Mirabilis Urinary Tract Infection Research Articles

Substances Secreted by Lactobacillus spp. from the Urinary Tract Microbiota Play a Protective Role against Proteus mirabilis Infections and Their Complications.

Proteus mirabilis urinary tract infections can lead to serious complications such as development of urinary stones. Lactobacillus spp., belonging to the natural microbiota of the urinary tract, exhibit a number of antagonistic mechanisms against uropathogens, including the secretion of organic acids. In this study, we determined the anti-adhesion, anti-cytotoxicity and anti-crystallization properties of the substances secreted by Lactobacillus. For this purpose, membrane inserts with a pore diameter 0.4 μm were used, which prevent mixing of cultured cells, simultaneously enabling the diffusion of metabolic products. The intensity of crystallization was assessed by measuring the levels of Ca2+, Mg2+ and NH3 and by observing crystals using microscopic methods. The cytotoxicity of the HCV-29 cell line was determined using the LDH and MTT assays, and the impact of lactobacilli on P. mirabilis adhesion to the bladder epithelium was assessed by establishing CFU/mL after cell lysis. It was shown that in the presence of L. gasseri the adhesion of P. mirabilis and the cytotoxicity of the cells decreased. The degree of crystallization was also inhibited in all experimental models. Moreover, it was demonstrated that L. gasseri is characterized by the secretion of a high concentration of L-lactic acid. These results indicate that L-lactic acid secreted by L. gasseri has a significant impact on the crystallization process and pathogenicity of P. mirabilis.

The molybdate-binding protein ModA is required for Proteus mirabilis-induced UTI.

Proteus mirabilis is one of the pathogens commonly causing urinary tract infections (UTIs). The molybdate-binding protein ModA encoded by modA binds molybdate with high affinity and transports it. Increasing evidence shows that ModA promotes the survival of bacteria in anaerobic environments and participates in bacterial virulence by obtaining molybdenum. However, the role of ModA in the pathogenesis of P. mirabilis remains unknown. In this study, a series of phenotypic assays and transcriptomic analyses were used to study the role of ModA in the UTIs induced by P. mirabilis. Our data showed that ModA absorbed molybdate with high affinity and incorporated it into molybdopterin, thus affecting the anaerobic growth of P. mirabilis. Loss of ModA enhanced bacterial swarming and swimming and up-regulated the expression of multiple genes in flagellar assembly pathway. The loss of ModA also resulted in decreased biofilm formation under anaerobic growth conditions. The modA mutant significantly inhibited bacterial adhesion and invasion to urinary tract epithelial cells and down-regulated the expression of multiple genes associated with pilus assembly. Those alterations were not due to anaerobic growth defects. In addition, the decreased bacteria in the bladder tissue, the weakened inflammatory damage, the low level of IL-6, and minor weight change was observed in the UTI mouse model infected with modA mutant. Here, we reported that in P. mirabilis, ModA mediated the transport of molybdate, thereby affecting the activity of nitrate reductase and thus affecting the growth of bacteria under anaerobic conditions. Overall, this study clarified the indirect role of ModA in the anaerobic growth, motility, biofilm formation, and pathogenicity of P. mirabilis and its possible pathway, and emphasized the importance of the molybdate-binding protein ModA to P. mirabilis in mediating molybdate uptake, allowing the bacterium to adapt to complex environmental conditions and cause UTIs. Our results provided valuable information on the pathogenesis of ModA-induced P. mirabilis UTIs and may facilitate the development of new treatment strategies.

