Short FtsZ filaments can drive asymmetric cell envelope constriction at the onset of bacterial cytokinesis.

FtsZ, the bacterial homologue of eukaryotic tubulin, plays a central role in cell division in nearly all bacteria and many archaea. It forms filaments under the cytoplasmic membrane at the division site where, together with other proteins it recruits, it drives peptidoglycan synthesis and constricts the cell. Despite extensive study, the arrangement of FtsZ filaments and their role in division continue to be debated. Here, we apply electron cryotomography to image the native structure of intact dividing cells and show that constriction in a variety of Gram-negative bacterial cells, including Proteus mirabilis and Caulobacter crescentus, initiates asymmetrically, accompanied by asymmetric peptidoglycan incorporation and short FtsZ-like filament formation. These results show that a complete ring of FtsZ is not required for constriction and lead us to propose a model for FtsZ-driven division in which short dynamic FtsZ filaments can drive initial peptidoglycan synthesis and envelope constriction at the onset of cytokinesis, later increasing in length and number to encircle the division plane and complete constriction.

Twin arginine translocation, ammonia incorporation, and polyamine biosynthesis are crucial for Proteus mirabilis fitness during bloodstream infection.

The Gram-negative bacterium Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTI), which can progress to secondary bacteremia. While numerous studies have investigated experimental infection with P. mirabilis in the urinary tract, little is known about pathogenesis in the bloodstream. This study identifies the genes that are important for survival in the bloodstream using a whole-genome transposon insertion-site sequencing (Tn-Seq) approach. A library of 50,000 transposon mutants was utilized to assess the relative contribution of each non-essential gene in the P. mirabilis HI4320 genome to fitness in the livers and spleens of mice at 24 hours following tail vein inoculation compared to growth in RPMI, heat-inactivated (HI) naïve serum, and HI acute phase serum. 138 genes were identified as ex vivo fitness factors in serum, which were primarily involved in amino acid transport and metabolism, and 143 genes were identified as infection-specific in vivo fitness factors for both spleen and liver colonization. Infection-specific fitness factors included genes involved in twin arginine translocation, ammonia incorporation, and polyamine biosynthesis. Mutants in sixteen genes were constructed to validate both the ex vivo and in vivo results of the transposon screen, and 12/16 (75%) exhibited the predicted phenotype. Our studies indicate a role for the twin arginine translocation (tatAC) system in motility, translocation of potential virulence factors, and fitness within the bloodstream. We also demonstrate the interplay between two nitrogen assimilation pathways in the bloodstream, providing evidence that the GS-GOGAT system may be preferentially utilized. Furthermore, we show that a dual-function arginine decarboxylase (speA) is important for fitness within the bloodstream due to its role in putrescine biosynthesis rather than its contribution to maintenance of membrane potential. This study therefore provides insight into pathways needed for fitness within the bloodstream, which may guide strategies to reduce bacteremia-associated mortality.

Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections-An In Vitro and In Silico Perspective.

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19-0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.

Impact of Antibiotic-Resistant Bacteria on Immune Activation and Clostridioides difficile Infection in the Mouse Intestine.

Antibiotic treatment of patients undergoing complex medical treatments can deplete commensal bacterial strains from the intestinal microbiota, thereby reducing colonization resistance against a wide range of antibiotic-resistant pathogens. Loss of colonization resistance can lead to marked expansion of vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae, and Escherichia coli in the intestinal lumen, predisposing patients to bloodstream invasion and sepsis. The impact of intestinal domination by these antibiotic-resistant pathogens on mucosal immune defenses and epithelial and mucin-mediated barrier integrity is unclear. We used a mouse model to study the impact of intestinal domination by antibiotic-resistant bacterial species and strains on the colonic mucosa. Intestinal colonization with K. pneumoniae, Proteus mirabilis, or Enterobacter cloacae promoted greater recruitment of neutrophils to the colonic mucosa. To test the hypothesis that the residual microbiota influences the severity of colitis caused by infection with Clostridioides difficile, we coinfected mice that were colonized with ampicillin-resistant bacteria with a virulent strain of C. difficile and monitored colonization and pathogenesis. Despite the compositional differences in the gut microbiota, the severity of C. difficile infection (CDI) and mortality did not differ significantly between mice colonized with different ampicillin-resistant bacterial species. Our results suggest that the virulence mechanisms enabling CDI and epithelial destruction outweigh the relatively minor impact of less-virulent antibiotic-resistant intestinal bacteria on the outcome of CDI.

