Potential Probiotics Bacillus subtilis KATMIRA1933 and Bacillus amyloliquefaciens B-1895 Co-Aggregate with Clinical Isolates of Proteus mirabilis and Prevent Biofilm Formation.

A urinary tract infection (UTI) is a multi-factorial disease including cystitis, pyelonephritis, and pyelitis. After Escherichia coli, Proteus mirabilis is the most common UTI-associated opportunistic pathogen. Antibiotic resistance of bacteria and infection recurrence can be connected to biofilm formation by P. mirabilis. In this study, human and sheep isolates of P. mirabilis were investigated for antibiotic sensitivity using an antibiotic disk test. Co-aggregation of the tested potential probiotic bacilli, Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933, with the isolated pathogen was also evaluated. Then, the anti-biofilm activity of naturally derived metabolites, such as subtilin and subtilosin, in the bacilli-free supernatants was assessed against biofilms of P. mirabilis isolates. The isolated pathogens were sensitive to 30 µg of amikacin and 5 µg of ciprofloxacin but resistant to other tested antibiotics. After 24 h, auto-aggregation of B. amyloliquefaciens B-1895 was at 89.5% and higher than auto-aggregation of B. subtilis KATMIRA1933 (59.5%). B. amyloliquefaciens B-1895 strongly co-aggregated with P. mirabilis isolates from human UTIs. Cell-free supernatants of B. amyloliquefaciens B-1895 and B. subtilis KATMIRA1933 showed higher antimicrobial activity against biofilms of P. mirabilis isolated from humans as compared with biofilms of sheep isolates. According to our knowledge, this is the first report evaluating the anti-biofilm activity of probiotic spore-forming bacilli against clinical and animal UTI isolates of P. mirabilis. Further studies are recommended to investigate the anti-biofilm activity and the mode of action for the antimicrobial substances produced by these bacilli, subtilosin and subtilin.

Independent Transurethral Urinary Tract Inoculation in a Murine Model of Ascending Infection with Proteus mirabilis.

Live animal modeling enables more in-depth realistic methods for studying the pathogenesis of urinary tract infections. Initiating a transurethral urinary tract infection in the female mouse is a challenging endeavor. However, when done with consistency and care, this infection model yields irreplaceable data. The methods necessary to ensure successful mouse transurethral inoculation and colonization in a single strain infection model with Proteus mirabilis are presented here.

Indwelling Urinary Catheter Model of Proteus mirabilis Infection.

Uncomplicated urinary tract infections, especially those caused by Escherichia coli, have historically been widely studied. However, complicated urinary tract infections are presenting ever increasing healthcare challenges, particularly with Proteus mirabilis. P. mirabilis is often found on indwelling urinary catheters causing monomicrobial and polymicrobial catheter-associated urinary tract infection (CAUTI). Widespread antibiotic resistance, combined with the ability of P. mirabilis to form urinary calculi during infection, warrants further investigation of this pathogen and its host interaction in an infection model that more closely mimics the presence of an indwelling urinary catheter. Here, we describe the methods necessary to establish a murine model of P. mirabilis CAUTI.

Blowing epithelial cell bubbles with GumB: ShlA-family pore-forming toxins induce blebbing and rapid cellular death in corneal epithelial cells.

Medical devices, such as contact lenses, bring bacteria in direct contact with human cells. Consequences of these host-pathogen interactions include the alteration of mammalian cell surface architecture and induction of cellular death that renders tissues more susceptible to infection. Gram-negative bacteria known to induce cellular blebbing by mammalian cells, Pseudomonas and Vibrio species, do so through a type III secretion system-dependent mechanism. This study demonstrates that a subset of bacteria from the Enterobacteriaceae bacterial family induce cellular death and membrane blebs in a variety of cell types via a type V secretion-system dependent mechanism. Here, we report that ShlA-family cytolysins from Proteus mirabilis and Serratia marcescens were required to induce membrane blebbling and cell death. Blebbing and cellular death were blocked by an antioxidant and RIP-1 and MLKL inhibitors, implicating necroptosis in the observed phenotypes. Additional genetic studies determined that an IgaA family stress-response protein, GumB, was necessary to induce blebs. Data supported a model where GumB and shlBA are in a regulatory circuit through the Rcs stress response phosphorelay system required for bleb formation and pathogenesis in an invertebrate model of infection and proliferation in a phagocytic cell line. This study introduces GumB as a regulator of S. marcescens host-pathogen interactions and demonstrates a common type V secretion system-dependent mechanism by which bacteria elicit surface morphological changes on mammalian cells. This type V secretion-system mechanism likely contributes bacterial damage to the corneal epithelial layer, and enables access to deeper parts of the tissue that are more susceptible to infection.