La calcolosi delle vie urinarie in età pediatrica a tutto tondo

Overall, the incidence of paediatric urolithiasis is increasing; 50-90% of cases are due to metabolic alterations, 3-30% are associated with urinary tract infections and the remaining cases are idio-pathic. About 20-30% of children, especially boys who are younger than 2 years of age, present an anatomic urinary tract anomaly. The main symptom is abdominal pain; however, young children tend to have subtle manifestations. Abdominal ultrasound is the first-line imaging technique. Conservative treatment with fluid intake, pain relievers and alpha-adrenergic blockers are used during the acute episode, whereas a surgical treatment is indicated in selected cases. Since there is an increased rate of recurrence in comparison to adulthood, abundant hydration and changes in dietary habits have a central role in the prevention of paediatric urolithiasis. It is very important to perform a metabolic evaluation when the acute episode is resolved, as 50% of the cases present an underlying metabolic disorder. If a metabolic abnormality is diagnosed, specific preventive interventions should be undertaken. The paper presents the clinical case of an infant who during a Proteus mirabilis urinary tract infection has developed obstructive acute kidney injury due to a stone in the distal urethra. The incidence of urinary stones caused by urinary tract infection is decreasing, however this eventuality should be considered.

Investigation of IL-6, IL-8 and TNF-α among patients infected with Proteus mirabilis in UTI Cases

Aims: In human Urinary Tract Infection (UTI) consider one of the most common bacterial infections, the purpose of this research was to assess the association between Interleukin-6 (IL-6), Interleukin-8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α) level in P. mirabilis UTI cases. Methodology: 160 samples of urine and blood were gotten from persons Suffer UTI, their age reached to (10-60) years, in addition to 100 samples of urine and blood from Healthy persons as a control group. All urine samples were inoculated by sterile loop immediately on blood agar plate and MacConkey agar plate and incubated aerobically at 37°C for 24 hr. Colony Forming Units (CFUs) method was used for growing single and pure bacterial colonies for target bacteria. Enzyme-Linked Immunosorbent Assay (ELISA) kit was used for detection level of human cytokines (IL-6, IL-8 and TNF-α) in inpatient and control groups. Results: The result showed that 62.5% of samples were positive for P. mirabilis. The level of IL-6, IL-8 and TNF-α considerably were high inpatient which reached to (312.189±0.916, 272.417±8.699 and 93.908±0.912)respectively, compared with control group (75.416±0.721, 77.978±0.932 and 51.777±0.556) respectively. There were important connotations between age, gender and placement and P. mirabilis infection. Conclusion: Target cytokines piece a critical role in UTI especially in acute phase. Also, there were substantial variances in age group, gender, and residency regarding infected with P. mirabilis and there are important relationships between IL-6, IL-8 and TNF-α in the patients infected with P. mirabilis.

A novel multi-peptide subunit vaccine admixed with AddaVax adjuvant produces significant immunogenicity and protection against Proteus mirabilis urinary tract infection in mice model

Proteus mirabilis is a common pathogen in urinary tract infections (UTIs). There is no vaccine against P. mirabilis, thus a novel multi-peptide vaccine of MrpA, UcaA and Pta factors of P. mirabilis we designed and a mice model was used to evaluate its efficacy in combination with AddaVax adjuvant. According to the bioinformatics studies, 7 fragments of MrpA (31–75, 112–146), UcaA (68–117, 132–156) and Pta (210–265, 340–400, 496–570) with B and T cell epitope regions were selected for fusion construction. Mice subcutaneously vaccinated with the fusion MrpA.Pta.UcaA induced a significant increase in serum and mucosal IgG and IgA responses. The fusion also showed a significant induction in cellular responses (Th1 and Th2). The addition of AddaVax to fusion and the mixture of MrpA, UcaA, and Pta (MUP) improved the humoral and cellular responses, especially the IgG2a and IFN-γ (Th1 responses) levels. Fusion with and without AddaVax and MUP + AddaVax could maintain significant humoral responses until 6 months after the first vaccine dose. All vaccine combinations with and without adjuvant showed high effectiveness in the protection of the bladder and kidney against experimental UTI; this could be attributed to the significant humoral and cellular responses. The present study suggests that the AddaVax-based vaccine formulations especially the fusion Pta.MrpA.UcaA admixed with AddaVax as potential vaccine candidates for protection against P. mirabilis. Furthermore, AddaVax could be considered as an effective adjuvant in designing other vaccines against UTI pathogens.