Inhibition of urease activity in the urinary tract pathogens Staphylococcus saprophyticus and Proteus mirabilis by dimethylsulfoxide (DMSO).

AIMS: Urease is a virulence factor for the urinary tract pathogens Staphylococcus saprophyticus and Proteus mirabilis. Dimethylsulfoxide (DMSO) is structurally similar to urea, used as a solvent for urease inhibitors, and an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS). The aims of this study were to test DMSO as a urease inhibitor and determine its physiological effects on S. saprophyticus and P. mirabilis. METHODS AND RESULTS: Urease activity in extracts and whole cells was measured by the formation of ammonium ions. Urease was highly sensitive to noncompetitive inhibition by DMSO (Ki about 6 mmol l-1 ). DMSO inhibited urease activity in whole cells, limited bacterial growth in media containing urea, and slowed the increase in pH which occurred in artificial urine medium. CONCLUSIONS: DMSO should be used with caution as a solvent when testing plant extracts or other potential urease inhibitors. Because it can inhibit bacterial growth and delay an increase in pH, it may be an effective treatment for urinary tract infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first detailed study of the inhibition of urease by DMSO. Dimethylsulfoxide may be used to treat urinary tract infections that are resistant to antibiotics or herbal remedies.

Phytochemical, antimicrobial and time-kill kinetics potentials of Euphorbia nivulia Buch.-Ham.: A Cholistan desert medicinal plant.

Euphorbia nivulia a locally occurring plant species possesses antiseptic, analgesic and anti-inflammatory properties and is ethnopharmacologically used in various ailments like skin, ear disorders, boils, and worm infestation. Preliminary phytochemical screening showed presence of flavonoids, polyphenolics, glycosides, alkaloids, tannins and triterpenoids in (70% aqueous-ethanolic) Euphorbia nivulia crude extract (En cr) and its four fractions, i.e., hexane fraction (En hex), butanol fraction (En bt), chloroform fraction (En ch), and aqueous fraction (En aq). In current study, Agar well diffusion and time-kill kinetic assays were performed for antimicrobial activity. 300 mg/ml concentration showed maximum inhibitory zone. Highest zone of inhibition (15.5mm) was demonstrated by En ch fraction against Proteus mirabilis. Staphyllococcus aureus was the most sensitive bacteria against whom all fractions except En aq fraction were active. Maximum MIC (15.3 mg/ml) was shown by En ch fraction against Proteus mirabilis. Similarly, En ch fraction showed (15.1 mg/ml) remarkable MIC against Candida albicans. Significant higher antibacterial and antifungal activity was revealed in high concentration. Time-kill kinetics studies revealed bacteriostatic action. Noteworthy antimicrobial activity may be due to bioactive compounds of extract which may be a potential antibacterial and antifungal agent.

A Rare Opportunist, Morganella morganii, Decreases Severity of Polymicrobial Catheter-Associated Urinary Tract Infection.

Catheter-associated urinary tract infections (CAUTIs) are common hospital-acquired infections and frequently polymicrobial, which complicates effective treatment. However, few studies experimentally address the consequences of polymicrobial interactions within the urinary tract, and the clinical significance of polymicrobial bacteriuria is not fully understood. Proteus mirabilis is one of the most common causes of monomicrobial and polymicrobial CAUTI and frequently cocolonizes with Enterococcus faecalis, Escherichia coli, Providencia stuartii, and Morganella morganiiP. mirabilis infections are particularly challenging due to its potent urease enzyme, which facilitates formation of struvite crystals, catheter encrustation, blockage, and formation of urinary stones. We previously determined that interactions between P. mirabilis and other uropathogens can enhance P. mirabilis urease activity, resulting in greater disease severity during experimental polymicrobial infection. Our present work reveals that M. morganii acts on P. mirabilis in a contact-independent manner to decrease urease activity. Furthermore, M. morganii actively prevents urease enhancement by E. faecalis, P. stuartii, and E. coli Importantly, these interactions translate to modulation of disease severity during experimental CAUTI, predominantly through a urease-dependent mechanism. Thus, products secreted by multiple bacterial species in the milieu of the catheterized urinary tract can directly impact prognosis.

