Large volume of wastewater consisting complex forms of organics, lipids and nutrients, is discharged from the abattoir (red meat) processing industry. In this study, nutrient rich pre-Anaerobic ...Membrane Bioreactor (AnMBR) treated abattoir effluent was fed to a struvite (MgNH4PO4.6H2O) precipitator to evaluate the possibility of developing an innovative environmentally sustainable treatment technology to produce nutrient free high-quality treated effluent. A series of continuous and batch experiments were conducted to investigate the influence of pH and presence of Ca2+ on struvite precipitation. The study found that Mg2+:Ca2+ molar ratio of 0.8 (or high Ca2+) impacts on the production and quality of struvite significantly. Pre-AnMBR treated abattoir wastewater with negligible Ca2+ (Mg2+:Ca2+ molar ratio > 20) showed over 80% removal of phosphorus via struvite precipitation. The highest removal rates of both nitrogen and phosphorus were achieved at pH 9.5 with Mg2+:PO43− molar ratio of 2:1.
•Struvite precipitation is a promising strategy to remove nutrients from wastewater.•High Ca2+ in effluent deteriorates the purity and production of struvite.•Both pH and Mg2+ dosing rate have a significant impact on nutrient recovery.•Chemical mixing time less than 3 h gave the highest removal of PO4–P.
Pressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant ...bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin's in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (10
CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log
reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log
reduction) and oral clindamycin (1.24-log
reduction), which are used to treat infected PUs clinically. The present study highlights auranofin's potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to ...current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant S. aureus (VRSA) clinical isolates. In addition, the anti-biofilm activity of the novel thiazoles was investigated against S. epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to resensitize VRSA to vancomycin, reducing its MIC by 512-fold in two strains. In addition, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively, the results obtained demonstrate that compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm.
•Auranofin is a potent inhibitor of Clostridium difficile growth•Auranofin, not vancomycin or metronidazole, blocked C. difficile toxin production•Auranofin also inhibited C. difficile spore ...formation•Auranofin protected gut cells against the effect of C. difficile toxins in vitro•Auranofin halted vancomycin-resistant enterococci more than anticlostridial drugs.
Clostridium difficile is a deadly, opportunistic bacterial pathogen. In the last two decades, C. difficile infections (CDIs) have become a national concern because of the emergence of hypervirulent mutants with increased capability to produce toxins and spores. This has resulted in an increased number of infections and deaths associated with CDI. The scarcity of anticlostridial drugs has led to unsatisfactory cure rates, elevated recurrence rates and permitted enhanced colonization with other drug-resistant pathogens (such as vancomycin-resistant enterococci) in afflicted patients. Therefore, both patients and physicians are facing an urgent need for more effective therapies to treat CDI. In an effort to find new anticlostridial drugs, we investigated auranofin, an FDA-approved oral antirheumatic drug that has recently been found to possess antibacterial activity. Auranofin exhibited potent activity against C. difficile isolates, inhibiting growth at a concentration of 1 µg/mL against 50% of all tested isolates. Auranofin inhibited both toxin production and spore formation, a property lacking in both vancomycin and metronidazole (the primary agents used to treat CDI). Auranofin had a direct protective activity against C. difficile toxin-mediated inflammation and inhibited the growth of vancomycin-resistant enterococci. Auranofin is a promising candidate that warrants further investigation as a treatment option for C. difficile infections.
Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. ...To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag) were taken up by macrophages, but not by non-phagocytic cells, such as fibroblasts, reducing non-specific toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexiganan-loaded NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection.
An experimental study was carried out to understand the electrical percolation thresholds of different carbon-based nano- and micro-scale materials in cementitious composites. Multi-walled carbon ...nanotubes (CNTs), graphene nanoplatelets (GNPs) and carbon black (CB) were selected as the nano-scale materials, while 6 and 12 mm long carbon fibers (CF6 and CF12) were used as the micro-scale carbon-based materials. After determining the percolation thresholds of different electrical conductive materials, mechanical properties and piezoresistive properties of specimens produced with the abovementioned conductive materials at percolation threshold were investigated under uniaxial compressive loading. Results demonstrate that regardless of initial curing age, the percolation thresholds of CNT, GNP, CB and CFs in ECC mortar specimens were around 0.55%, 2.00%, 2.00% and 1.00%, respectively. Including different carbon-based conductive materials did not harm compressive strength results; on the contrary, it improved overall values. All cementitious composites produced with carbon-based materials, with the exception of the control mixtures, exhibited piezoresistive behavior under compression, which is crucial for sensing capability. It is believed that incorporating the sensing attribute into cementitious composites will enhance benefits for sustainable civil infrastructures.
•Sulfamethoxazole (SMX) showed potent synergy with fluconazole against Candida auris.•Combination with newer azole drugs enhanced and broadened the spectrum of activity.•SMX–voriconazole displayed ...potent in vivo activity in a Caenorhabditis elegans infection model.•The mechanism of synergy was mediated by interference with the fungal folate pathway.•Mechanisms of azole resistance significantly impacted the synergistic relationship.