Construction and evaluation of the immune protection of a recombinant divalent protein composed of the MrpA from MR/P fimbriae and flagellin of Proteus mirabilis strain against urinary tract infection

Urinary tract infections (UTI) caused by Proteus mirabilis are prevalent among the catheterized patients. There is no effective vaccine to reduce the frequency of UTIs caused by P. mirabilis. In the present study, the immune responses and effectiveness of different combinations of MrpA and flagellin (FliC) of P. mirabilis were assessed intranasally in the mice model. The addition of FliC as adjuvant to MrpA in fusion form significantly raised the mucosal IgA and cellular (IFN-γ and IL-17) responses and maintained the serum IgG responses for 180 days after the first vaccination. Furthermore, MrpA in fusion form with FliC significantly increased the systemic, mucosal and IFN-γ responses of the FliC alone. In a bladder challenge assay with P. mirabilis, the fusion MrpA.FliC and the mixture of MrpA and FliC significantly decreased the colony count of the bacteria in the bladder and kidneys of mice in comparison to the control mice. It suggests a complex of the systemic, mucosal and cellular responses are needed for protection of the bladder and kidneys against P. mirabilis UTI. In our knowledge, the adjuvant property of the recombinant P. mirabilis flagellin was evaluated for the first time in a vaccine combination administered by an intranasal route. Our results suggest the recombinant flagellin of P. mirabilis could be used as an intranasal adjuvant in combination with other potential antigens against UTIs.

Inhibition of Urease Enzyme Production and some Other Virulence Factors Expression in Proteus mirabilis by N-Acetyl Cysteine and Dipropyl Disulphide.

In this study we evaluated the effect of N-acetyl cysteine (NAC) and dipropyl disulphide on some virulence factors expressed by a Proteus mirabilis strain isolated from a catheterized patient. Antibacterial activity of both compounds was determined by broth microdilution method. Their effect on different types of motility was determined by LB medium with variable agar content and sub-MIC of each drug. Their effect on adherence and mature biofilms was tested by tissue culture plate assay. Inhibitory effect on urease production was determined and supported by molecular docking studies. The minimum inhibitory concentration (MIC) of NAC and dipropyl disulphide was 25 mM and 100 mM, respectively. Both compounds decreased the swarming ability and biofilm formation of the tested isolate in a dose-dependent manner. NAC had higher urease inhibitory activity (IC50 249 ±0.05 mM) than that shown by dipropyl disulphide (IC50 10±0.2 mM). Results were supported by molecular docking studies which showed that NAC and dipropyl disulphide interacted with urease enzyme with binding free energy of -4.8 and -8.528 kcal/mol, respectively. Docking studies showed that both compounds interacted with Ni ion and several amino acids (His-138, Gly-279, Cysteine-321, Met-366 and His-322) which are essential for the enzyme activity. NAC and dipropyl disulphide could be used in the control of P. mirabilis urinary tract infections.

Vaccines in prophylaxis of urinary tract infections caused by the bacteria from the genus Proteus.

Urinary tract infections (UTIs) pose a threat especially to women, the individuals with weakened immunity or with abnormalities in the urinary tract as well as to hospitalized and catheterized patients. The bacteria from the genus Proteus, especially P. mirabilis, are important UTI pathogenic factors. They frequently cause chronic, recurrent or severely complicated infections, resulting in the urinary stones production due to urease and other virulence factors. The ability to survive inside the stones and the increasing antibiotic resistance make it difficult to eradicate the bacteria from the urinary tract. A good solution to the problem may be the vaccination which obtained the interest from the surveyed persons, in spite of the antivaccination attitudes visible also in Poland. Currently, there are four vaccines available, composed of killed cells of different uropathogens, including Proteus spp. They are administrated intranassaly or vaginally and require many booster doses. They decrease the probability of reinfection in patients suffering from recurrent UTIs but the mechanisms of the immune response have not been exactly defined. Promising results were obtained in the studies on a mice model concerning the subunit, conjugated vaccines in which various P. mirabilis surface antigens (with the exception of flagellin) were successfully employed. Hitherto, the best results were obtained by the intranasal vaccinations, using MR/P fimbriae antigens with MPL or cholera toxin adjuvants and the antigens expressed in Lactococcus lactis or Salmonella Typhimurium. It led to an increase in the levels of the specific serum and mucosal antibodies resulting in the protection against P. mirabilis UTIs.

