Proteus spp. as Putative Gastrointestinal Pathogens.

Proteus species, members of the Enterobacteriaceae family, are usually considered commensals in the gut and are most commonly recognized clinically as a cause of urinary tract infections. However, the recent identification of Proteus spp. as potential pathogens in Crohn's disease recurrence after intestinal resection serves as a stimulus to examine their potential role as gut pathogens. Proteus species possess many virulence factors potentially relevant to gastrointestinal pathogenicity, including motility; adherence; the production of urease, hemolysins, and IgA proteases; and the ability to acquire antibiotic resistance. Gastrointestinal conditions that have been linked to Proteus include gastroenteritis (spontaneous and foodborne), nosocomial infections, appendicitis, colonization of devices such as nasogastric tubes, and Crohn's disease. The association of Proteus species with Crohn's disease was particularly strong. Proteus species are low-abundance commensals of the human gut that harbor significant pathogenic potential; further investigation is needed.

Significance and Roles of Proteus spp. Bacteria in Natural Environments.

Proteus spp. bacteria were first described in 1885 by Gustav Hauser, who had revealed their feature of intensive swarming growth. Currently, the genus is divided into Proteus mirabilis, Proteus vulgaris, Proteus penneri, Proteus hauseri, and three unnamed genomospecies 4, 5, and 6 and consists of 80 O-antigenic serogroups. The bacteria are known to be human opportunistic pathogens, isolated from urine, wounds, and other clinical sources. It is postulated that intestines are a reservoir of these proteolytic organisms. Many wild and domestic animals may be hosts of Proteus spp. bacteria, which are commonly known to play a role of parasites or commensals. However, interesting examples of their symbiotic relationships with higher organisms have also been described. Proteus spp. bacteria present in soil or water habitats are often regarded as indicators of fecal pollution, posing a threat of poisoning when the contaminated water or seafood is consumed. The health risk may also be connected with drug-resistant strains sourcing from intestines. Positive aspects of the bacteria presence in water and soil are connected with exceptional features displayed by autochthonic Proteus spp. strains detected in these environments. These rods acquire various metabolic abilities allowing their adaptation to different environmental conditions, such as high concentrations of heavy metals or toxic substances, which may be exploited as sources of energy and nutrition by the bacteria. The Proteus spp. abilities to tolerate or utilize polluting compounds as well as promote plant growth provide a possibility of employing these microorganisms in bioremediation and environmental protection.

Case-control study of the risk factors for acquisition of Pseudomonas and Proteus species during tigecycline therapy.

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.

[THE USE OF PROBIOTICS IN PATIENTS WITH RHEUMATOID ARTHRITIS].

The results of biological research of colon microbiota of patients with rheumatoid arthritis (RA) is in article presented. The signs of III degree dysbiosis, by reducing the concentration of Bacteroides spp., Bifidobacterium spp., Lactobacillus spp. populations, typical strain E. coli. But over growth of populations Klebsiella spp., Proteus spp., Staphylococcus spp., atypical forms of E. coli, Candida spp. The scheme for the correction of the colon microflora of patients with (RA) by was proposed bifiform. Increasing of populations concentration of Bifidobacterium spp., Bacteroides spp., Lactobacillus spp., typical E. coli, Enterococcus spp. and selective decontamination of Enterococcus (Hly+), Klebsiella spp., Proteus spp., Staphylococcus spp., lactosonegative and E.coli (Hly+) confirmed after using of this eubiotics.

Sonication: a valuable technique for diagnosis and treatment of periprosthetic joint infections.

BACKGROUND: Periprosthetic joint infection (PJI) is the most severe complication, following joint arthroplasty. Identification of the causal microbial factor is of paramount importance for the successful treatment. PURPOSE: The aim of this study is to compare the sonication fluid cultures derived from joint prosthetic components with the respective periprosthetic tissue cultures. METHODS: Explanted prosthesis components for suspected infection were placed into a tank containing sterile Ringer's solution and sonicated for 1 minute at 40 kHz. Sonication fluid cultures were examined for 10 days, and the number and identity of any colony morphology was recorded. In addition, periprosthetic tissue specimens (>5) were collected and cultured according to standard practice. The duration of antimicrobial interruption interval before culture sampling was recorded. RESULTS: Thirty-four patients composed the study group. Sonication fluid cultures were positive in 24 patients (70.5%). Sixteen of thirty four periprosthetic tissue cultures (47.1%) were considered positive, all revealing the same microbial species with the respective sonication fluid cultures: 3 tissue samples showed polymicrobial infection. All tissue cultures were also found positive by the sonication fluid culture. CONCLUSIONS: Sonication fluid cultures represent a cheap, easy, accurate, and sensitive diagnostic modality demonstrating increased sensitivity compared to periprosthetic tissue cultures (70.5 versus 47.1%).

