scholarly journals Synergistic Combination of Chitosan Acetate with Nanoparticle Silver as a Topical Antimicrobial: Efficacy against Bacterial Burn Infections

2011 ◽  
Vol 55 (7) ◽  
pp. 3432-3438 ◽  
Author(s):  
Liyi Huang ◽  
Tianhong Dai ◽  
Yi Xuan ◽  
George P. Tegos ◽  
Michael R. Hamblin

ABSTRACTChitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit thein vitrogrowth of Gram-positive methicillin-resistantStaphylococcus aureus(MRSA) and Gram-negative bacteria (Pseudomonas aeruginosa,Proteus mirabilis, andAcinetobacter baumannii), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in anin vivoburn model infected with bioluminescentP. aeruginosa. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (P= 0.0082 versus regular chitosan andP= 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections.

2015 ◽  
Vol 59 (5) ◽  
pp. 2720-2725 ◽  
Author(s):  
Dana R. Bowers ◽  
Henry Cao ◽  
Jian Zhou ◽  
Kimberly R. Ledesma ◽  
Dongxu Sun ◽  
...  

ABSTRACTAntimicrobial resistance amongAcinetobacter baumanniiis increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates ofA. baumannii. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 μg/ml). Time-kill studies were performed over 24 h using approximately 106CFU/ml of each strain with clinically relevant minocycline concentrations (2 μg/ml and 8 μg/ml), with and without polymyxin B (0.5 μg/ml). Thein vivoefficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥4×) was observed in the presence of PAβN. The intracellular concentration andin vitrobactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated.


2016 ◽  
Vol 60 (8) ◽  
pp. 5023-5025 ◽  
Author(s):  
Sabrina R. Itaqui ◽  
Camila M. Verdi ◽  
Juliana S. M. Tondolo ◽  
Thaisa S. da Luz ◽  
Sydney H. Alves ◽  
...  

ABSTRACTWe describe herein vitroactivity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC90between 2 and 32 μg∕ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%).In vivoexperimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused byPythium insidiosum.


2015 ◽  
Vol 60 (2) ◽  
pp. 881-889 ◽  
Author(s):  
Eric F. Kong ◽  
Christina Tsui ◽  
Heather Boyce ◽  
Ahmed Ibrahim ◽  
Stephen W. Hoag ◽  
...  

ABSTRACTOral candidiasis (OC), caused by the fungal pathogenCandida albicans, is the most common opportunistic infection in HIV+individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluatedin vitrofor gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was testedin vivoin our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viableC. albicanscounts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection withC. albicanswere effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent.


mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Marcin Krupka ◽  
Marta Sobrinos-Sanguino ◽  
Mercedes Jiménez ◽  
Germán Rivas ◽  
William Margolin

ABSTRACTZipA is an essential cell division protein inEscherichia coli. Together with FtsA, ZipA tethers dynamic polymers of FtsZ to the cytoplasmic membrane, and these polymers are required to guide synthesis of the cell division septum. This dynamic behavior of FtsZ has been reconstituted on planar lipid surfacesin vitro, visible as GTP-dependent chiral vortices several hundred nanometers in diameter, when anchored by FtsA or when fused to an artificial membrane binding domain. However, these dynamics largely vanish when ZipA is used to tether FtsZ polymers to lipids at high surface densities. This, along with somein vitrostudies in solution, has led to the prevailing notion that ZipA reduces FtsZ dynamics by enhancing bundling of FtsZ filaments. Here, we show that this is not the case. When lower, more physiological levels of the soluble, cytoplasmic domain of ZipA (sZipA) were attached to lipids, FtsZ assembled into highly dynamic vortices similar to those assembled with FtsA or other membrane anchors. Notably, at either high or low surface densities, ZipA did not stimulate lateral interactions between FtsZ protofilaments. We also usedE. colimutants that are either deficient or proficient in FtsZ bundling to provide evidence that ZipA does not directly promote bundling of FtsZ filamentsin vivo. Together, our results suggest that ZipA does not dampen FtsZ dynamics as previously thought, and instead may act as a passive membrane attachment for FtsZ filaments as they treadmill.IMPORTANCEBacterial cells use a membrane-attached ring of proteins to mark and guide formation of a division septum at midcell that forms a wall separating the two daughter cells and allows cells to divide. The key protein in this ring is FtsZ, a homolog of tubulin that forms dynamic polymers. Here, we use electron microscopy and confocal fluorescence imaging to show that one of the proteins required to attach FtsZ polymers to the membrane duringE. colicell division, ZipA, can promote dynamic swirls of FtsZ on a lipid surfacein vitro. Importantly, these swirls are observed only when ZipA is present at low, physiologically relevant surface densities. Although ZipA has been thought to enhance bundling of FtsZ polymers, we find little evidence for bundlingin vitro. In addition, we present several lines ofin vivoevidence indicating that ZipA does not act to directly bundle FtsZ polymers.