Necrotizing suppurative nephritis in a Japanese black feedlot steer due to Proteus mirabilis infection.

A Japanese black feedlot steer suddenly died after exhibiting astasia and cramping of the extremities. Necropsy of the animal revealed that the right kidney was enlarged and pale with severe nephrolithiasis. The urinary bladder displayed mucosal hemorrhage. Upon bacteriological investigation, Proteus mirabilis was isolated from the liver, spleen, right kidney, lungs and urine. Histopathological examination revealed necrotizing suppurative nephritis with the presence of numerous gram-negative bacilli and fibrinous suppurative cystitis with no bacilli. Immunohistochemical analysis revealed that the bacteria and cytoplasm of the macrophages stained positively with P. mirabilis antiserum. Electron microscopy revealed the presence of numerous bacteria in the renal tubules. To our knowledge, this is the first report describing the histopathological aspects of nephritis caused by P. mirabilis in cattle.

From Catheter to Kidney Stone: The Uropathogenic Lifestyle of Proteus mirabilis.

Proteus mirabilis is a model organism for urease-producing uropathogens. These diverse bacteria cause infection stones in the urinary tract and form crystalline biofilms on indwelling urinary catheters, frequently leading to polymicrobial infection. Recent work has elucidated how P. mirabilis causes all of these disease states. Particularly exciting is the discovery that this bacterium forms large clusters in the bladder lumen that are sites for stone formation. These clusters, and other steps of infection, require two virulence factors in particular: urease and MR/P fimbriae. Highlighting the importance of MR/P fimbriae is the cotranscribed regulator, MrpJ, which globally controls virulence. Overall, P. mirabilis exhibits an extraordinary lifestyle, and further probing will answer exciting basic microbiological and clinically relevant questions.

Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability.

We review the evidence that infectious agents, including those that become dormant within the host, have a major role to play in much of the etiology of rheumatoid arthritis and the inflammation that is its hallmark. This occurs in particular because they can produce cross-reactive (auto-)antigens, as well as potent inflammagens such as lipopolysaccharide that can themselves catalyze further inflammagenesis, including via ß-amyloid formation. A series of observables coexist in many chronic, inflammatory diseases as well as rheumatoid arthritis. They include iron dysregulation, hypercoagulability, anomalous morphologies of host erythrocytes, and microparticle formation. Iron dysregulation may be responsible for the periodic regrowth and resuscitation of the dormant bacteria, with concomitant inflammagen production. The present systems biology analysis benefits from the philosophical idea of "coherence," that reflects the principle that if a series of ostensibly unrelated findings are brought together into a self-consistent narrative, that narrative is thereby strengthened. As such, we provide a coherent and testable narrative for the major involvement of (often dormant) bacteria in rheumatoid arthritis.

Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation.

The catheter-associated uropathogenProteus mirabilisfrequently causes urinary stones, but little has been known about the initial stages of bladder colonization and stone formation. We found thatP. mirabilisrapidly invades the bladder urothelium, but generally fails to establish an intracellular niche. Instead, it forms extracellular clusters in the bladder lumen, which form foci of mineral deposition consistent with development of urinary stones. These clusters elicit a robust neutrophil response, and we present evidence of neutrophil extracellular trap generation during experimental urinary tract infection. We identified two virulence factors required for cluster development: urease, which is required for urolithiasis, and mannose-resistantProteus-like fimbriae. The extracellular cluster formation byP. mirabilisstands in direct contrast to uropathogenicEscherichia coli, which readily formed intracellular bacterial communities but not luminal clusters or urinary stones. We propose that extracellular clusters are a key mechanism ofP. mirabilissurvival and virulence in the bladder.

