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PubMed2002

A novel ophthalmic presentation of the Proteus syndrome.

PURPOSE: To report a patient with the Proteus syndrome who had ocular complications not previously described in the literature. DESIGN: Single observational case report. METHODS: Retrospective review of the medical record and review of the literature. RESULTS: The 26-year-old man has systemic features fulfilling the diagnostic criteria for the Proteus syndrome. His ocular abnormalities are myopia, mild calcific band keratopathy, cataract, abnormal vitreous structure, vitreous hemorrhage, a large chorioretinal mass, and a resolved serous retinal detachment. CONCLUSIONS: Ocular complications are frequently reported in patients with the Proteus syndrome. Few of the patients reported in the literature have had comprehensive ocular examination by an ophthalmologist. Our patient is unique because he has been examined by ophthalmologists from childhood, and it is clear that the ocular findings may change with time. As far as we are aware, calcific band keratopathy, abnormal vitreous structure, and chorioretinal hamartoma associated with serous retinal detachment and vitreous hemorrhage have not previously been described.

Adult↗
PubMed1993

Ophthalmologic examination in the diagnosis of Proteus syndrome.

PURPOSE: To describe the clinical features of Proteus syndrome, a rare recently recognized hamartoneoplastic malformation, with emphasis on the ocular findings. METHODS: Complete physical and ocular examination of two new patients with Proteus syndrome. RESULTS: The two reported cases illustrate the wide clinical polymorphism of Proteus syndrome and the overlap of its clinical manifestations with those of other overgrowth syndromes. Both patients had periorbital exostoses and epibulbar tumors. The ocular findings are compared with those in the literature. CONCLUSION: Considering the paucity of information in the ophthalmic literature, this article explores the role of the ophthalmologist in diagnosing this rare entity.

Abnormalities, Multiple↗
PubMed2002

New structures of the O-specific polysaccharides of bacteria of the genus Proteus. 1. Phosphate-containing polysaccharides.

The O-specific polysaccharide chains (O-antigens) of the lipopolysaccharides of five Proteus strains, P. vulgaris O17, P. mirabilis O16 and O33, and P. penneri 31and 103, were found to contain phosphate groups that link the non sugar components, e.g., ethanolamine and ribitol. The polysaccharides of P. mirabilis O16 and P. penneri 103 include ribitol phosphate in the main chain and thus resemble ribitol teichoic acids of Gram-positive bacteria. The structures of the polysaccharides were elucidated using NMR spectroscopy, including two-dimensional 1H,1H correlation spectroscopy (COSY and TOCSY), nuclear Overhauser effect spectroscopy (NOESY or ROESY), and H-detected 1H,13C and 1H,31P heteronuclear multiple-quantum coherence spectroscopy (HMQC), along with chemical methods. The structures determined are unique among the bacterial polysaccharides and, together with the data obtained earlier, represent the chemical basic for classification of Proteus strains. Based on structural similarities of the O-specific polysaccharides and serological relationships between the O-antigens, we propose to extend Proteus serogroups O17 and O19 by including P. penneri strains 16 and 31,respectively.

Carbohydrate Conformation↗
PubMed1997

A motile but non-swarming mutant of Proteus mirabilis lacks FlgN, a facilitator of flagella filament assembly.

A TnphoA mutant of Proteus mirabilis was isolated, which had lost the ability to swarm, yet was still motile. The transposon had inserted into flgN, a flagella gene encoding a 147-amino-acid protein of undefined function. Proteus flgN is arranged in an operon with the class III anti-sigma28 gene, flgM, flanked by the class II genes, flgA, flgBCD and flhBA, and a novel putative virulence-related gene. The flgN mutation caused a substantial reduction in cell surface-associated flagellin, particularly during differentiation to the normally hyperflagellated swarm cell. This was not due to an effect on flagella gene expression or a typical defect in the flagella export apparatus as there was no class III gene downregulation by FlgM feedback, or intracellular flagellin accumulation. Loss of FlgN nevertheless caused a severe reduction in the incorporation of pulse-labelled flagellin into the membrane/flagellum fraction of differentiating cells. Substantial amounts of both non-oligomeric flagellin and flagellin degradation products appeared in the extracellular medium, although the few mature filaments made by the mutant were no more sensitive to proteolysis than those of the wild type. FlgN appeared soluble and active in the cytosol. The data suggest that the function of FlgN is to facilitate the initiation of flagella filament assembly, a role that may be especially critical in attaining the much higher concentration of surface flagellin required for swarming. Proteus FlgN has leucine zipper-like motifs arranged on potential amphipathic helices, a feature conserved in cytosolic chaperones for the exported substrates of flagella-related type III virulence systems. While gel filtration of FlgN from the soluble cell fraction did not establish an interaction with flagellin, it indicated that FlgN may associate with an unknown component and/or form an oligomer.

