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Resistance to beta-lactam antibiotics Proteus strains.

A total of 218 Proteus strains isolated from clinical sources were tested for their susceptibility to three penicillins and two cephalosporins. The ability to beta-lactamase production was examined in 36 of these strains. Proteus mirabilis strains were generally more susceptible to cephalosporins than to penicillins, whereas indole-positive Protei were almost uniformely resistant to cephalosporins as well as to ampicillin and benzylpenicillin but susceptible to carbenicillin. Fairly good correlation was found between the amount and hydrolytic soectryn if beta-lactamase activity and the pattern of resistance to penicillins and cephalosporins in the strains examined. Some observations indicate, however, that the resistance of Proteus bacilli to this group of antibiotics is partly related to permeability barriers in bacterial cell. About 37% of Proteus strains transferred their ampicillin resistance to E. coli K12. Beta-lactamase activities mediated by R plasmids in E. coli cultures were 1.5 to 5 times higher than in respective Proteus donors.

Ampicillin↗

[Synergism of colistin and sulfonamide in proteus species (author's transl)].

In agar diffusion testing of Proteus mirabilis strains sensitive to sulfonamide a synergistic effect of colistine (C) and sulfonamide (S) was demonstrated. By quantitative evaluation these results were confirmed in 100 strains of Proteus mirabilis and 100 strains of indol-positive Proteus spp. using broth dilution method. Combining 1 part C with 10 parts S the mean increase in sulfonamide sensitivity was enhanced fourfold. Increasing the inoculum sensitivity of Proteus against the combination of C and S was still found to range within therapeutic blood levels. Therefore in treatment of Proteus infection the positive synergistic effect of C+S should be taken into consideration.

Colistin↗

Structural studies on the lipopolysaccharide core of Proteus OX strains used in Weil-Felix test: a mass spectrometric approach.

The core region of the lipopolysaccharides of Proteus group OX bacteria, which are used as antigens in Weil-Felix test for serodiagnosis of rickettsiosis, were studied by chemical degradations in combination with ESI FTMS, including infrared multi-photon dissociation (IRMPD) MS/MS and capillary skimmer dissociation. Structural variants of the inner core region were found to be the same as in Proteus non-OX strains that have been studied earlier. The outer core region has essentially the same structure in Proteus vulgaris OX19 (serogroup O1) and OX2 (serogroup O2) and a different structure in Proteus mirabilis OXK (serogroup O3). A fragmentation due to the rupture of the linkage between GlcN or GalN and GalA was observed in IRMPD-MS/MS of core oligosaccharides and found to be useful for screening of Proteus strains to assign structures of the relatively conserved inner core region and to select for further studies strains with distinct structures of a more variable outer core region.

Carbohydrate Sequence↗

Plasmid-mediated multiple antibiotic resistance in Proteus mirabilis isolated from patients with urinary tract infection.

BACKGROUND: Worldwide surveillance of antimicrobial resistance among urinary tract pathogens is useful to determine important trends and geographical variation for common Gram negative and positive species. We initiated this study to learn the drug resistance pattern and its location (genomic or plasmid-borne) among the strains of Proteus mirabilis, one of the most common causative agents of urinary tract infection (UTI). MATERIAL/METHODS: A total of 200 urine samples were collected from UTI patients, followed by isolation and identification of Proteus milabilis strains. Antibiotic sensitivity and resistance analysis was performed by the disc diffusion method, employing multiple antibiotic discs. The sensitivity was monitored by visualizing the zone of inhibition around the disc. Plasmid isolation was performed by the method of Kado and Liu. Transfer of the R-Plasmid to recipient E.coli C600 cells was achieved using the method of Lederberg and Cohen. RESULTS: Clinical study revealed that this infection is more common in young pregnant women. Various strains of Proteus mirabilis isolated during the course of the study were found to show multiple antibiotic resistance, which was further characterized as plasmid-borne drug resistance. CONCLUSIONS: Proteus mirabilis is one of the important causative agents of urinary tract infection in young women especially during the state of pregnancy. Multiple antibiotic resistance markers of Proteus strains were identified as plasmid mediated.