The prevailing O serogroups among the serologically differentiated clinical Proteus spp. strains in central Poland.

In the years 2006-2011, 617 Proteus spp. strains isolated mostly from urine and wounds or other clinical sources were collected in Lódz, Poland, to determine the offensive O serotypes frequently occurring among patients. P. mirabilis exhibited the most intensive swarming growth and was dominating species (86.9%), followed by P. genomospecies, P. vulgaris, and P. penneri. Ninety four per cent strains were recognized as S (smooth) forms. Serological studies (involving ELISA-enzyme-linked immunosorbent assay and Western blotting using native and adsorbed rabbit antisera) enabled classification of 80% S isolates into respective Proteus O serogroups among the 83 ones, described so far. The remaining strains seemed to be serologically unique. Despite the observed big serological variety of Proteus spp. isolates, we found the O78 serogroup recently described in Poland as dominating and identified other widespread serotypes: O3, O6, O10, O11, O27, O28, and O30 reported earlier as predominating also in other countries; O77 and O79 detected lately in Poland; O16, O18, O20, and O50. No unique structural feature of the prevalent O serotypes has been indicated. However, the prevalence of some O serogroups indicates that particular serotypes may be in some ways beneficial to the strains producing these kinds of O antigen.

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.

Professor Krystyna Kotelko and her contribution to the study of Proteus endotoxin.

Professor Krystyna Kotelko was working as a microbiologist at the University of Lódz (Poland). Her main object of study was the LPS (endotoxin) of opportunistic urinary pathogens from the genus Proteus. She demonstrated, for the first time, the presence of uronic acids and amino acids, as well as two heptoses (L- glycero-D- manno-heptose and D- glycero-D- manno-heptose) and hexosamines in Proteus LPS, and developed a classification scheme of the Proteus LPS into chemotypes. Prof Kotelko also initiated studies on the chemical structure of Proteus O-specific polysaccharide and investigations on the serological specificity of this part of LPS, as well its core region. She also analysed the virulence factors of these bacteria, such as haemolysin and invasiveness.

Bacterial interference induced in embryonated eggs by staphylococci.

Studies of experimental infections in embryonated eggs demonstrated that prior allantoic infection with avirulent staphylococci afforded significant protection against subsequent challenge with virulent strains. All strains of coagulase-positive and coagulase-negative staphylococci tested that were relatively avirulent for embryonated eggs were capable of producing interference. The interference induced afforded protection not only against challenge with virulent staphylococci, but also against Diplococcus pneumoniae, Salmonella typhimurium, Escherichia coli, Proteus mirabilis, and one strain of influenza virus (A(2)J 305). Prior allantoic infection with avirulent staphylococci also protected against intravenous as well as allantoic infection with challenge strains.Interference required infection with viable bacteria. The onset of interference appeared within a few minutes after injection of the interfering strain, but was not maximal until 24 hours had elapsed between injection of the interfering and challenge strains. The protection afforded by the production of interference could not be overcome by increased inoculum size of the challenge strain and extended even to challenge with 10(9) bacteria. Studies of in vitro and in vivo growth of challenge strains in allantoic fluid demonstrated that some interfering strains inhibited growth of the challenge strains. Other strains produced interference without producing prolonged inhibition of the growth of challenge strains. Similarly, interference could not be attributed to attenuated virulence of the challenge organisms. All interfering strains studied produced enhanced bactericidal activity of whole blood from the affected embryos, but whether this affected leukocyte activity, opsonization, or other host defense mechanisms has yet to be determined.

Mannose-resistant Proteus-like and P. mirabilis fimbriae have specific and additive roles in P. mirabilis urinary 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.

[Proteus bacilli: features and virulence factors]. / Bakterie z rodzaju Proteus--cechy i czynniki chorobotwórczosci.

In this article, different aspects of virulence factors of Proteus bacilii (P. mirabilis, P. vulgaris, P. penneri i P. hauseri) are presented. These are opportunistic pathogens that cause different kinds of infections, most frequently of the urinary tract. These bacteria have developed several virulence factors, such as adherence due to the presence of fimbriae or afimbrial adhesins, invasiveness, swarming phenomenon, hemolytic activity, urea hydrolysis, proteolysis, and endotoxicity. Below we focus on data concerning the molecular basis of the pathogenicity of Proteus bacilli.