Amino Acid Sequence↗
PubMed1998

Structural and serological studies on a new acidic O-specific polysaccharide of Proteus vulgaris O32.

The following structure of the O-specific polysaccharide chain (O-antigen) of the Proteus vulgaris 032 lipopolysaccharide (LPS) was established by 1H-NMR and 13C-NMR spectroscopy, including two-dimensional NOESY and H-detected 1H,13C heteronuclear multiple-quantum coherence (HMQC) experiments: -->2)-alpha-L-RhapI-(1-->2)-alpha-L-RhapII-(1-->4)-beta-D-++ +GalpA(I)-(1-->3)-beta-D-GlcpNAc-(1-->4)-alpha-D-GalpA(II)-(1-- >. In addition, an O-acetyl group was detected, which, most probably, is located at position 3 of a part of RhapI residues. Serological studies, using rabbit polyclonal anti-(P. vulgaris 032) serum, homologous and heterologous Proteus O-antigens and related artificial antigens, revealed the importance of an a-D-GalA-associated epitope in manifesting the immunospecificity of P. vulgaris 032 and substantiated serological relationships between the O-antigen studied and those of some other Proteus strains.

Carbohydrate Conformation↗
PubMed1999

Structure of the O-specific polysaccharide of a serologically separate strain Proteus penneri 2 from a new proposed serogroup O66.

O-specific polysaccharide chain of Proteus penneri strain 2 lipopolysaccharide was studied by full and partial acid hydrolysis, Smith degradation, methylation analysis, and NMR spectroscopy, including two-dimensional rotating-frame NOE spectroscopy (ROESY) and 1H,13C heteronuclear multiple-quantum coherence (HMQC) experiments. Together with D-glucose and 2-acetamido-2-deoxy-D-glucose, the polysaccharide was found to contain two rarely occurring sugars, 6-deoxy-L-talose (L-6dTal) and 2,3-diacetamido-2,3,6-trideoxy-L-mannose (L-RhaNAc3NAc), and the following structure of a non-stoichiometrically O-acetylated tetrasaccharide repeating unit was established: [equation: see text] The O-specific polysaccharide studied has a unique composition and structure and, accordingly, P. penneri 2 is serologically separate among Proteus strains. Therefore, we propose for P. penneri 2 a new Proteus O-serogroup O66 where this strain is at present the single representative.

Carbohydrate Conformation↗
PubMed2000

Structure of a 2-aminoethyl phosphate-containing O-specific polysaccharide of Proteus penneri 63 from a new serogroup O68.

Lipopolysaccharide of Proteus penneri strain 63 was degraded by mild acid to give a high molecular mass O-specific polysaccharide that was isolated by gel-permeation chromatography. Sugar and methylation analyses and NMR spectroscopic studies, including two-dimensional 1H, 1H COSY, TOCSY rotating-frame NOE spectroscopy, H-detected 1H,13C and 1H,31P heteronuclear multiple-quantum coherence (HMQC), and 1H, 13C HMQC-TOCSY experiments, demonstrated the following structure of the polysaccharide: where FucNAc is 2-acetamido-2,6-dideoxygalactose and PEtn is 2-aminoethyl phosphate. The polysaccharide studied shares some structural features, such as the presence of D-GlcNAc6PEtn and an alpha-L-FucNAc-(1-->3)-D-GlcNAc disaccharide, with other Proteus O-specific polysaccharides. A marked cross-reactivity of P. penneri 63 O-antiserum with P. vulgaris O12 was observed and substantiated by a structural similarity of the O-specific polysaccharides of the two strains. In spite of this, the polysaccharide of P. penneri 63 has the unique structure among Proteus O-antigens, and therefore a new, separate serogroup, O68, is proposed for this strain.