Allicin prevents the formation of Proteus-induced urinary crystals and the blockage of catheter in a bladder model in vitro.

Stone formation and catheter blockage are major complications of Proteus UTIs. In this study, we investigated the ability of allicin to inhibit P. mirabilis-induced struvite crystallization and catheter blockage using a synthetic bladder model. Struvite crystallization inhibition study was carried out using P. mirabilis lysate as urease enzyme source in synthetic urine (SU). Struvite productions were monitored by phase contrast light microscopy and measurements of pH, Mg2+ and Ca2+ precipitation and turbidity. A catheter blockage study was performed in a synthetic bladder model mimicking natural UTI in the presence of allicin at sub-MIC concentrations (MIC = 64 µg/ml). The results of crystallization study showed that allicin inhibited pH rise and consequently turbidity and precipitation of ions in a dose-dependent manner. The results of catheter blockage study showed that allicin at sub-MIC concentrations (2, 4, 8 µg/ml) significantly increased the time for catheter blockage to occur to 61, 74 and 92 h respectively compared to allicin-free control (48 h). In a similar way, the results showed that allicin delayed the increase of SU pH level in bladder model in a dose-dependent manner compared to allicin-free control. The results also showed that following the increase of allicin concentration, Mg2+ and Ca2+ deposition in catheters were much lower compared to allicin-free control, further confirmed by direct observation of the catheters' eyehole and cross sections. We conclude that allicin prevents the formation of Proteus-induced urinary crystals and the blockage of catheters by delaying pH increase and lowering Mg2+ and Ca2+ deposition in a dose-dependent manner.

Bacterial biofilm formation on indwelling urethral catheters.

Urethral catheters are the most commonly deployed medical devices and used to manage a wide range of conditions in both hospital and community care settings. The use of long-term catheterization, where the catheter remains in place for a period >28 days remains common, and the care of these patients is often undermined by the acquisition of infections and formation of biofilms on catheter surfaces. Particular problems arise from colonization with urease-producing species such as Proteus mirabilis, which form unusual crystalline biofilms that encrust catheter surfaces and block urine flow. Encrustation and blockage often lead to a range of serious clinical complications and emergency hospital referrals in long-term catheterized patients. Here we review current understanding of bacterial biofilm formation on urethral catheters, with a focus on crystalline biofilm formation by P. mirabilis, as well as approaches that may be used to control biofilm formation on these devices. SIGNIFICANCE AND IMPACT OF THE STUDY: Urinary catheters are the most commonly used medical devices in many healthcare systems, but their use predisposes to infection and provide ideal conditions for bacterial biofilm formation. Patients managed by long-term urethral catheterization are particularly vulnerable to biofilm-related infections, with crystalline biofilm formation by urease producing species frequently leading to catheter blockage and other serious clinical complications. This review considers current knowledge regarding biofilm formation on urethral catheters, and possible strategies for their control.

Identification of small molecule compounds active against Staphylococcus aureus and Proteus mirabilis.

Staphylococcus aureus is a human pathogen rapidly becoming a serious health problem due to ease of acquiring antibiotic resistance. To help identify potential new drug candidates effective against the pathogen, a small focused library was screened for inhibition of bacterial growth against several pathogens, including S. aureus. At least one of the compounds, Compound 10, was capable of blocking bacterial growth of S. aureus in a test tube with IC50 = 140 ±â€¯30 µM. Another inhibitor, Compound 7, was bacteriostatic against S. aureus with IC50 ranging from 33 to 150 µM against 3 different strains. However, only Compound 7 was bactericidal against P. mirabilis as examined by electron microscopy. Human cell line toxicity studies suggested that both compounds had small effect on cell growth at 100 µM concentration as examined by MTT assay. Analysis of compounds' structures showed lack of similarity to any known antibiotics and bacteriostatics, potentially offering the inhibitors as an alternative to existing solutions in controlling bacterial infections for selected pathogens.