The Burden of Comorbidity Is Associated with Antibiotic Resistance Among Institutionalized Elderly with Urinary Infection: A Retrospective Cohort Study in a Single Italian Nursing Home Between 2009 and 2014.

Urinary tract infections (UTIs), which are common among nursing home patients, are associated with adverse outcomes and increased healthcare costs. Antibiotic resistance is an emerging problem, associated with excess morbidity and mortality; it has been suggested that this condition might be more prevalent among subjects with comorbid conditions. The aim of this study was to assess the association, if any, of antibiotic resistance with the burden of comorbidity in elderly with UTIs. This retrospective study enrolled 299 patients with culture-positive UTI consecutively admitted to the nursing home of the "Fondazione San Raffaele Cittadella della Carità", Taranto, Italy, which includes 80 beds under the direction of two geriatricians. The burden of comorbidity was quantified using the Charlson comorbidity score index. Diagnosis of UTI was ascertained by urine culture. Antibiotic resistance was defined according to the European Centre for Disease Prevention and Control expert proposal. Logistic regression was used to assess the adjusted association of the variables of interest with the presence of antibiotic resistance. Antibiotic resistance was detected in 162/299 (54%) patients. In logistic regression, the presence of antibiotic resistance was independently associated with higher Charlson score, after adjusting (odds ratio = 1.06; 95% confidence interval = 1.01-1.10). Antibiotic resistance is highly prevalent among nursing home residents; it is associated with the burden of comorbidity, but not with single diseases. This association and its potential implications should be assessed in dedicated studies.

Prognosis Risk of Urosepsis in Critical Care Medicine: A Prospective Observational Study.

This study aimed to investigate the clinical features of urosepsis and to raise awareness of this problem. Of the 112 sepsis patients enrolled, 36 were identified as having urosepsis. The bacteria involved in the infection leading to urosepsis included Escherichia coli, Proteus species, Enterococcus species, Klebsiella species, other Gram-positive cocci, and Pseudomonas aeruginosa. Although the organ/system dysfunction appeared earlier in the urosepsis patients than in the other sepsis patients (4.7 ± 2.4 versus 7.2 ± 4.5 hours, P < 0.001), the urosepsis patients presented with a better prognosis and lower 28-day mortality rate than the others (6% versus 37%). In the multivariate analysis, the type of sepsis (urosepsis, OR = 0.019, 95% CI = 0.001, 0.335, P = 0.007) and SOFA score (OR = 1.896, 95% CI = 1.012, 3.554, P = 0.046) remained significantly associated with the survival. The time of admission to the intensive care unit of 17 patients transferred from the Department of Urinary Surgery was significantly prolonged compared with those transferred from other departments (11.6 ± 7.3 versus 7.2 ± 4.9 hours, P < 0.05). In conclusion, urosepsis suggested a better prognosis, but attention needs to be paid in clinical practice, especially in urinary surgery.

Insights into copper effect on Proteus hauseri through proteomic and metabolic analyses.

This is the first-attempt to use liquid chromatography coupled with tandem mass (LC-MS-MS) in deciphering the effects of copper ion on Proteus hauseri. Total 941 proteins in copper-addition (+Cu) group and 898 proteins in non-copper-addition (-Cu) group were found, which containing 221 and 178 differential proteins in +Cu and -Cu group, respectively. Differential proteins in both groups were defined into 14 groups by their functional classification which transport/membrane function proteins were the major different part between the two groups, which took 19.5% and 7.7%, respectively. The result of BioCyc and KEGG analyses on metabolic pathway indicated that copper could interrupted the pathway of chemotaxis CheY and inhibited the swarming of P. hauseri, which provided a potential in controlling the pathogenicity of this strain.

The ureases of Proteus strains in relation to virulence for the urinary tract.

The ureases produced by a large number of strains of different Proteus species, some of which were known to have a special affinity for the urinary tract, were examined by polyacrylamide-gel electrophoresis. Each Proteus strain gave a pattern of urease isoenzymes that was characteristic and unique to its species although strains of P. Mirabilis and P. vulgaris gave isoenzyme patterns that were closely similar. There was some minor variation in the patterns of urease isoenzymes even between strains of the same species. This was most noticeable among P. rettgeri strains and to a lesser extent among P. vulgaris strains. No correlation was found between the types of ureases a strain produced and its pathogenicity for the urinary tract.

Proteus morgani is less frequently associated with urinary tract infections than Proteus mirabilis--an explanation.