Carbohydrate Conformation↗
PubMed1996

Proteus syndrome associated with a sacrococcygeal teratoma; a rare combination.

We report on an 5-year-old boy with a Proteus syndrome known since his second year of life. Hidden in a lipomatous tumor we excised a sacrococcygeal teratoma which must have been present since birth. This is the first case, out of about 50 published Proteus cases, of a patient with Proteus syndrome and sacrococcygeal teratoma.

Bone Neoplasms↗
PubMed2006

Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection.

Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.

Arthritis, Rheumatoid↗
PubMed1975

Role of urease in pyelonephritis resulting from urinary tract infection with Proteus.

The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium.

Acute Disease↗
PubMed1988

Antibodies to Klebsiella and Proteus microorganisms in ankylosing spondylitis and rheumatoid arthritis patients measured by ELISA.

Antibodies to Klebsiella oxytoca and Proteus mirabilis in 21 active ankylosing spondylitis (AS), 13 active rheumatoid arthritis (RA), 19 inactive RA patients and 18 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Elevated anti-Klebsiella antibodies were demonstrated in active AS patients compared to active RA (p less than 0.01), inactive RA patients (p less than 0.001) and controls (p less than 0.005). When measuring antibodies to Proteus, active RA patients showed higher levels of antibodies compared to active AS patients (p less than 0.005) and healthy controls (p less than 0.05). Further investigations are required to assess the role of Klebsiella and Proteus microorganisms in AS and RA respectively.

Adult↗
PubMed1998

Pediatric peripheral neuropathy in proteus syndrome.

Proteus syndrome is a rare congenital disorder comprised of subcutaneous and internal hamartomas, pigmented skin nevi, skull exostoses, hemihypertrophy, and macrodactyly of the hands and feet. A 5-year-old girl diagnosed with Proteus syndrome presented with distal median compression neuropathy with the primary complaint of severe pain involving the left hand. Surgical exploration of the hand revealed a lipofibromatous hamartoma of the median nerve. The transverse carpal ligament was released and epineurectomy of the median nerve was performed. The patient remains symptom free at the 9-month follow-up. This report is the first description of a hamartoma directly involving a peripheral nerve in Proteus syndrome. Decompression of the nerve with the removal of the fibrofatty neural sheath resulted in the resolution of the symptoms in this patient. The surgeon should consider this approach as a potential first line of treatment before a more radical resection of the nerve is contemplated.

Child, Preschool↗
PubMed2001

Cerebriform fibrous proliferation vs. proteus syndrome.

Proteus syndrome is a rare, congenital hamartomatous syndrome that presents with a wide range of abnormalities. Regardless of different manifestations found in different patients, there exists three mandatory criteria for the diagnosis of this syndrome: a mosaic distribution of the lesions, a progressive course, and sporadic occurrence. When these criteria are met, the presence of additional connective tissue nevi, which are encountered mostly on the plantar surface of the feet, suffices for the diagnosis of Proteus syndrome. The authors present a 48-year-old woman who had been evaluated for a lesion on the plantar aspect of her left foot that was diagnosed as keloid and was treated unsuccessfully. In the light of the literature and with the help of histopathological reevaluation, the authors thought this unique lesion may be a localized form of Proteus syndrome.

Diagnosis, Differential↗
PubMed2002

Proteus syndrome in adulthood.

Proteus syndrome is a very rare congenital condition comprising malformations and overgrowth of multiple sorts of tissue. It was described for the first time in 1979 and was termed Proteus syndrome in 1983. The authors describe a 37-year-old patient who was diagnosed initially as having Klippel-Trenaunay-Weber syndrome at the age of 10 years. The patient was operated for a major thoracic lymphatic malformation, which caused functional problems. The operation at older age for this large lymphatic malformation proved to be complex. In addition, the authors address the difficulties in diagnosing Proteus syndrome. Vascular malformations causing functional problems in adulthood require major surgical procedures with a high risk of postoperative complications.

Adult↗
PubMed2005

Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning.

Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.

Child↗
PubMed1995

The detection of raised levels of IgM to Proteus mirabilis in sera from patients with rheumatoid arthritis.