Changes in the lipopolysaccharide of Proteus mirabilis 9B-m (O11a) clinical strain in response to planktonic or biofilm type of growth.

The impact of planktonic and biofilm lifestyles of the clinical isolate Proteus mirabilis 9B-m on its lipopolysaccharide (O-polysaccharide, core region, and lipid A) was evaluated. Proteus mirabilis bacteria are able to form biofilm and lipopolysaccharide is one of the factors involved in the biofilm formation. Lipopolysaccharide was isolated from planktonic and biofilm cells of the investigated strain and analyzed by SDS-PAGE with silver staining, Western blotting and ELISA, as well as NMR and matrix-assisted laser desorption ionization time-of-flight mass spectrometry techniques. Chemical and NMR spectroscopic analyses revealed that the structure of the O-polysaccharide of P. mirabilis 9B-m strain did not depend on the form of cell growth, but the full-length chains of the O-antigen were reduced when bacteria grew in biofilm. The study also revealed structural modifications of the core region in the lipopolysaccharide of biofilm-associated cells-peaks assigned to compounds absent in cells from the planktonic culture and not previously detected in any of the known Proteus core oligosaccharides. No differences in the lipid A structure were observed. In summary, our study demonstrated for the first time that changes in the lifestyle of P. mirabilis bacteria leads to the modifications of their important virulence factor-lipopolysaccharide.

Activity of Salvia dolomitica and Salvia somalensis Essential Oils against Bacteria, Molds and Yeasts.

Essential oils (EOs) from Salvia dolomitica and Salvia somalensis, widely employed in the cosmetic and perfume industry, were analyzed for composition and tested against bacterial and fungal pathogens isolated from clinical and environmental specimens. The analyses were carried out against Staphylococcus aureus, Staphylococcus pseudointermedius, Pseudomonas aeruginosa, Escherichia coli, Streptococcus canis, Streptococcus pyogenes, Klebsiella pneumoniae, Proteus mirabilis, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Aspergillus niger, Aspergillus flavus, Candida albicans, Candida krusei, Mucor sp. and Trichothecium roseum. Both EOs showed similar percentages of total monoterpenes and sesquiterpene hydrocarbons. The main constituents were 1,8-cineole and ß-caryophyllene in S. dolomitica and bornyl acetate and camphor in S. somalensis. The selected EOs have no relevant antifungal or antibacterial activities if compared to conventional drugs.

Method for Bacterial Growth and Ammonia Production and Effect of Inhibitory Substances in Disposable Absorbent Hygiene Products.