Proteus mirabilis flagellin, neither a good adjuvant nor a protective antigen against urinary tract infection

Event Abstract Back to Event Proteus mirabilis flagellin, neither a good adjuvant nor a protective antigen against urinary tract infection Paola Scavone1*, Ana Umpiérrez1, Analía Rial2, José A. Chabalgoity2 and Pablo Zunino1 1 Instituto de Investigaciones Biológicas Clemente Estable, Department of Microbiology, Uruguay 2 Instituto de Higiene, Department of Biotecnology, Uruguay P. mirabilis, a gram negative bacterium associated with complicated urinary tract infections (UTI), expresses several virulence factors including MR/P fimbriae and flagella. Flagellin from certain bacteria has shown interesting adjuvant and protective properties but P. mirabilis flagellin has not been analyzed so far. Here, we evaluated the role of P. mirabilis flagellin as protective antigen in a mouse UTI model, and its adjuvant capacity for the protective antigen MrpA (MR/P fimbriae structural subunit). Four groups of mice were intranasally immunised at days 0, 3, 10, 17 and 24 with either MrpA, flagellin, both proteins and PBS only. Before and after immunisation urine and blood samples were collected to evaluate antibodies induction. Cytokine production was analysed on day 30 in splenocytes. At day 31 mice were challenged using an ascending P. mirabilis UTI model, being sacrificed 7 days after for bacteria quantification in kidneys and bladders. MrpA-immunised mice showed a significant increase in serum and urine specific IgG and IgA while mice immunised with MrpA-flagellin or flagellin did not. Animals did not show significant anti-flagellin antibodies induction. MrpA-immunised showed a significant decrease in bacteria recovered from bladders and kidneys compared with any other group of mice. Instead, infection levels in flagellin, MrpA-flagellin and PBS-immunised mice showed no significant differences between them. Remarkably, IL-10 was significantly induced in the mice receiving flagellin or MrpA-flagellin. These results showed that P. mirabilis flagellin is not a good adjuvant and did not protect mice against UTI, and suggested that it may have an immunomodulatory role. Keywords: Flagellin, Urinary Tract Infections, adjuvants, Vaccines, MrpA antigen Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Scavone P, Umpiérrez A, Rial A, Chabalgoity JA and Zunino P (2013). Proteus mirabilis flagellin, neither a good adjuvant nor a protective antigen against urinary tract infection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00445 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Paola Scavone, Instituto de Investigaciones Biológicas Clemente Estable, Department of Microbiology, Montevideo, Montevideo, 11600, Uruguay, pscavone@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Paola Scavone Ana Umpiérrez Analía Rial José A Chabalgoity Pablo Zunino Google Paola Scavone Ana Umpiérrez Analía Rial José A Chabalgoity Pablo Zunino Google Scholar Paola Scavone Ana Umpiérrez Analía Rial José A Chabalgoity Pablo Zunino PubMed Paola Scavone Ana Umpiérrez Analía Rial José A Chabalgoity Pablo Zunino Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Proteus mirabilis urinary tract infection and bacteremia: Risk factors, clinical presentation, and outcomes

Proteus mirabilis is a common pathogen responsible for complicated urinary tract infections (UTIs) that sometimes causes bacteremia. Most cases of P. mirabilis bacteremia originate from a UTI; however, the risk factors for bacteremia and mortality rates from P. mirabilis UTI have not been determined. A retrospective, case-control study was performed between May 2008 and November 2010 to identify the risk factors and markers for P. mirabilis bacteremic UTI. Each subject in the case group (all patients were diagnosed with P. mirabilis bacteremia from a urinary tract source) was matched by age and gender to two subjects in the control group (patients diagnosed with P. mirabilis UTI but with negative blood culture results). Clinical presentation and laboratory data were analyzed to determine the risk factors and markers of P. mirabilis bacteremic UTI. Sixty-seven bacteremic UTIs and 124 nonbacteremic UTIs were included in this study. Community-acquired infection (p=0.017), hydronephrosis (p=0.017), band neutrophils accounting for >10% of the white blood cell count (p=0.001), hyperthermia or hypothermia (p=0.047), and a serum C-reactive protein concentration >100mg/L (p=0.002) were identified as independent risk factors for P. mirabilis bacteremic UTI. Seventeen patients died in hospital, including 11 in the bacteremic group and 6 in the nonbacteremic group. The bacteremic group had a higher mortality rate (p=0.016). Bacteremic UTI (p=0.049), shock (p=0.014), and a low body mass index (BMI) <18 kg/m(2) (p=0.033) were identified as independent risk factors for mortality. Because bacteremic P. mirabilis UTIs are associated with higher mortality, clinicians should carefully manage cases that present with the risk factors for bacteremia, including community-acquired infection, hydronephrosis, band neutrophils accounting for >10% of the white blood cell count, hyperthermia or hypothermia, and a high level of C-reactive protein.