Candida auris is an emerging multidrug-resistant pathogen implicated in numerous outbreaks worldwide, with a notably high mortality rate (ca. 60%). A significant challenge with treatment of these infections is the resistance of C. auris to most antifungal drugs used clinically. Thus, finding co-drugs capable of overcoming resistance to frontline antifungals is of prime clinical importance. In this study, the ability of the combination of different sulfa drugs with azole antifungals to inhibit the growth of azole-resistant C. auris isolates was evaluated. Among the active sulfa drugs, sulfamethoxazole exhibited the most potent in vitro synergistic interactions with voriconazole and itraconazole. The sulfamethoxazole–voriconazole combination restored voriconazole's fungistatic activity against three of eight voriconazole-resistant clinical isolates. Similarly, the sulfamethoxazole–itraconazole combination restored itraconazole's fungistatic activity against three of four itraconazole-resistant clinical isolates. This activity was further confirmed in vivo in a Caenorhabditis elegans model of C. auris infection. The sulfamethoxazole–voriconazole combination enhanced survival of nematodes infected with C. auris by nearly 70%. Notably, these data indicate that the efficacy of this novel combination is dependent on the underlying mechanism of azole resistance. Mutant strains demonstrating azole resistance by either overproduction of or decreased affinity for the azole target (ERG11p) were found highly to be susceptible to the sulfamethoxazole–azole combination. However, this synergistic interaction was ineffective against mutant strains that demonstrated azole resistance via efflux pump hyperactivity. In conclusion, sulfamethoxazole represents a promising co-drug that can restore the efficacy of certain azole antifungal drugs against some azole-resistant isolates of C. auris.
Enterococci represent one of the microbial world's most challenging enigmas. Colonization of the gastrointestinal tract (GIT) of high-risk/immunocompromised patients by enterococci exhibiting ...resistance to vancomycin (VRE) can lead to life-threating infections, including bloodstream infections and endocarditis. Decolonization of VRE from the GIT of high-risk patients represents an alternative method to suppress the risk of the infection. It could be considered as a preventative measure to protect against VRE infections in high-risk individuals. Though multiple agents (ramoplanin and bacitracin) have been evaluated clinically, no drugs are currently approved for use in VRE decolonization of the GIT. The present study evaluates ebselen, a clinical molecule, for use as a decolonizing agent against VRE. When evaluated against a broad array of enterococcal isolates in vitro, ebselen was found to be as potent as linezolid (minimum inhibitory concentration against 90% of clinical isolates tested was 2 μg/ml). Though VRE has a remarkable ability to develop resistance to antibacterial agents, no resistance to ebselen emerged after a clinical isolate of vancomycin-resistant E. faecium was serially-passaged with ebselen for 14 days. Against VRE biofilm, a virulence factor that enables the bacteria to colonize the gut, ebselen demonstrated the ability to both inhibit biofilm formation and disrupt mature biofilm. Furthermore, in a murine VRE colonization reduction model, ebselen proved as effective as ramoplanin in reducing the bacterial shedding and burden of VRE present in the fecal content (by > 99.99%), cecum, and ileum of mice. Based on the promising results obtained, ebselen warrants further investigation as a novel decolonizing agent to quell VRE infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Candida species are a leading source of healthcare infections globally. The limited number of antifungal drugs combined with the isolation of Candida species, namely C. albicans and C. auris, ...exhibiting resistance to current antifungals necessitates the development of new therapeutics. The present study tested 85 synthetic phenylthiazole small molecules for antifungal activity against drug-resistant C. albicans. Compound 1 emerged as the most potent molecule, inhibiting growth of C. albicans and C. auris strains at concentrations ranging from 0.25-2 µg/mL. Additionally, compound 1 inhibited growth of other clinically-relevant yeast (Cryptococcus) and molds (Aspergillus) at a concentration as low as 0.50 µg/mL. Compound 1 exhibited rapid fungicidal activity, reducing the burden of C. albicans and C. auris below the limit of detection within 30 minutes. Compound 1 exhibited potent antibiofilm activity, similar to amphotericin B, reducing the metabolic activity of adherent C. albicans and C. auris biofilms by more than 66% and 50%, respectively. Furthermore, compound 1 prolonged survival of Caenorhabditis elegans infected with strains of C. albicans and C. auris, relative to the untreated control. The present study highlights phenylthiazole small molecules, such as compound 1, warrant further investigation as novel antifungal agents for drug-resistant Candida infections.
Antimicrobial peptides (AMPs) represent a promising therapeutic alternative for the treatment of antibiotic-resistant bacterial infections. The present study investigates the antimicrobial activity ...of new, rationally-designed derivatives of a short α-helical peptide, RR. From the peptides designed, RR4 and its D-enantiomer, D-RR4, emerged as the most potent analogues with a more than 32-fold improvement in antimicrobial activity observed against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Remarkably, D-RR4 demonstrated potent activity against colistin-resistant strains of P. aeruginosa (isolated from cystic fibrosis patients) indicating a potential therapeutic advantage of this peptide over several AMPs. In contrast to many natural AMPs, D-RR4 retained its activity under challenging physiological conditions (high salts, serum, and acidic pH). Furthermore, D-RR4 was more capable of disrupting P. aeruginosa and A. baumannii biofilms when compared to conventional antibiotics. Of note, D-RR4 was able to bind to lipopolysaccharide to reduce the endotoxin-induced proinflammatory cytokine response in macrophages. Finally, D-RR4 protected Caenorhabditis elegans from lethal infections of P. aeruginosa and A. baumannii and enhanced the activity of colistin in vivo against colistin-resistant P. aeruginosa.
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