PURPOSE: The purpose of this study was to evaluate a pragmatic laboratory method to provide a technique for developing incontinence products better able to reduce malodor when used in the clinical setting. METHODS: Bacterial growth and bacterially formed ammonia in disposable absorbent incontinence products was measured by adding synthetic urine inoculated with bacteria to test samples cut from the crotch area of the product. The inhibitory effect's of low pH (4.5 and 4.9) and 3 antimicrobial substances-chlorhexidine, polyhexamethylene biguanide (PHMB), and thymol-at 2 concentrations each, were studied. RESULTS: From the initial inocula of 3.3 log colony-forming units per milliliter (cfu/mL) at baseline, the bacterial growth of the references increased to 5.0 to 6.0 log cfu/mL at 6 hours for Escherichia coli, Proteus mirabilis, and Enterococcus faecalis. At 12 hours there was a further increase to 7.0 to 8.9 log cfu/mL. Adjusting the pH of the superabsorbent in the incontinence product from 6.0 to pH 4.5 and pH 4.9 significantly (P < .05) inhibited the bacterial growth rates, in most cases, both at 6 and 12 hours. The effect was most pronounced at pH 4.5. Chlorhexidine had significant (P < .05) inhibitory effect on E. coli and E. faecalis, and at 12 hours also on P. mirabilis. For PHMB and thymol the results varied. At 6 hours, the ammonia concentration in the references (pH 6.0) was 200 to 300 ppm and it was 1500 to 1600 ppm at 8 hours. At pH 4.5, no or little ammonia production was measured at 6 and 8 hours. At pH 4.9, there was a significant reduction (P < .01). Chlorhexidine and PHMB exerted a significant (P < .01 or P < .001) inhibitory effect on ammonia production at both concentrations and at 6 and 8 hours. Thymol 0.003% and 0.03% showed inhibitory effect at both 6 hours (P < .01 or P < .001) and at 8 hours (P < .05 or P < .001). CONCLUSION: The method described in this study can be used to compare the ability of various disposable absorbent products to inhibit bacterial growth and ammonia production. This technique, we describe, provides a pragmatic method for assessing the odor-inhibiting capacity of specific incontinence products.

The Self-Identity Protein IdsD Is Communicated between Cells in Swarming Proteus mirabilis Colonies.

Proteus mirabilis is a social bacterium that is capable of self (kin) versus nonself recognition. Swarming colonies of this bacterium expand outward on surfaces to centimeter-scale distances due to the collective motility of individual cells. Colonies of genetically distinct populations remain separate, while those of identical populations merge. Ids proteins are essential for this recognition behavior. Two of these proteins, IdsD and IdsE, encode identity information for each strain. These two proteins bind in vitro in an allele-restrictive manner. IdsD-IdsE binding is correlated with the merging of populations, whereas a lack of binding is correlated with the separation of populations. Key questions remained about the in vivo interactions of IdsD and IdsE, specifically, whether IdsD and IdsE bind within single cells or whether IdsD-IdsE interactions occur across neighboring cells and, if so, which of the two proteins is exchanged. Here we demonstrate that IdsD must originate from another cell to communicate identity and that this nonresident IdsD interacts with IdsE resident in the recipient cell. Furthermore, we show that unbound IdsD in recipient cells does not cause cell death and instead appears to contribute to a restriction in the expansion radius of the swarming colony. We conclude that P. mirabilis communicates IdsD between neighboring cells for nonlethal kin recognition, which suggests that the Ids proteins constitute a type of cell-cell communication. IMPORTANCE: We demonstrate that self (kin) versus nonself recognition in P. mirabilis entails the cell-cell communication of an identity-encoding protein that is exported from one cell and received by another. We further show that this intercellular exchange affects swarm colony expansion in a nonlethal manner, which adds social communication to the list of potential swarm-related regulatory factors.

Anaerobic choline metabolism in microcompartments promotes growth and swarming of Proteus mirabilis.

Gammaproteobacteria are important gut microbes but only persist at low levels in the healthy gut. The ecology of Gammaproteobacteria in the gut environment is poorly understood. Here, we demonstrate that choline is an important growth substrate for representatives of Gammaproteobacteria. Using Proteus mirabilis as a model, we investigate the role of choline metabolism and demonstrate that the cutC gene, encoding a choline-trimethylamine lyase, is essential for choline degradation to trimethylamine by targeted mutagenesis of cutC and subsequent complementation experiments. Proteus mirabilis can rapidly utilize choline to enhance growth rate and cell yield in broth culture. Importantly, choline also enhances swarming-associated colony expansion of P. mirabilis under anaerobic conditions on a solid surface. Comparative transcriptomics demonstrated that choline not only induces choline-trimethylamine lyase but also genes encoding shell proteins for the formation of bacterial microcompartments. Subsequent analyses by transmission electron microscopy confirmed the presence of such novel microcompartments in cells cultivated in liquid broth and hyper-flagellated swarmer cells from solid medium. Together, our study reveals choline metabolism as an adaptation strategy for P. mirabilis and contributes to better understand the ecology of this bacterium in health and disease.