Adolescent↗

[Prevalence of multidrug-resistant Proteus spp. strains in clinical specimens and their susceptibility to antibiotics].

Proteus sp. are opportunistic microorganisms which cause urinary tract and wounds infections, bacteriaemia and sepsis. The aim of this study was analysis of prevalence of multidrug-resistant Proteus sp. strains in clinical specimens and evaluation of their susceptibility to selected antibiotics. The study was carried out of 1499 Proteus sp. strains were isolated in 2000-2003 from patients of departments and dispensaries of the University Hospital CM in Bydgoszcz UMK in Torun. The strains were identified on the basis of appearance of bacterial colonies on bloody and McConkey's agars, movement ability, indole and urease production and in questionable cases biochemical profile in ID GN or ID E (bio-Mérieux) tests was also included. Antibiotic susceptibility was tested by disk diffusion method. Isolated strains were regarded as multidrug-resistant when they were resistant to three kinds of antibiotics at least. Received Proteus sp. the most frequently belonged to P. mirabilis species (92.3%). Most of these bacteria were isolated from urine from patients of Rehabilitation Clinic. All of multidrug-resistant strains were resistant to penicillins and cephalosporins, 98.9% to co-trimoxazole, 77.7% to quinolones, 63.8% to tetracyclines, 38.5% to aminoglycosides, 19.3% to monobactams and 3.4% to carbapenems. Almost 25% multidrug-resistant Proteus sp. produced ESBL.

Drug Resistance, Multiple, Bacterial↗

[Investigations made to test the demarcation line method (DLM) after Dienes for its suitability in the epidemiology of Proteus mirabilis (author's transl)].

In 1946, DIENES observed that non-identical Proteus-strains, when swarming towards each other, were froming distinctly demarcated lines ("DIENES' phenomenon", demarcation (=AGL) phenomenon). Strains of the same origin were amalgamating without demarcation. In 1970, STURDZA studied this phenomenon and commented on its relevance for the epidemiology of nosocomial Proteus-infections. An increased number of Proteus-infections in Berlin was the reason that this procedure was tested for epidemiological purposes. Approx. 300 Proteus mirabilis-strains, tested on normal meat fluid agar, could be divided into 52 AGL-groups. When tested by several investigators, the coordination to any AGL-group seemed to be very subjective. Consequently, a DNase-agar with o-toluidinblue as an indicator, as had been mentioned by CHAMBERS in 1975, was used in order to give a more exact demonstration of AGL. This resulted in a reduction from 52 to 42 AGL-groups. Another 140 newly isolated Proteus-strains belonged to the 42 known as well as to another 42 new AGL-groups. Whether these 84 AGL-groups possess the constancy which is imperative for practical purposes, is however, still rather doubtful.

Agar↗

[Further types of core lipopolysaccharides in Proteus].

Comparative analysis of the chemical composition of 11 core oligosaccharides isolated from lipopolysaccharides of the wild (S) and phenotypically rough (R) strains Proteus mirabilis (nine) and Proteus vulgaris (two) allowed to recognize three new types Proteus core, classified as IV, V, VI. All of them contained D-galactose and D-galactosamine in addition to common core constituents: D-glucose, D-galacturonic acid, L-glycero-D-manno-heptose, KDO, EtN described for Proteus core types I, II, III (6, 7, 8). D-glucosamine was characteristic for Proteus core type VI whereas D-glycero-D-manno-heptose for types V and VI.

Oligosaccharides↗

Potential virulence factors of Proteus bacilli.

The object of this review is the genus Proteus, which contains bacteria considered now to belong to the opportunistic pathogens. Widely distributed in nature (in soil, water, and sewage), Proteus species play a significant ecological role. When present in the niches of higher macroorganisms, these species are able to evoke pathological events in different regions of the human body. The invaders (Proteus mirabilis, P. vulgaris, and P. penneri) have numerous factors including fimbriae, flagella, outer membrane proteins, lipopolysaccharide, capsule antigen, urease, immunoglobulin A proteases, hemolysins, amino acid deaminases, and, finally, the most characteristic attribute of Proteus, swarming growth, enabling them to colonize and survive in higher organisms. All these features and factors are described and commented on in detail. The questions important for future investigation of these facultatively pathogenic microorganisms are also discussed.

