RcsAB, transcriptional regulator, ykgK gene 1 | INTRODUCTION Klebsiella pneumoniae is a common opportunistic pathogen that can cause urinary and respiratory tract infections, pneumonia, bacteraemia, and sepsis [1]. Current research on the virulence of K. pneumoniae has also attracted much attention. The known virulence factors of K. pneumoniae mainly include capsular polysaccharide (CPS), lipopolysaccharide, fimbriae, urease, biofilm formation-related factors, and the iron capture

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RcsAB and Fur Coregulate the Iron-Acquisition System via entC in Klebsiella pneumoniae NTUH-K2044 in Response to Iron Availability

Cited by 11 publications

References 52 publications

Structure-based analyses ofSalmonellaRcsB variants unravel new features of the Rcs regulon

Structure-based analyses ofSalmonellaRcsB variants unravel new features of the Rcs regulon

Metagenome Analysis of the Bacterial Characteristics in Invasive Klebsiella Pneumoniae Liver Abscesses

Regulation of ECP fimbriae‐related genes by the transcriptional regulator RcsAB in Klebsiella pneumoniae NTUH‐K2044

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