The role of Proteus mirabilis cell wall features in biofilm formation.

Biofilms formed by Proteus mirabilis strains are a serious medical problem, especially in the case of urinary tract infections. Early stages of biofilm formation, such as reversible and irreversible adhesion, are essential for bacteria to form biofilm and avoid eradication by antibiotic therapy. Adhesion to solid surfaces is a complex process where numerous factors play a role, where hydrophobic and electrostatic interactions with solid surface seem to be substantial. Cell surface hydrophobicity and electrokinetic potential of bacterial cells depend on their surface composition and structure, where lipopolysaccharide, in Gram-negative bacteria, is prevailing. Our studies focused on clinical and laboratory P. mirabilis strains, where laboratory strains have determined LPS structures. Adherence and biofilm formation tests revealed significant differences between strains adhered in early stages of biofilm formation. Amounts of formed biofilm were expressed by the absorption of crystal violet. Higher biofilm amounts were formed by the strains with more negative values of zeta potential. In contrast, high cell surface hydrophobicity correlated with low biofilm amount.

Cranberry derivatives enhance biofilm formation and transiently impair swarming motility of the uropathogen Proteus mirabilis HI4320.

Proteus mirabilis is a major cause of catheter-associated urinary tract infection (CAUTI), emphasizing that novel strategies for targeting this bacterium are needed. Potential targets are P. mirabilis surface-associated swarming motility and the propensity of these bacteria to form biofilms that may lead to catheter blockage. We previously showed that the addition of cranberry powder (CP) to lysogeny broth (LB) medium resulted in impaired P. mirabilis swarming motility over short time periods (up to 16 h). Herein, we significantly expanded on those findings by exploring (i) the effects of cranberry derivatives on biofilm formation of P. mirabilis, (ii) whether swarming inhibition occurred transiently or over longer periods more relevant to real infections (∼3 days), (iii) whether swarming was also blocked by commercially available cranberry juices, (iv) whether CP or cranberry juices exhibited effects under natural urine conditions, and (v) the effects of cranberry on medium pH, which is an indirect indicator of urease activity. At short time scales (24 h), CP and commercially available pure cranberry juice impaired swarming motility and repelled actively swarming bacteria in LB medium. Over longer time periods more representative of infections (∼3 days), the capacity of the cranberry material to impair swarming diminished and bacteria would start to migrate across the surface, albeit by exhibiting a different motility phenotype to the regular "bull's-eye" swarming phenotype of P. mirabilis. This bacterium did not swarm on urine agar or LB agar supplemented with urea, suggesting that any potential application of anti-swarming compounds may be better suited to settings external to the urine environment. Anti-swarming effects were confounded by the ability of cranberry products to enhance biofilm formation in both LB and urine conditions. These findings provide key insights into the long-term strategy of targeting P. mirabilis CAUTIs.

[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.

Inhibitory effects of Lactobacillus fermentum on microbial growth and biofilm formation.

Beneficial effects of Lactobacilli have been reported, and lactic bacteria are employed for conservation of foods. Therefore, the effects of a Lactobacillus fermentum strain were analyzed regarding inhibitory effects on staphylococci, Candida albicans and enterotoxigenic enterobacteria by transmission electron microscopy (TEM). TEM of bacterial biofilms was performed using cocultures of bacteriocin-producing L. fermentum 97 with different enterotoxigenic strains: Staphylococcus epidermidis expressing the ica gene responsible for biofilm formation, Staphylococcus aureus producing enterotoxin type A, Citrobacter freundii, Enterobacter cloaceae, Klebsiella oxytoca, Proteus mirabilis producing thermolabile and thermostable enterotoxins determined by elt or est genes, and Candida albicans. L. fermentum 97 changed morphological features and suppressed biofilm formation of staphylococci, enterotoxigenic enterobacteria and Candida albicans; a marked transition to resting states, a degradation of the cell walls and cytoplasm, and a disruption of mature bacterial biofilms were observed, the latter indicating efficiency even in the phase of higher cell density.

Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data.