The high-affinity phosphate transporter Pst is a virulence factor for<i>Proteus mirabilis</i>during complicated urinary tract infection

Jacobsen, S. M.; Lane, M. Chelsea; Harro, Jean M.; Shirtliff, Mark E.; Mobley, Harry L. T.

doi:10.1111/j.1574-695x.2007.00358.x

Cited by 38 publications

(45 citation statements)

References 55 publications

(72 reference statements)

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“…The AP encoded by phoA, a member of the Pho regulon, is widely used as an indicator to monitor the level of expression of the Pho regulon (8,17,20,26). Under high-phosphate conditions, the wild-type strain demonstrated a minimal baseline of AP production.…”

Section: Resultsmentioning

confidence: 99%

“…The Pho regulon is an important part of a complex network that encompasses not only phosphate homeostasis but also adaptive responses to stress and altered regulation of a diversity of genes, including virulence factors (5,10,20,26). In our study, we dissected the specific contributions of both the PhoBR two-component regulatory and Pst systems to virulence of an APEC O78 strain.…”

Section: Discussionmentioning

confidence: 99%

“…Coculture. Coculture was performed as described previously (6,20), with some modifications. Briefly, equal quantities (5 ϫ 10 6 CFU) of the QT51 ⌬lacZYA derivative of strain 7122 and either mutant strain were used from overnight LB cultures to initiate the coculture in 5 ml of fresh LB medium without antibiotics.…”

Section: Methodsmentioning

confidence: 99%

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Increased Pho Regulon Activation Correlates with Decreased Virulence of an Avian Pathogenic Escherichia coli O78 Strain

et al. 2010

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Avian pathogenic Escherichia coli (APEC) strains are associated with respiratory infections, septicemia, cellulitis, peritonitis, and other conditions, since colibacillosis manifests in many ways. The Pho regulon is jointly controlled by the two-component regulatory system PhoBR and by the phosphate-specific transport (Pst) system. To determine the specific roles of the PhoBR regulon and the Pst system in the pathogenesis of the APEC O78 strain 7122, different phoBR and pst mutant strains were tested in vivo in chickens and in vitro for virulence traits. Mutations resulting in constitutive activation of the Pho regulon rendered strains more sensitive than the wild type to hydrogen peroxide and to the bactericidal effects of rabbit serum. In addition, production of type 1 fimbriae was also impaired in these strains. Using a chicken competitive infection model, all PhoB constitutive mutants were outcompeted by the wild-type parent, including strains containing a functional Pst system. Cumulative inactivation of the Pst system and the PhoB regulator resulted in a restoration of virulence. In addition, loss of the PhoB regulator alone did not affect virulence in the chicken infection model. Interestingly, the level of attenuation of the mutant strains correlated directly with the level of activation of the Pho regulon. Overall, results indicate that activation of the Pho regulon rather than phosphate transport by the Pst system plays a major role in the attenuation of the APEC O78 strain 7122.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Increased Pho Regulon Activation Correlates with Decreased Virulence of an Avian Pathogenic Escherichia coli O78 Strain

et al. 2010

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“…pst mutants are highly attenuated in cochallenge colonization of the CBA mouse model (Burall et al, 2004;Jacobsen et al, 2008). P. mirabilis HI4320 possesses a pst operon identical in gene organization to that observed in Escherichia coli.…”

Section: Introductionmentioning

confidence: 99%

The high-affinity phosphate transporter Pst in Proteus mirabilis HI4320 and its importance in biofilm formation

