scholarly journals A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage

2020 ◽  
Vol 16 (12) ◽  
pp. e1009192
Author(s):  
Jenna L. Sandala ◽  
Bradley W. Eichar ◽  
Laura G. Kuo ◽  
Mark M. Hahn ◽  
Akash K. Basak ◽  
...  
Keyword(s):  
Small Molecules ◽  
Dual Therapy ◽  
Biofilm Growth ◽  
Efficient Treatment ◽  
Therapy Approach ◽  
Log Reduction ◽  
Peripheral Organs ◽  
Asymptomatic Carriage ◽  
Bacterial Dissemination ◽  
Chronic Carriage

Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria from environmental insults and immune system clearance. Here, we identified two unique small molecules capable of both inhibiting Salmonella biofilm growth and disrupting pre-formed biofilm structures without affecting bacterial viability. In a mouse model of chronic gallbladder Salmonella carriage, treatment with either compound reduced bacterial burden in the gallbladder by 1–2 logs resulting in bacterial dissemination to peripheral organs that was associated with increased mortality. Co-administration of either compound with ciprofloxacin not only enhanced compound efficacy in the gallbladder by a further 1–1.5 logs for a total of 3–4.5 log reduction, but also prevented bacterial dissemination to peripheral organs. These data suggest a dual-therapy approach targeting both biofilm and planktonic populations can be further developed as a safe and efficient treatment of biofilm-mediated chronic S. Typhi infections.

Clinical Evaluation of AK 100 ULTRA for Predilution HF with on-line Prepared Bicarbonate Substitution Fluid. Comparison with HD and Acetate Postdilution HF

1997 ◽  
Vol 20 (3) ◽  
pp. 153-157
Author(s):  
D. Umido ◽  
P. Beretta ◽  
M.R. Vigano ◽  
P. Mariani ◽  
M. Borström ◽  
...  
Keyword(s):  
Small Molecules ◽  
Well Being ◽  
Good Alternative ◽  
Convective Transport ◽  
Treatment Modalities ◽  
Efficient Treatment ◽  
Long Time ◽  
On Line ◽  
Dialysis Membranes

Convective transport across dialysis membranes has been known for a long time to be a good alternative to diffusion. Predilution hemofiltration (HF) offers a better clearance of small molecules and overcomes the blood viscosity problems related to conventional postdilution HF treatment. Three patients have performed a total of 293 predilution HF treatment with AK 100 ULTRA. The bicarbonate substitution fluid has been prepared on-line by the machine. The treatments have been well tolerated and no adverse patients reactions related to the quality of the substitution fluid or the predilution HF treatment have been observed. There is a drop in creatinine for all patients indicating an improved creatinine clearance. Bicarbonate predilution HF has been shown to be a safe and efficient treatment modality, it offers the possibility to improve the cardiovascular stability of patients having problems with other treatment modalities an it offers an improved intertreatment well-being for the patients.

scholarly journals Filling the Void: An Optimized Polymicrobial Interkingdom Biofilm Model for Assessing Novel Antimicrobial Agents in Endodontic Infection

2020 ◽  
Vol 8 (12) ◽  
pp. 1988
Author(s):  
Sumaya Abusrewil ◽  
Jason L. Brown ◽  
Christopher D. Delaney ◽  
Mark C. Butcher ◽  
Ryan Kean ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Fusobacterium Nucleatum ◽  
Atmospheric Conditions ◽  
Candida Spp ◽  
Biofilm Growth ◽  
Log Reduction ◽  
Biofilm Model ◽  
Endodontic Infection ◽  
Endodontic Infections ◽  
Ontological Analysis

There is a growing realization that endodontic infections are often polymicrobial, and may contain Candida spp. Despite this understanding, the development of new endodontic irrigants and models of pathogenesis remains limited to mono-species biofilm models and is bacterially focused. The purpose of this study was to develop and optimize an interkingdom biofilm model of endodontic infection and use this to test suitable anti-biofilm actives. Biofilms containing Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, and Candida albicans were established from ontological analysis. Biofilms were optimized in different media and atmospheric conditions, prior to quantification and imaging, and subsequently treated with chlorhexidine, EDTA, and chitosan. These studies demonstrated that either media supplemented with serum were equally optimal for biofilm growth, which were dominated by S. gordonii, followed by C. albicans. Assessment of antimicrobial activity showed significant effectiveness of each antimicrobial, irrespective of serum. Chitosan was most effective (3 log reduction), and preferentially targeted C. albicans in both biofilm treatment and inhibition models. Chitosan was similarly effective at preventing biofilm growth on a dentine substrate. This study has shown that a reproducible and robust complex interkingdom model, which when tested with the antifungal chitosan, supports the notion of C. albicans as a key structural component.