Serotyping of Proteus mirabilis clinical strains based on lipopolysaccharide O-polysaccharide and core oligosaccharide structures

The aim of this work was to serotype Proteus mirabilis urinary tract infection (UTI) strains based on chemically defined O-antigens with the use of two clinical collections from Sweden and Poland consisting of 99 and 24 UTI strains, respectively. A simple two-step serotyping scheme was proposed using enzyme immunoassay with heat-stable surface antigens of Proteus cells and immunoblotting with isolated lipopolysaccharides (LPSs). Using polyclonal anti-P. mirabilis rabbit antisera, 50 Swedish and 8 Polish strains were classified into serogroups O10, O38, O36, O30, O17, O23, O9, O40, O49, O27, O5, O13, O24, O14, and O33. From the Swedish strains, 10 belonged to serogroup O10 and five to each of serogroups O38, O36, and O9. Therefore, none of the O-serogroups was predominant. The majority of the serotyped clinical strains possess acidic O-antigens containing uronic acids and various acidic non-carbohydrate substituents. In immunoblotting, antisera cross-reacted with both O-antigen and core of LPSs. The core region of 19 LPSs bound a single serum, and that of 12 LPSs bound more than two sera. Following bioinformatic analysis of the available sequences, a molecular approach to the prediction of Proteus core oligosaccharide structures was proposed. The identification of the core type of P. mirabilis R110, derived from a serogroup O3 wild strain, using restriction fragments length polymorphism analysis of galacturonic acid transferase is shown as an example. In summary, the most frequent O-serogroups among P. mirabilis UTI stains were identified. The diversity of serological reactions of LPSs is useful for serotyping of P. mirabilis clinical isolates. A possible role of the acidic components of O-antigens in UTI is discussed.

Nasal immunization with attenuated Salmonella Typhimurium expressing an MrpA–TetC fusion protein significantly reduces Proteus mirabilis colonization in the mouse urinary tract

The development of effective strategies to prevent urinary tract infections (UTIs) has become an important goal in public health. Proteus mirabilis is commonly associated with complicated UTIs and expresses several virulence factors, including mannose-resistant Proteus-like (MR/P) fimbriae. Here, a fusion protein formed from MrpA, the structural protein of MR/P fimbriae, and TetC, a non-toxic but highly immunogenic fragment of tetanus toxin, to be delivered by an attenuated Salmonella Typhimurium mutant in vivo was constructed. The ability of this strain to induce an immune response and to protect mice against a urinary tract challenge with P. mirabilis was investigated. The protein was successfully expressed in S. Typhimurium. After two immunization doses, intra-nasally vaccinated mice showed a significant increase in specific serum IgG against MrpA and against Salmonella lipopolysaccharide, as well as a significant decrease in kidney and bladder colonization by P. mirabilis after challenge. However, no significant correlation was observed between antibody response and kidney or bladder colonization. MrpA fused to TetC and expressed in S. Typhimurium effectively protected mice against an experimental P. mirabilis UTI.