[АNTISEPTICS: MODERN STRATEGY OF STRUGGLE WITH CAUSING AGENTS OF THE ІNFECTION COMPLICATIONS].

Etiology of infective complications was investigated in 71 injured persons, suffering severe burns. There was established, that the main causing agents in patients, suffering burn disease, are S. aureus(in 35.9% of observations), A. baumannii (in 25%), P. aeruginosa (in 12.82%), P. mirabilis (in 5.12%). Resistance of conditionally pathogenic microorganisms towards cephalosporins, аminoglycosides, іmipenem, meropenem, doxycycline was determined. Effective bactericidal activity of antiseptic solutions of decasan, miramistinum, chlorhexidine was proved. High antimicrobial properties of dressing materials, which contain decametoxine, chlorhexidine, furagin, silver ions against Staphylococcus were noted. Clinical efficacy of application of materials, impregnated by antimicrobial composition decametoxine with carboxymethylstarch, oxyethylcellulose and polyvynilacetate, for prophylaxis and treatment of infective purulent­inflammatory complications in patients, suffering burns, was proved.

Proteus mirabilis and Urinary Tract Infections.

Proteus mirabilis is a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls'-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review covers P. mirabilis with a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming. P. mirabilis uses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and deciphering P. mirabilis pathogenesis.

GlpC gene is responsible for biofilm formation and defense against phagocytes and imparts tolerance to pH and organic solvents in Proteus vulgaris.

Biofilm-forming bacteria are highly resistant to antibiotics, host immune defenses, and other external conditions. The formation of biofilms plays a key role in colonization and infection. To explore the mechanism of biofilm formation, mutant strains of Proteus vulgaris XC 2 were generated by Tn5 random transposon insertion. Only one biofilm defective bacterial species was identified from among 500 mutants. Inactivation of the glpC gene coding an anaerobic glycerol-3-phosphate dehydrogenase subunit C was identified by sequence analysis of the biofilm defective strain. Differences were detected in the growth phenotypes of the wild-type and mutant strains under pH, antibiotic, and organic solvent stress conditions. Furthermore, we observed an increase in the phagocytosis of the biofilm defective strain by the mouse macrophage RAW264.7 cell line compared to the wild-type strain. This study shows that the glpC gene plays an important role in biofilm formation, in addition to imparting pH, organic solvent, and antibiotic tolerance, and defense against phagocytosis to Proteus sp. The results further clarified the mechanism of biofilm formation at the genomic level, and indicated the importance of the glpC gene in this process. This data may provide innovative therapeutic measures against P. vulgaris infections; furthermore, as an important crocodile pathogen, this study also has important significance in the protection of Chinese alligators.

Distinct Commensals Induce Interleukin-1ß via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury.

The microbiota stimulates inflammation, but the signaling pathways and the members of the microbiota involved remain poorly understood. We found that the microbiota induces interleukin-1ß (IL-1ß) release upon intestinal injury and that this is mediated via the NLRP3 inflammasome. Enterobacteriaceae and in particular the pathobiont Proteus mirabilis, induced robust IL-1ß release that was comparable to that induced by the pathogen Salmonella. Upon epithelial injury, production of IL-1ß in the intestine was largely mediated by intestinal Ly6C(high) monocytes, required chemokine receptor CCR2 and was abolished by deletion of IL-1ß in CCR2(+) blood monocytes. Furthermore, colonization with P. mirabilis promoted intestinal inflammation upon intestinal injury via the production of hemolysin, which required NLRP3 and IL-1 receptor signaling in vivo. Thus, upon intestinal injury, selective members of the microbiota stimulate newly recruited monocytes to induce NLRP3-dependent IL-1ß release, which promotes inflammation in the intestine.

New aspects of RpoE in uropathogenic Proteus mirabilis.