scholarly journals Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant Staphylococcus aureus Strains

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 749
Author(s):  
Lei Wang ◽  
Tamta Tkhilaishvili ◽  
Andrej Trampuz
Keyword(s):  
Staphylococcus Aureus ◽  
Inhibitory Activity ◽  
Synergistic Effects ◽  
Laboratory Strain ◽  
Inhibitory Effect ◽  
Antimicrobial Treatment ◽  
Synergistic Activity ◽  
Biofilm Growth ◽  
Log Reduction ◽  
Suppressive Antibiotic Therapy

Effective antimicrobials are crucial for managing Staphylococcus aureus implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant S. aureus (RRSA). Failure to remove the implant results in persistent infection; thus, prolonged suppressive antibiotic therapy may be a reasonable alternative. However, a high incidence of adverse events can necessitate the discontinuation of therapy. In this scenario, commercial Staphylococcal bacteriophage Sb-1 combined with antibiotics is an option, showing a promising synergistic activity to facilitate the treatment of biofilm infections. Therefore, we evaluated the efficacy of the inhibitory activity of five antibiotics (doxycycline, levofloxacin, clindamycin, linezolid, and rifampin) alone or combined with phage Sb-1 (106 PFU/mL) in a simultaneous and staggered manner, to combat five clinical RRSA strains and the laboratory strain MRSA ATCC 43300 in 72 h by isothermal microcalorimetry. The synergistic effects were observed when phage Sb-1 (106 PFU/mL) combined with antibiotics had at least 2 log-reduction lower concentrations, represented by a fractional biofilm inhibitory concentration (FBIC) of <0.25. Among the antibiotics that we tested, the synergistic effect of all six strains was achieved in phage/doxycycline and phage/linezolid combinations in a staggered manner, whereas a distinctly noticeable improvement in inhibitory activity was observed in the phage/doxycycline combination with a low concentration of doxycycline. Moreover, phage/levofloxacin and phage/clindamycin combinations also showed a synergistic inhibitory effect against five strains and four strains, respectively. Interestingly, the synergistic inhibitory activity was also observed in the doxycycline-resistant and levofloxacin-resistant profile strains. However, no inhibitory activity was observed for all of the combinations in a simultaneous manner, as well as for the phage/rifampin combination in a staggered manner. These results have implications for alternative, combined, and prolonged suppressive antimicrobial treatment approaches.

scholarly journals OligoG CF-5/20 Disruption of Mucoid Pseudomonas aeruginosa Biofilm in a Murine Lung Infection Model

2016 ◽  
Vol 60 (5) ◽  
pp. 2620-2626 ◽  
Author(s):  
Wang Hengzhuang ◽  
Zhijun Song ◽  
Oana Ciofu ◽  
Edvar Onsøyen ◽  
Philip D. Rye ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Infection Model ◽  
Dependent Manner ◽  
Clinical Value ◽  
Biofilm Growth ◽  
Content Type ◽  
Log Reduction

ABSTRACTBiofilm growth is a universal survival strategy for bacteria, providing an effective and resilient approach for survival in an otherwise hostile environment. In the context of an infection, a biofilm provides resistance and tolerance to host immune defenses and antibiotics, allowing the biofilm population to survive and thrive under conditions that would destroy their planktonic counterparts. Therefore, the disruption of the biofilm is a key step in eradicating persistent bacterial infections, as seen in many types of chronic disease. In these studies, we used bothin vitrominimum biofilm eradication concentration (MBEC) assays and anin vivomodel of chronic biofilm infection to demonstrate the biofilm-disrupting effects of an alginate oligomer, OligoG CF-5/20. Biofilm infections were established in mice by tracheal instillation of a mucoid clinical isolate ofPseudomonas aeruginosaembedded in alginate polymer beads. The disruption of the biofilm by OligoG CF-5/20 was observed in a dose-dependent manner over 24 h, with up to a 2.5-log reduction in CFU in the infected mouse lungs. Furthermore,in vitroassays showed that 5% OligoG CF-5/20 significantly reduced the MBEC for colistin from 512 μg/ml to 4 μg/ml after 8 h. These findings support the potential for OligoG CF-5/20 as a biofilm disruption agent which may have clinical value in reducing the microbial burden in chronic biofilm infections.