Bacterial Outer Membrane Proteins↗

The nature of colicin K from Proteus mirabilis.

The colicinogenic factor K has been transferred from E. coli K 235 to Proteus mirabilis. The DNA of the colicinogenic Proteus has been shown to contain a small amount of a satellite DNA which presumably harbors the Col K factor. In the presence of mitomycin C the colicinogenic Proteus secretes colicin K into the growth medium. The bacteriocin has been purified by chromatography and obtained as an immunologically homogeneous substance unconjugated with other antigens of the Proteus bacillus. Proteus colicin K is a protein of relatively low molecular weight. It contains all of the usual amino acids except cysteine and is free of lipids and polysaccharides. The bacteriocin can be separated by electrofocusing into two major components. The latter have the same biological properties but differ in their specific electrical charges.

Amino Acids↗

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis.

OBJECTIVE: Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. METHODS: Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor (RF)-positive RA, 16% RF-negative RA, 17% a spondyloarthropathy and 37% undifferentiated arthritis. Serum antibodies to P. mirabilis, Escherichia coli and other potentially arthritogenic organisms (Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia and parvovirus B19) and for antibodies specific for immunoglobulin (Ig) G damaged with advanced glycation end-products (anti-IgG-AGE) were measured. RESULTS: IgM and IgA anti-Proteus antibodies were significantly higher in patients with RF-positive RA compared with all other patient groups (P < 0.0005 and P < 0.005). Anti-P. mirabilis IgG, and IgG, IgA, and IgM antibodies to other potentially arthritogenic pathogens did not differ in the patient groups. IgM antibodies to E. coli were elevated in RF-positive RA patients. Anti-P. mirabilis IgM and IgA results were not explained by false-positive reactions, because after absorption of RF there was no decrease in antibodies to Proteus in 10 of 12 patients. Proteus and E. coli antibodies were highest in patients positive for both RF and anti-IgG-AGE antibodies (P<0.001). Patients with erosions tended to have higher IgA anti-Proteus titres, but no association with the shared HLA epitope or treatment was detected. CONCLUSION: Anti-P. mirabilis IgM and IgA and anti-E. coli IgM antibody elevations are associated with early seropositive RA and the presence of anti-IgG-AGE antibodies. The role that P. mirabilis or E. coli plays in early RF-positive RA requires further investigation.

Adult↗

Scoliosis in Proteus syndrome: case report.

STUDY DESIGN: The case of patient with scoliosis based on a rare hamartomatous, Proteus syndrome, is reported. OBJECTIVES: To present the characteristics of scoliosis associated with Proteus syndrome, and to investigate the mechanisms that cause it. SUMMARY OF BACKGROUND DATA: Proteus syndrome, a rare hamartomatous disorder first coined by Wiedemann, manifests many clinical morphologic abnormalities including scoliosis. The characteristics and cause of scoliosis in this syndrome are fully unknown. METHODS: A patient with Proteus syndrome was followed from the age of 3 months to the age of 21 years. This patient received spinal corrective surgery for severe scoliosis. Detailed investigations of the scoliosis as well as the physical and imaging examinations were performed to characterize the scoliosis. RESULTS: Computed tomography showed exclusive asymmetric appearance of lumbar spine, hypertrophy of the only right facet joints, and pedicles at L1-L4, which accorded with the right-side hemihypertrophy of the patient's extremities. CONCLUSIONS: Scoliosis with Proteus syndrome seems to be based on hemihypertrophy, with no influence of mechanical stress.

Humans↗

Role of RsmA in the regulation of swarming motility and virulence factor expression in Proteus mirabilis.