Proteus mirabilis is a common human pathogen causing recurrent or persistent urinary tract infections (UTIs). The underlying mechanisms for P. mirabilis to establish UTIs are not fully elucidated. In this study, we showed that loss of the sigma factor E (RpoE), mediating extracytoplasmic stress responses, decreased fimbria expression, survival in macrophages, cell invasion, and colonization in mice but increased the interleukin-8 (IL-8) expression of urothelial cells and swarming motility. This is the first study to demonstrate that RpoE modulated expression of MR/P fimbriae by regulating mrpI, a gene encoding a recombinase controlling the orientation of MR/P fimbria promoter. By real-time reverse transcription-PCR, we found that the IL-8 mRNA amount of urothelial cells was induced significantly by lipopolysaccharides extracted from rpoE mutant but not from the wild type. These RpoE-associated virulence factors should be coordinately expressed to enhance the fitness of P. mirabilis in the host, including the avoidance of immune attacks. Accordingly, rpoE mutant-infected mice displayed more immune cell infiltration in bladders and kidneys during early stages of infection, and the rpoE mutant had a dramatically impaired ability of colonization. Moreover, it is noteworthy that urea (the major component in urine) and polymyxin B (a cationic antimicrobial peptide) can induce expression of rpoE by the reporter assay, suggesting that RpoE might be activated in the urinary tract. Altogether, our results indicate that RpoE is important in sensing environmental cues of the urinary tract and subsequently triggering the expression of virulence factors, which are associated with the fitness of P. mirabilis, to build up a UTI.

An ultrastructural study, effects of Proteus vulgaris OX19 on the rabbit spleen cells.

Effects of Proteus vulgaris OX19 on the spleen cells of rabbits were investigated. Control group (n=5) and Proteus treated group (n=5) of New Zealand male rabbits were used in this study. Bacteria were injected to the rabbits in five days periods with increasing dosages for one month. Thin sections were examined by transmission electron microscope (Jeol 100CXII). Ultrastructural changes were defined in spleen tissue cells due to the antigenic stimulation of bacteria. Spleen cells observed in control group were in normal structure and cells were in close contact with each other. However, spleen cells of Proteus treated group displayed structural changes with regard to the control group in electron microscopic examinations. Chemotaxis of macrophages, forming of pseudopodia and presence of phagocytic vacuoles were observed. Lymphocytes, the major cells of spleen revealed mitotic activity. In addition, chromatin condensation in nucleus and dilatations in perinuclear space were significant. Interactions of lymphocytes and macrophages were noteworthy.

Spread of odontogenic infections in Port Harcourt, Nigeria.

PURPOSE: Odontogenic infections constitute a substantial portion of diseases encountered by oral and maxillofacial surgeons. Infections start from dental tissues and sometimes rapidly spread to contiguous spaces. The consequence is a fulminant disease with significant morbidity and mortality. The study was aimed at studying the pattern of spread, approach to management, and outcome of these infections at a Nigerian teaching hospital. PATIENTS AND METHODS: A retrospective study of all patients with orofacial infections who presented to our center over an 18-month period was carried out. The medical records were reviewed to retrieve the following: age, gender, source of infection, anatomic fascial spaces involved, associated medical conditions, various treatment modalities, types of antibiotics administered, causative micro-organisms, length of stay in the hospital, and any complications encountered. Infections were classified into 2 categories: those that are confined to the dentoalveolar tissues belong to category I, and those that have spread into the local/regional soft tissue spaces and beyond belong to category II. RESULTS: Odontogenic infections constituted 11.3% of the total oral and maxillofacial surgery cases. A total of 261 patients were treated for odontogenic infections. There were 146 female patients (59.8%) and 98 male patients (40.2%) in the first category, whereas the second category comprised 10 male patients (58.8%) and 7 female patients (41.2%). The fascial spaces involved, in descending order, were submasseteric in 10 (22.7%), submandibular in 9 (20.5%), and sublingual in 6 (13.6%). The causative micro-organisms commonly found were Klebsiella and Streptococcus spp. Incision and drainage were performed in the 17 cases with spreading infection. Amoxicillin, amoxicillin/clavulanate, and metronidazole were the most routinely administered antibiotics. CONCLUSIONS: Our experience shows that delay in presentation, self-medication, aging, male gender, and unusual causative agents are some of the factors associated with spread. Therefore efforts must be made to further improve public dental awareness.

Absceso cerebral como una complicación de otitis media supurada en adulto joven / Brain abscess as a complication of suppurative otitis media in a young man

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ZapA, a virulence factor in a rat model of Proteus mirabilis-induced acute and chronic prostatitis.

