Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2)

Arakawa, Yoshichika; Ohta, Michio; Wacharotayankun, R; Mori, Masahiko; Kido, Nobuo; Ito, Hideo; Komatsu, Takayuki; Sugiyama, Tatsuo; Kato, Naoya

doi:10.1128/iai.59.6.2043-2050.1991

Cited by 52 publications

(28 citation statements)

References 39 publications

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“…1A). Two other Klebsiella mutants with cell surface defects, waaQ (Benghezal et al, 2006) and rmpA (Arakawa et al, 1991), gave similar results to wbbM (data not shown). The fact that wbbM, waaQ and rmpA Klebsiella mutants are non-virulent in mice (Benghezal et al, 2006) suggests that the Tetrahymena-Klebsiella assay provides a relevant measure of the virulence of K. pneumoniae towards mammals.…”

Section: Resultssupporting

confidence: 53%

Inhibitors of bacterial virulence identified in a surrogate host model

Benghezal¹,

Adam²,

Lucas³

et al. 2007

Cell Microbiol

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SummaryAntibiotic resistance continues to reduce the number of available antibiotics, increasing the need for novel antibacterial drugs. Since the seminal work of Sir Alexander Fleming, antibiotic identification has been based exclusively on the inhibition of bacterial growth in vitro. Recently, inhibitors of bacterial virulence which interfere with bacterial pathogenesis mechanisms have been proposed as an alternative to antibiotics, and a few were discovered using assays targeting specific virulence mechanisms. Here we designed a simple surrogate host model for the measurement of virulence and systematic discovery of anti-virulence molecules, based on the interaction of Tetrahymena pyriformis and Klebsiella pneumoniae cells. We screened a library of small molecules and identified several inhibitors of virulence. In a mouse pneumonia model we confirmed that an anti-virulence molecule displayed antibacterial activity against Klebsiella pneumoniae and Pseudomonas aeruginosa, by reducing dramatically the bacterial load in the lungs. This molecule did not inhibit bacterial growth in vitro but prevented biosynthesis of the Klebsiella capsule and lipopolysaccharides, a key requirement for virulence. Our results demonstrate that anti-virulence molecules represent an alternative to antibiotics and those can be discovered using nonanimal host models.

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Section: Resultssupporting

confidence: 53%

Inhibitors of bacterial virulence identified in a surrogate host model

Benghezal¹,

Adam²,

Lucas³

et al. 2007

Cell Microbiol

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“…The knowledge on the regulation of capsule formation is rather limited. It involves the products of rmpA and RcsA genes which also regulate the synthesis of polysaccharides in enterobacteria [10,11] and recently was reported to be in£uenced by environmental conditions [12]. In the present study, we sought to determine the relationship between the phenotypic expression of capsular material and type 1 ¢mbriae in K. pneumoniae.…”

Section: Introductionmentioning

confidence: 97%

Inability of encapsulated Klebsiella pneumoniae to assemble functional type 1 fimbriae on their surface

Matatov

1999

FEMS Microbiology Letters

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We screened phase variants of Klebsiella pneumoniae isolates for the expression of capsule and type 1 fimbriae and found that all of the 22 blood isolates were encapsulated and did not express type 1 fimbriae while 10 of 11 urinary tract isolates expressed type 1 fimbriae but were unencapsulated. Phase variants from selected isolates were found to be either unencapsulated and fimbriated or lacked both structures. Variants expressing both structures were not detected. Fimbrial subunits FimH and FimA were localized in the periplasmic space of the parent strain and on the surface of the unencapsulated variants. The results suggest that capsule formation impedes assembly of pre-formed fimbrial subunits on the bacterial surface. ß

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“…In vitro studies have shown that the capsule mediates protection against phagocytosis and the bactericidal e¡ect of serum [2^5]. By using animal models the capsule has been identi¢ed as a virulence factor when K. pneumoniae was inoculated into skin lesions [4,6], lungs [7,8] and intraperitoneally [7,9,10]. The role of capsule in serum poor compartments is less clari¢ed.…”

Section: Introductionmentioning

confidence: 99%

“…The genetic and biosynthetic pathways of capsule expression in K. pneumoniae are poorly characterized. Only the K2-serotype gene cluster has been cloned and the genomic organization determined [9,16]. However, only a few open reading frames have been assigned a function and only some parts of the cluster are conserved among di¡erent capsule serotypes [14,16].…”

Section: Introductionmentioning

confidence: 99%

Role of capsule in Klebsiella pneumoniae virulence: lack of correlation between in vitro and in vivo studies

Struve

2003

FEMS Microbiology Letters

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In vitro and in vivo models were used to investigate the role of capsule on the virulence of Klebsiella pneumoniae. We showed that capsule expression reduces dramatically the ability of the K. pneumoniae to bind to epithelial cells when compared to its non-capsulated variant. The presence/absence of capsule had no effect on the colonization of the gastrointestinal tract, while in the urinary tract we established that capsule is an important virulence factor. Our study demonstrates the caution needed when extrapolating from results of in vitro studies and emphasizes the necessity of in vivo models in studies of bacterial virulence.

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Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2)

Abstract: The genes determining the biosynthesis of type 2 (K2) capsular polysaccharide [ GIC4 Ma,n3(GlcUA) 1,4 1 ypio Gl-p a(~j-GcA * Corresponding author. Strain or plasmid Relevant genotypea Reference or source Strains K. pneumoniae Chedid Laboratory strain (01:K2)

Cited by 52 publications

References 39 publications

Inhibitors of bacterial virulence identified in a surrogate host model

Inhibitors of bacterial virulence identified in a surrogate host model

Inability of encapsulated Klebsiella pneumoniae to assemble functional type 1 fimbriae on their surface

Role of capsule in Klebsiella pneumoniae virulence: lack of correlation between in vitro and in vivo studies

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