Swarming by Proteus mirabilis involves differentiation of typical short vegetative rods into filamentous hyper-flagellated swarm cells that undergo cycles of rapid and co-ordinated population migration across surfaces and exhibit high levels of virulence gene expression. RsmA (repressor of secondary metabolites) and CsrA, its homologue in Escherichia coli, control many phenotypic traits, such as motility and pathogenesis in Erwinia species, glycogen biosynthesis, cell size and biofilm formation in Escherichia coli and swarming motility in Serratia marcescens. To investigate the role of RsmA in Proteus mirabilis, the rsmA gene from Proteus mirabilis (hereafter referred to as rsmA(Pm)) was cloned. RsmA(Pm) showed high sequence similarity to Escherichia coli CsrA and RsmA cloned from Erwinia carotovora subsp. carotovora, Serratia marcescens, Haemophilus influenzae and Bacillus subtilis and could complement an Escherichia coli csrA mutant in glycogen synthesis. A low-copy-number plasmid carrying rsmA(Pm) expressed from its native promoter caused suppression of swarming motility and expression of virulence factors in Proteus mirabilis. mRNA stability assays suggested that RsmA(Pm) inhibited virulence factor expression through promoting mRNA degradation. RsmA homologues cloned from Serratia marcescens and Erwinia carotovora subsp. carotovora could also inhibit swarming and virulence factor expression in Proteus mirabilis.

Amino Acid Sequence↗

The core region of Proteus mirabilis R110/1959 lipopolysaccharide.

The complete core structure present in the lipopolysaccharide of the R mutant R110/1959 from Proteus mirabilis (Proteus type II core) was investigated using methylation analysis and a number of degradation methods such as Smith degradation and beta-elimination. These studies combined with earlier work on a Rc-type mutant of P. mirabilis O28 (R4/O28) which shares the same inner core region, allowed formulation of the complete core structure of the Proteus type II core as shown in Scheme 1. (formula; see text) A characteristic feature of the Proteus core of type II is the presence of two units of D-galacturonic acid (DGalA); one in terminal, the other one in a chain-linked position. In addition, the presence of the two isomers of glycero-D-manno-heptose (LDHep and DDHep) and the lack of galactose are conspicuous. DDHep occupies a terminal position in the external core region, whereas the three units of LDHep in addition to dOclA form, as in other enterobacterial core types, the internal core region. The taxonomic significance of the presence of DGalA in the Proteus type II core, but also in all R cores of other Proteeae investigated so far, will be discussed.

Carbohydrate Conformation↗

Proteus penneri isolated from the pus of a patient with epidural abscess.

P. mirabilis and P. vulgaris are the two wellknown species in the genus Proteus. P. myxofaciens and P. penneri are recent additions to the genus. We isolated P. penneri from the pus of a patient with suppurative otitis media and an epidural abscess. The characteristics of the organism, including morphology, staining, physiology and biochemistry, were studied. Clinical microbiological laboratories should suspect P. penneri in the case of as Proteus strain that is negative for indole, salicin and esculin, but otherwise resembles P. vulgaris. Proteus penneri, formerly known as Proteus vulgaris indole-negative or as Proteus vulgaris biogroup 1, was named by Hickman et al in 1932. Little information about human infection by this organism is available. In 1982, Hickman and co-workers studied 20 strain of P. penneri which were isolated from clinical specimens (urine, stool, etc.) in the USA. However, its clinical significance, until recently, was unknown. We isolated a strain of P. penneri from the pus of a patient with suppurative otitis media and an epidural abscess on June 10 and 15, 1989. This paper concerns the problems encountered in identifying this organism and its clinical significance.

Abscess↗

Metabolic variations of Proteus in the Memphis area and other geographical areas.

The number of strains of Proteus studied was 413, and these were obtained from all clinical materials with the exception of fecal specimens. Lactose was fermented by 37 strains (P. inconstans, 29%; P. rettgeri, 16%; P. mirabilis, 4.2%; P. morganii, 3.6%; and P. vulgaris, 0%) of which 33 were from the genitourinary system. These 33 strains constituted 12.7% of the 260 strains isolated from this source. Biochemically, P. mirabilis was the least variable, and P. rettgeri was the most variable of the five species of Proteus tested. P. inconstans and P. rettgeri resembled each other more closely than any of the other species of Proteus. Comparison of results obtained in the Memphis area with those found in other locations showed that biochemical characteristics varied most with the substances citrate, salicin, xylose, trehalose, and mannitol. In contrast to earlier reports from Israel and England, none of the strains of P. inconstans in the present study was able to attack urea. All five species of Proteus tested (by the disc method) were highly susceptible to methenamine mandelate. P. mirabilis, P. morganii, and P. vulgaris were also highly susceptible to nitrofurantoin. All strains of P. mirabilis were susceptible to ampicillin. P. inconstans was the most resistant species of Proteus. Of the other 356 urease-positive strains tested, 79% were susceptible to chloramphenicol, whereas only 3.8% of the 56 urease-negative strains (P. inconstans) were susceptible. When tested with streptomycin, 61% of urease-positive strains were susceptible and 1.8% of the urease-negative strains were susceptible. Of 36 lactose-positive strains, 33.8% were susceptible to chloramphenicol, whereas 72.8% of all lactose-negative strains were susceptible. Again, of the lactose-positive strains, 17% were susceptible to streptomycin, whereas 56.3% of all lactose-negative strains were susceptible.