The metabolic activities of faecal and urinary strains of Proteus morgani and P. mirabilis were compared. Regardless of origin, the generation time of P. morgani strains in urine was approximately twice as long as that of the P. mirabilis strains. Urease synthesis was constitutive in P. morgani strains but required induction with urea in the P. mirabilis strains. In the presence of urea, the P. mirabilis strains liberated ammonia more rapidly and produced alkaline conditions more quickly than P. morgani strains, although they synthesized much less urease. These characteristics may place P. morgani strains at a disadvantage in comparison with P. mirabilis strains in their ability to cause urinary tract infections.

Production and properties of haemolysins from clinical isolates of the Proteeae.

A collection of 198 clinical isolates of strains belonging to the tribe Proteeae was examined for haemolytic activity on blood agar and in Brain Heart Infusion Broth. The strains were of diverse bacteriocin and O-antigenic types and from a wide variety of sources. They included representatives of all species of Morganella, Proteus and Providencia. Approximately half of the M. morgani strains were haemolytic on blood agar. This activity was not associated with any particular bacteriocin type. The haemolysin was also produced during exponential growth in broth and was thermolabile and calcium dependent. All P. mirabilis strains and some P. vulgaris strains were non-haemolytic on blood agar. However, most strains of the Proteus spp., irrespective of their bacteriocin and antigenic type, produced, over a short period during exponential growth in broth, a heat-stable, cell-associated calcium-independent haemolysin. A smaller proportion of P. vulgaris and P. penneri strains produced, in addition, a thermolabile, calcium-dependent haemolysin which was associated with the formation of large haemolytic zones on blood agar. The relationship of these haemolysins to Escherichia coli haemolysin and their possible role in virulence is discussed. Haemolysin production was not found in any of the 74 strains of four species of Providencia.

The production of HlyA toxin by Proteus penneri strains.

Twelve diverse strains of Proteus penneri of clinical origin all produced a calcium-dependent haemolysin, unlike most other Proteus spp. In most strains the haemolysin was secreted into the medium during early exponential growth and lysed not only of a variety of erythrocyte types from several animals including man, but also human neutrophils and human embryo lung fibroblasts. The haemolysin was a protein of 107 kDa, the same size as Escherichia coli HlyA, and it reacted with antiserum to E. coli HlyA. Because of its similarity in size, antigenicity and range of action to the HlyA virulence factor of E. coli, P. penneri HlyA is believed to be an important virulence factor for this organism. It was degradable by an EDTA-sensitive protease--probably the IgA protease--to inactive fragments. The interaction of P. penneri HlyA and IgA protease in vivo and the origin of HlyA, which has now been found in many diverse bacteria, are discussed.

Biological activities of lipopolysaccharides of Proteus spp. and their interactions with polymyxin B and an 18-kDa cationic antimicrobial protein (CAP18)-derived peptide.

The saccharide constituents of lipopolysaccharides (LPS) of Proteus spp. vary with the strain and contain unique components about which little is known. The biological activities of LPS and lipid A from S- and R-forms of 10 Proteus strains were examined. LPS from all S-form Proteus strains was lethal to D-(+)-galactosamine (GalN)-loaded, LPS-responsive, C3H/HeN mice, but not to LPS-hypo-responsive C3H/HeJ mice. P. vulgaris 025 LPS evoked strong anaphylactoid reactions in N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-primed C3H/HeJ mice. LPS from S- and R-form Proteus strains induced production of nitric oxide (NO) and tumour necrosis factor (TNF) by macrophages isolated from C3H/HeN but not C3H/HeJ mice. Lipid A from Proteus strains also induced NO and TNF production, although lipid A was less potent than LPS. The effects of LPS were mainly dependent on CD14; LPS-induced NO and TNF production in CD14+ J774.1 cells was significantly greater than in CD14-J7.DEF.3 cells. All LPS from Proteus strains, and especially from P. vulgaris 025, exhibited higher anti-complementary activity than LPS from Escherichia coli or Pseudomonas aeruginosa. Polymyxin B inactivated proteus LPS in a dose-dependent manner, but these LPS preparations were more resistant to polymyxin B than E. coli LPS. CAP18(109-135), a granulocyte-derived peptide, inhibited proteus LPS endotoxicity only when the LPS:CAP18(109-135) ratio was appropriate, which suggests that CAP18(109-135) acts through a different mechanism than polymyxin B. The results indicate that LPS from Proteus spp. are potently endotoxic, but that the toxicity is different from that of LPS from E. coli or Salmonella spp. and even varies among different Proteus strains. The variation in biological activities among proteus LPS may be due to unique components within the respective LPS.