An analysis by ELISA of 100 rheumatoid factor (RF)-positive sera selected at random from a collection of sera from patients with various auto-immune diseases and joint pains, and 100 RF-negative sera from the same collection matched by patient age and gender, showed that the RF-positive sera had highly significantly (p < 0.0001) raised levels of IgM antibody, but not IgG antibody, to Proteus mirabilis over those of the RF-negative sera. This response was subsequently found to be associated with sera from patients who clinically had rheumatoid arthritis (RA). Sera from the RA patients had significantly greater amounts (p = 0.026) of IgM antibody to P. mirabilis than to the other organisms tested and these values were also highly significantly different (p < 0.0001) from P. mirabilis IgM antibody levels in matched RF-negative sera. Sera from RA patients also had significantly greater amounts of IgA to P. mirabilis (p < 0.0001) and greater amounts of IgM to Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p < 0.0001) than those in matched RF-negative sera. Other classes of antibody to these organisms and all classes of antibody to Pseudomonas aeruginosa were not raised in the sera of RA patients over those of RF-negative controls. The IgM response in RA patients was not specific for only one O serotype of P. mirabilis but was associated with all 11 different O serotypes of P. mirabilis tested and those of other Proteus spp. Moreover, the IgM antibodies to Proteus spp. appeared to be independent from C-reactive protein and RF.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗
PubMed2003

An inducible tellurite-resistance operon in Proteus mirabilis.

Tellurite resistance (Te(r)) is widespread in nature and it is shown here that the natural resistance of Proteus mirabilis to tellurite is due to a chromosomally located orthologue of plasmid-borne ter genes found in enteric bacteria. The P. mirabilis ter locus (terZABCDE) was identified in a screen of Tn5lacZ-generated mutants of which one contained an insertion in terC. The P. mirabilis terC mutant displayed increased susceptibility to tellurite (Te(s)) and complementation with terC carried on a multicopy plasmid restored high-level Te(r). Primer extension analysis revealed a single transcriptional start site upstream of terZ, but only with RNA harvested from bacteria grown in the presence of tellurite. Northern blotting and reverse transcriptase-PCR (RT-PCR) analyses confirmed that the ter operon was inducible by tellurite and to a lesser extent by oxidative stress inducers such as hydrogen peroxide and methyl viologen (paraquat). Direct and inverted repeat sequences were identified in the ter promoter region as well as motifs upstream of the -35 hexamer that resembled OxyR-binding sequences. Finally, the 390 bp intergenic promoter region located between orf3 and terZ showed no DNA sequence identity with any other published ter sequences, whereas terZABCDE genes exhibited 73-85 % DNA sequence identity. The ter operon was present in all clinical isolates of P. mirabilis and Proteus vulgaris tested and is inferred for Morganella and Providencia spp. based on screening for high level Te(r) and preliminary PCR analysis. Thus, a chromosomally located inducible tellurite resistance operon appears to be a common feature of the genus Proteus.

Bacterial Proteins↗
PubMed1990

Immunological characterization of lipopolysaccharides from Proteus strains used in Weil-Felix test and reactivity with patient sera of tsutsugamushi diseases.

Immunological analyses of lipopolysaccharides (LPS) isolated from Proteus strains OX2, OX19, and OXK used as antigens of Weil-Felix (WF) test, were performed by quantitative agglutination, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. Antisera against LPS and whole cells (WC) of the three Proteus strains reacted with homologous LPS but not with heterologous LPS, and the reaction was inhibited by the O-polysaccharide fraction isolated from the homologous LPS except OX19-LPS, which lacked O-polysaccharide moiety. The immunological data support the findings that the O-polysaccharide moieties of LPS from OX2 and OXK strains possess different chemical composition (Mizushiri, Amano, Fujii, Fukushi, and Watanabe, Microbiol. Immunol. 34: 121-133, 1990). Antisera against Proteus strains reacted weakly with WC of Rickettsia prowazekii, Rickettsia typhi, and Rickettsia tsutsugamushi. Antisera from patients with tsutsugamushi disease reacted with OXK-WC by WF test when the sera were obtained 13 days after onset of fever. The immunoperoxidase (IP) test titers of these antisera began to rise 6 days after the onset of fever. By ELISA tests these antisera reacted with OXK-WC and OXK-LPS independently of the titers of WF or IP tests.

Antibodies, Bacterial↗