et al. 2009

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Proteus mirabilis causes urinary tract infections (UTIs) in individuals requiring long-term indwelling catheterization. The pathogenesis of this uropathogen is mediated by a number of virulence factors and the formation of crystalline biofilms. In addition, micro-organisms have evolved complex systems for the acquisition of nutrients, including the phosphate-specific transport system, which has been shown to be important in biofilm formation and pathogenesis. A functional Pst system is important during UTIs caused by P. mirabilis HI4320, since transposon mutants in the PstS periplasmic binding protein and the PstA permease protein were attenuated in the CBA mouse model of UTI. These mutants displayed a defect in biofilm formation when grown in human urine. This study focuses on a comparison of the proteomes during biofilm and planktonic growth in phosphate-rich medium and human urine, and microscopic investigations of biofilms formed by the pst mutants. Our data suggest that (i) the Dpst mutants, and particularly the DpstS mutant, are defective in biofilm formation, and (ii) the proteomes of these mutants differ significantly from that of the wild-type. Therefore, since the Pst system of P. mirabilis HI4320 negatively regulates biofilm formation, this system is important for the pathogenesis of these organisms during complicated UTIs. INTRODUCTIONProteus mirabilis -a member of the family Enterobacteriaceae -is the most common aetiological agent responsible for complicated urinary tract infections (UTIs) (Mobley, 1996). Subpopulations at higher risk for infection by this pathogen include those with long-term indwelling catheterization as well as those with structural and functional abnormalities within the urinary tract (Mobley, 1996). Clinical syndromes associated with P. mirabilis include cystitis and pyelonephritis, with possible complications from stone formation and bacteraemia (Mobley, 1996). These micro-organisms survive in the urinary tract by virtue of their production of a battery of virulence factors, including urease, flagella, fimbriae, haemolysin and IgA protease (Belas, 1996;Mobley et al., 1994;Musher et al., 1975;Peerbooms et al., 1984; Walker et al., 1999), and formation of crystalline biofilm on indwelling catheters (Stickler et al., 1993).Biofilm formation -one of the most important mechanisms of pathogenicity of this micro-organism in the urinary tract -may be defined as a community of surface-attached bacteria encased in an extracellular matrix consisting of secreted carbohydrates, proteins and DNA. Indeed, biofilms have been associated with the virulence of a number of pathogens (Castelli et al., 2006). Organisms in these communities display phenotypic differences from planktonic cells, including a slower rate of growth and increased resistance to antibiotics (Lewis, 2001;Stoodley et al., 2002). P. mirabilis biofilms in urine are unique in that the extracellular polysaccharide matrix is enmeshed with struvite and carbonate apatite crystals (Jones et al., 2006).Abbreviations: CLSM, confocal ...

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“…These infections typically occur in patients with functional or anatomical abnormalities of the urinary tract or patients subjected to long-term catheterization (such as those with spinal cord injuries or elderly patients residing in nursing homes). The serious sequelae (including catheter encrustation, stone formation, renal scarring, and potential for progression to bacteremia) that can result from these P. mirabilis infections (46,70,71), as well as the difficulty in treating them, have sparked active research into the mechanisms of pathogenesis (2,13,19,27,28,65,78) and the identification of potential vaccine candidates (1, 40-42, 47, 56, 61). One of the most notable characteristics of P. mirabilis is swarming motility, a specialized form of flagellum-mediated motility during which bacteria differentiate into elongated hyperflagellated cells; these differentiated cells migrate together en masse (57).…”

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confidence: 99%

Zinc Uptake Contributes to Motility and Provides a Competitive Advantage to Proteus mirabilis during Experimental Urinary Tract Infection

2010

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Proteus mirabilis, a Gram-negative bacterium, represents a common cause of complicated urinary tract infections in catheterized patients or those with functional or anatomical abnormalities of the urinary tract. ZnuB, the membrane component of the high-affinity zinc (Zn 2؉ ) transport system ZnuACB, was previously shown to be recognized by sera from infected mice. Since this system has been shown to contribute to virulence in other pathogens, its role in Proteus mirabilis was investigated by constructing a strain with an insertionally interrupted copy of znuC. The znuC::Kan mutant was more sensitive to zinc limitation than the wild type, was outcompeted by the wild type in minimal medium, displayed reduced swimming and swarming motility, and produced less flaA transcript and flagellin protein. The production of flagellin and swarming motility were restored by complementation with znuCB in trans. Swarming motility was also restored by the addition of Zn 2؉ to the agar prior to inoculation; the addition of Fe 2؉to the agar also partially restored the swarming motility of the znuC::Kan strain, but the addition of Co 2؉ , Cu 2؉ , or Ni 2؉ did not. ZnuC contributes to but is not required for virulence in the urinary tract; the znuC::Kan strain was outcompeted by the wild type during a cochallenge experiment but was able to colonize mice to levels similar to the wild-type level during independent challenge. Since we demonstrated a role for ZnuC in zinc transport, we hypothesize that there is limited zinc present in the urinary tract and P. mirabilis must scavenge this ion to colonize and persist in the host.

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The high-affinity phosphate transporter Pst is a virulence factor forProteus mirabilisduring complicated urinary tract infection

Cited by 38 publications

References 55 publications

Increased Pho Regulon Activation Correlates with Decreased Virulence of an Avian Pathogenic Escherichia coli O78 Strain

Increased Pho Regulon Activation Correlates with Decreased Virulence of an Avian Pathogenic Escherichia coli O78 Strain

The high-affinity phosphate transporter Pst in Proteus mirabilis HI4320 and its importance in biofilm formation

Zinc Uptake Contributes to Motility and Provides a Competitive Advantage to Proteus mirabilis during Experimental Urinary Tract Infection

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