Assessment of effectiveness and safety of Ibicella lutea extract in the control of experimental Proteus mirabilis urinary tract infection

Proteus mirabilis is an important cause of complicated urinary tract infections (UTI). Like many other microorganisms, P. mirabilis has acquired resistance to many antibiotics. Due to the serious effects associated with uropathogenic P. mirabilis and the problems related to the use of antibiotics, alternative strategies for its control must be developed. Previously, we studied the effect of Ibicella lutea extract, a South American indigenous plant, on in vitro uropathogenicity of P. mirabilis. We observed that I. lutea extract had an effect on various attributes associated with P. mirabilis urovirulence. The objective of this study was to assess I. lutea extract against UTI by P. mirabilis. This study was based on the effect of I. lutea extract to prevent or treat P. mirabilis experimental UTI in mice and the influence of this administration on the normal intestinal flora. Also, we studied the toxicity, mutagenicity, and antimutagenicity of the extract. In this study, while I. lutea administration showed an effect in the prevention and treatment of UTI in the mouse, the intestinal microflora did not change. The I. lutea extract was neither toxic nor mutagenic although the extract showed antimutagenic properties. These findings suggest that the administration of I. lutea extract could represent an interesting new strategy to control P. mirabilis UTI.

Effect of Ibicella lutea on uropathogenic Proteus mirabilis growth, virulence, and biofilm formation

Proteus mirabilis, an important uropathogen that can cause complicated urinary tract infections (UTI), has emerged as a therapeutic problem following mutations that compromise the use of antimicrobial drugs. Due to the serious effects associated with uropathogenic P. mirabilis and the problems related to the use of antibiotics, it is necessary to develop alternative strategies for its control. The objective of this study was to assess the effect of Ibicella lutea extract, a South American indigenous plant, on growth, virulence and biofilm production of uropathogenic P. mirabilis. This study was based on the extract generation and the assessment of its effect on bacterial features related to virulence. These assays involved determination of antibacterial activity, swarming motility, Western blot to assess expression of fimbriae and flagella, biofilms formation, haemagglutination, haemolysis, and electron microscopy. I. lutea extract had an effect on bacterial growth rate and bacterial morphology. It also affected P. mirabilis swarming differentiation, hemagglutination and biofilm formation on glass and polystyrene. These findings suggest that I. lutea may have a role as an agent for the control of P. mirabilis UTI.

Purple urine bag syndrome

A 58-year-old man with an indwelling urinary catheter began producing urine with a deep purple colour ([Figure 1][1]). The urine was alkaline (pH 7.8), and Proteus mirabilis urinary tract infection was diagnosed. This so-called purple urine bag syndrome resolved after treatment with ceftazidime. The

Henoch-Schönlein purpura associated with Proteus mirabilis urinary tract infection

Henoch-Schönlein purpura associated with Proteus mirabilis urinary tract infection

Mannose-resistantProteus-like andP. mirabilisfimbriae have specific and additive roles inP. mirabilisurinary tract infections

Proteus mirabilis is an important uropathogen that can cause complicated urinary tract infections (UTI). It produces several types of fimbriae, including mannose-resistant Proteus-like (MR/P) fimbriae and P. mirabilis fimbriae (PMF). Previously, we determined that these fimbriae affect the ability of P. mirabilis to colonize the urinary tract. The objective of this study was to analyse the effect of the simultaneous lack of P. mirabilis MR/P and PMF fimbriae in UTI pathogenesis. A double mutant lacking both fimbriae was generated by allelic replacement mutagenesis. This mutant was characterized genetically and phenotypically, and tested using an in vitro uroepithelial cell adhesion assay and the ascending UTI murine model. In vitro adhesion to uroepithelial cells by the P. mirabilis pmfA/mrpA-D mutant was reduced when compared with the wild-type, although no significant differences were observed when it was compared with the single mrpA-D and pmfA mutants. However, in vivo assays showed that colonization of kidneys and bladders by the P. mirabilis pmfA/mrpA-D mutant was significantly reduced when compared with the wild-type and both single mutants. These results indicate that, although redundancy can occur, MR/P and PMF fimbriae have specific and additive roles in P. mirabilis UTI.