Our knowledge of pathogenesis has benefited from a better understanding of the roles of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in prostatitis, rats were infected with either wild-type (WT) P. mirabilis or its isogenic ZapA(-) mutant KW360. The WT produced both acute and chronic prostatitis showing the typical histological progressions that are the hallmarks of these diseases. Infection with the ZapA(-) mutant, however, resulted in reduced levels of acute prostatitis, as determined from lower levels of tissue damage, bacterial colonization, and inflammation. Further, the ZapA(-) mutant failed to establish a chronic infection, in that bacteria were cleared from the prostate, inflammation was resolved, and tissue was seen to be healing. Clearance from the prostate was not the result of a reduced capacity of the ZapA(-) mutant to form biofilms in vitro. These finding clearly define ZapA as an important virulence factor in both acute and chronic bacterial prostatitis.

Septic postpartum uterine inversion.

Puerperal uterine inversion is an uncommon but life threatening obstetrical emergency. A 26-year-old woman, para six, was referred from a peripheral hospital seven days after delivery, with a mass protruding per vaginum. Complete uterine inversion had occurred after delivery of baby and placenta. She was resuscitated and her genital infection was treated. She had a vaginal hysterectomy upon request. Her postoperative recovery was uneventful. Poor management of the third stage of labour is a common cause of uterine inversion. Early replacement of the inverted uterus is important to prevent further complications.

[Xanthogranulomatous pyelonephritis: presentation of an unusual case]. / Xanthogranulomatöse Pyelonephritis: Präsentation eines ungewöhnlichen Falles.

INTRODUCTION: Xanthogranulomatous pyelonephritis is a morphologically and clinically unique manifestation of chronic pyelonephritis with the formation of pus or granulomas. The most frequent predisposing factors for the development of xanthogranulomatous pyelonephritis are urinary obstruction (e. g., stones, tumors, congenital anomalies and functional impairment) and infection of the collecting system. CASE REPORT: We describe a 2-year-old female patient with unclear abdominal complaints, diarrhea, malaise, loss of appetite, weight loss, pale skin color, and recurrent and undulating fever in the presence of known left nephrolithiasis. Based on the clinical examination and imaging, above all, CT, the presumptive diagnosis of xanthogranulomatous pyelonephritis of the left kidney was made. A left lumbar nephrectomy was performed and histology confirmed the diagnosis. CONCLUSION: Xanthogranulomatous pyelonephritis is a relatively rare entity that is associated with obstruction (e. g., stones) and infection of the urinary tract. Its rarity and resultant unfamiliarity often delay diagnosis and therapy, which in turn affect the prognosis. Furthermore, this entity can be mistaken for renal tumors (renal cell carcinoma and Wilms tumor), but nowadays this should be mostly eliminated with the advances in the imaging methods.

[Bladder rupture caused by spontaneous perforation of an infected urachal cyst]. / Blasenruptur durch spontane Perforation einer infizierten Urachuszyste.

Anomalies of the fetal urachus are rare. Normally, the postnatal urachus presents as a fibrous band extending from the bladder to the umbilicus. Urachal cysts may occur in postnatal life. Spontaneous perforation of urachal cysts is a very rare condition, which clinically may not be distinguishable from other acute abdominal conditions. We report a case of a 63-year-old male with a history of recurrent urinary tract infections and a bladder rupture caused by a spontaneous perforation of an infected urachal cyst. The symptomatology showed abdominal rigidity and pain, a palpable mass in the lower abdomen, and hematuria. Laboratory findings showed leukocytosis and an increased CRP level. The bladder rupture was confirmed by cystography. Bacteriologic examination identified Proteus vulgaris, Corynebacterium species, and Klebsiella pneumoniae. Most of the published cases in the literature report about intraperitoneal perforation of infected urachal cysts. In the present case, we found a spontaneous perforation of an infected urachal cyst leading to an extraperitoneal bladder rupture with an extraperitoneal limitation of the infection. The definitive therapy was complete surgical excision including a cuff of the bladder, drainage, and systemic broad-spectrum and local application of antibiotics. The further course was uneventful.