Anti-Bacterial Agents↗

The HpmA hemolysin is more common than HlyA among Proteus isolates.

Two different hemolysins, HpmA and HlyA, have been reported in Proteus spp. To study the distribution of these hemolysins among Proteus strains, isolates from various infections and normal feces were screened for hemolysin production. All 63 Proteus mirabilis strains and 23 of the 24 Proteus vulgaris strains produced a calcium-independent hemolytic activity detectable in cell-free supernatants. The calcium-independent activity was due to HpmA; this activity correlated with the presence of hpmA sequences and the production of an extracellular 166-kilodalton (kDa) protein that reacted with anti-HpmA antiserum. HpmA- mutants, constructed by deletion of the central portion of the hpmA gene, did not produce the 166-kDa protein and were no longer hemolytic when compared with their respective parent strains. Among the 87 P. mirabilis and P. vulgaris isolates examined, calcium-dependent hemolytic activity was produced by only two P. vulgaris strains. These strains produced a 110-kDa protein which comigrated with the Escherichia coli hemolysin (HlyA) antibodies in immunoblots. These studies show that Proteus spp. produce two distinct extracellular hemolysins, with nearly all strains producing the calcium-independent hemolysin, HpmA, but only an occasional P. vulgaris isolate producing HlyA.

Bacterial Proteins↗

Shared amino acid sequences between major histocompatibility complex class II glycoproteins, type XI collagen and Proteus mirabilis in rheumatoid arthritis.

OBJECTIVES: To show molecular similarity between two sequences of Proteus mirabilis (haemolysin--ESRRAL; urease--IRRET) with HLA-DR antigens (EQRRAA) which are associated with rheumatoid arthritis (RA) and type XI collagen (LRREI), respectively; and, in patients with RA, to measure levels of antibody against a 16-mer synthetic peptide containing the ESRRAL sequence, and the haemolysin and urease proteins of Proteus mirabilis. METHODS: The homologous sequences EQRRAA and ESRRAL were modelled with Alchemy III, using the crystalline structure of DRB1*0101 (HLA-DR1). Sera from 40 patients with RA, 30 with ankylosing spondylitis (AS), and 30 controls were tested against synthetic ESRRAL peptide and the haemolysin of Proteus mirabilis by enzyme linked immunosorbent assay. Similar tests were also carried out on sera from 20 patients with RA, 40 with AS, and 15 controls, against Proteus mirabilis urease. RESULTS: Molecular modelling of the homologous sequences ESRRAL/EQRRAA and IRRET/LRREI showed stereochemical similarities. Antibodies to the 16-mer synthetic peptide containing the ESRRAL sequence, the haemolysin, and urease proteins were significantly increased in RA patients compared with AS patients (p < 0.001) and healthy controls (p < 0.001). No such increases were observed with three control peptides including the EDERAA sequence of DRB1*0402 (HLA-DR4/Dw10), the haemolysin proteins of Streptococcus pyogenes and Vibrio parahaemolyticus, and the urease of Bacillus pasteurii. CONCLUSION: The additive effect of the immune responses to the two Proteus mirabilis antigens, haemolysin (ESRRAL) and urease (IRRET), could be relevant in the aetiopathogenesis of RA.

Adult↗

Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet.

OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.

Antibodies, Bacterial↗