Preventive and therapeutic administration of an indigenous Lactobacillus sp. strain against Proteus mirabilis ascending urinary tract infection in a mouse model

Probiotics are increasingly being considered as non-pharmaceutical and safe potential alternatives for the treatment and prevention of a variety of pathologies including urinary tract infections. These are the most common infections in medical practice and are frequently treated with antibiotics, which have generated an intense selective pressure over bacterial populations. Proteus mirabilis is a common cause of urinary tract infections in catheterised patients and people with abnormalities of the urinary tract. In this work we isolated, identified and characterised an indigenous Lactobacillus murinus strain (LbO2) from the vaginal tract of a female mouse. In vitro characterisation of LbO2 included acid and bile salts tolerance, growth in urine, adherence to uroepithelial cells and in vitro antimicrobial activity. The selected strain showed interesting properties, suitable for its use as a probiotic. The ability of LbO2 to prevent and even treat ascending P. mirabilis urinary tract infection was assessed using an experimental model in the mouse. Kidney and bladder P. mirabilis counts were significantly lower in mice preventively treated with the probiotic than in non-treated mice. When LbO2 was used for therapeutic treatment, bladder counts of treated mice were significantly lower although no significant differences were detected in P. mirabilis kidney colonisation of treated and non-treated animals. These results are encouraging and prompt further research related to probiotic strains and the basis of their effects for their use in human and animal health.

Mucosal vaccination of mice with recombinant Proteus mirabilis structural fimbrial proteins

Proteus mirabilis, a common cause of urinary tract infection (UTI), expresses several types of fimbria including mannose-resistant/ Proteus-like fimbriae (MRP), uroepithelial cell adhesin (UCA), renamed non-agglutinating fimbriae (NAF) by some authors, and P. mirabilis fimbriae (PMF), which are potentially involved in adhesion to the uroepithelium. In this study, we immunised different groups of mice with recombinant structural subunits of these fimbriae (MrpA, UcaA and PmfA) using two mucosal routes (nasal and transurethral) and we transurethrally challenged the animals with a P. mirabilis uropathogenic isolate. Induction of specific serum and urine IgG and IgA was measured to assess the potential role of the humoral immune response in protection against experimental ascending P. mirabilis UTI. Intranasally MrpA- and UcaA-immunised mice were protected against P. mirabilis ascending UTI, since recovery of bacteria from kidneys and bladders was significantly lower than in PBS-treated mice, and both fimbrial subunits significantly induced specific serum and urine antibodies. Only MrpA and PmfA transurethrally immunised animals were protected only at the kidney level, and in this case only MrpA-immunised mice exhibited significant serum IgG induction. Correlation analysis did not show a significant relationship between serum and urine specific antibody response and protection observed against infection. Our results suggest that an immunisation strategy based on structural fimbrial proteins may be useful to prevent P. mirabilis UTI. Further studies are being carried out to characterise the immune and inflammatory response induced by P. mirabilis recombinant fimbrial subunits.

Evaluation of Proteus mirabilis structural fimbrial proteins as antigens against urinary tract infections

Proteus mirabilis is a common cause of urinary tract infection (UTI) and produce several types of different fimbriae, including mannose-resistant/ Proteus-like fimbriae, uroepithelial cell adhesin (UCA), and P. mirabilis fimbriae (PMF). Different authors have related these fimbriae with different aspects of P. mirabilis pathogenesis, although the precise role of fimbriae in UTI has not yet been elucidated. In this work we expressed and purified recombinant structural fimbrial proteins of these fimbriae (MrpA, UcaA, and PmfA) and assessed their role as protective antigens using an ascending and a haematogenous model of UTI in the mouse. MrpA protected subcutaneously immunised mice in both models, suggesting that it could be taken into account as a promising vaccine candidate against P. mirabilis UTI. UcaA could also be an interesting subunit to be studied although it only protected mice that were challenged intravenously. All subunits elicited a strong specific serum IgG response but there was no significant correlation between antibody levels and protection. Only PmfA-immunised mice elicited a significant urinary antibody response but this protein was unable to confer protection against P. mirabilis experimental challenges. These results may contribute to the development of vaccines against P. mirabilis, an important cause of complicated UTI.