scholarly journals Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Erik van Tilburg Bernardes ◽  
Laetitia Charron-Mazenod ◽  
David J. Reading ◽  
Shauna L. Reckseidler-Zenteno ◽  
Shawn Lewenza
Keyword(s):  
Extracellular Matrix ◽  
Pseudomonas Aeruginosa ◽  
Small Molecules ◽  
Biofilm Formation ◽  
Flow Chamber ◽  
Growth Strategy ◽  
Antibiofilm Activity ◽  
Biofilm Growth ◽  
Content Type ◽  
High Throughput Gene Expression

ABSTRACT Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. Pseudomonas aeruginosa is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of P. aeruginosa biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of P. aeruginosa produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the pel genes. The pel repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence, pel/psl mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in Caenorhabditis elegans. The antibiofilm molecules also reduced P. aeruginosa PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of P. aeruginosa biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic P. aeruginosa infections.

Enhancing plant productivity while suppressing biofilm growth in a windowfarm system using beneficial bacteria and ultraviolet irradiation

2015 ◽  
Vol 61 (7) ◽  
pp. 457-466 ◽  
Author(s):  
Seungjun Lee ◽  
Chongtao Ge ◽  
Zuzana Bohrerova ◽  
Parwinder S. Grewal ◽  
Jiyoung Lee
Keyword(s):  
Uv Irradiation ◽  
Water Reservoir ◽  
Pythium Ultimum ◽  
Pseudomonas Chlororaphis ◽  
Biofilm Growth ◽  
Hydroponic System ◽  
Log Reduction ◽  
System A ◽  
Number Of Leaves ◽  
Better Than

Common problems in a windowfarm system (a vertical and indoor hydroponic system) are phytopathogen infections in plants and excessive buildup of biofilms. The objectives of this study were (i) to promote plant health by making plants more resistant to infection by using beneficial biosurfactant-producing Pseudomonas chlororaphis around the roots and (ii) to minimize biofilm buildup by ultraviolet (UV) irradiation of the water reservoir, thereby extending the lifespan of the whole system with minimal maintenance. Pseudomonas chlororaphis-treated lettuce grew significantly better than nontreated lettuce, as indicated by enhancement of color, mass, length, and number of leaves per head (p < 0.05). The death rate of the lettuce was reduced by ∼50% when the lettuce was treated with P. chlororaphis. UV irradiation reduced the bacteria (4 log reduction) and algae (4 log reduction) in the water reservoirs and water tubing systems. Introduction of P. chlororaphis into the system promoted plant growth and reduced damage caused by the plant pathogen Pythium ultimum. UV irradiation of the water reservoir reduced algal and biofilm growth and extended the lifespan of the system.

Gap junctions in the prothoracic glands of the tobacco hornworm, Manduca sexta

1992 ◽  
Vol 50 (1) ◽  
pp. 706-707
Author(s):  
Ji-da Dai ◽  
M. Joseph Costello ◽  
Lawrence I. Gilbert
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
Manduca Sexta ◽  
Freeze Fracture ◽  
Cell Communication ◽  
Cellular Level ◽  
Thin Sections ◽  
Prothoracic Glands ◽  
Polyhydroxylated Steroids ◽  
Stimulation Of

Insect molting and metamorphosis are elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands (PGs). Prothoracicotropic hormone stimulation of steroidogenesis by the PGs at the cellular level involves both calcium and cAMP. Cell-to-cell communication mediated by gap junctions may play a key role in regulating signal transduction by controlling the transmission of small molecules and ions between adjacent cells. This is the first report of gap junctions in the PGs, the evidence obtained by means of SEM, thin sections and freeze-fracture replicas.

Sign in / Sign up

Export Citation Format

Share Document