2015 ◽  
Vol 45 (2) ◽  
pp. 190-212 ◽  
Author(s):  
Z. F. Bhat ◽  
Sunil Kumar ◽  
Hina Fayaz Bhat

Purpose – The aim of the article was to focus on various peptides identified in the egg and their probable application as novel ingredients in the development of functional food products. Bioactive peptides of egg origin have attracted increasing interest as one of the prominent candidates for development of various health-promoting functional and designer foods. Design/methodology/approach – Traditionally known as a source of highly valuable proteins in human nutrition, eggs are nowadays also considered as an important source of many bioactive peptides which may find wide application in medicine and food production. These specific protein fragments from egg proteins which, above and beyond their nutritional capabilities, have a positive impact on the body’s function or condition by affecting the digestive, endocrine, cardiovascular, immune and nervous systems, and may ultimately influence health. Findings – Several peptides that are released in vitro or in vivo from egg proteins have been attributed to different health effects, including antihypertensive effects, antimicrobial properties, antioxidant activities, anticancer activity, immunomodulating activity, antiadhesive properties and enhancement of nutrient absorption and/or bioavailability. Extensive research has been undertaken to identify and characterize these biologically active peptides of egg origin which has changed the image of egg as a new source of biologically active ingredients for the development of functional foods with specific benefits for human health and treatment and prevention of diseases. Originality/value – The paper mainly describes the above-stated properties of bioactive peptides derived from egg proteins.


2016 ◽  
Vol 60 (7) ◽  
pp. 4283-4289 ◽  
Author(s):  
Bo Ma ◽  
Chao Niu ◽  
Ying Zhou ◽  
Xiaoyan Xue ◽  
Jingru Meng ◽  
...  

ABSTRACTThanatin (THA) displays potent antibiotic activity, especially against extended-spectrum-β-lactamase (ESBL)-producingEscherichia colibothin vitroandin vivo, with minimal hemolytic toxicity and satisfactory stability in plasma. However, the high cost of thanatin significantly limits its development and clinical application. To reduce the cost of peptide synthesis, a formulation of cyclic thanatin (C-thanatin) called linear thanatin (L-thanatin) was synthesized and its activity was evaluatedin vivoandin vitro. Results showed that C-thanatin and L-thanatin MICs did not differ against eight Gram-negative and two Gram-positive bacterial strains. Furthermore, the survival rates of ESBL-producing-E. coli-infected mice were consistent after C-thanatin or L-thanatin treatment at 5 or 10 mg/kg of body weight. Neither C-thanatin nor L-thanatin showed toxicity for human red blood cells (hRBCs) and human umbilical vein endothelial cells (HUVECs) at a concentration as high as 256 μg/ml. Results of circular dichroism spectroscopy indicated that the secondary structure of L-thanatin is extremely similar to that of C-thanatin. Membrane permeabilization and depolarization assays showed that C-thanatin and L-thanatin have similar abilities to permeabilize the outer and inner membranes and to induce membrane depolarization in ESBL-producingE. coli. However, neither of them caused significant HUVEC membrane permeability. These findings indicate that the two peptides have similar effects on bacterial cell membranes and that the disulfide bond in thanatin is not essential for its antimicrobial activitiesin vivoandin vitro. L-thanatin is thus a promising low-cost peptide candidate for treating ESBL-producingE. coliinfections.


2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Laís Salomão Arias ◽  
Mark C. Butcher ◽  
Bryn Short ◽  
Emily McKloud ◽  
Chris Delaney ◽  
...  

ABSTRACT Candida auris has emerged as a multidrug-resistant nosocomial pathogen over the last decade. Outbreaks of the organism in health care facilities have resulted in life-threatening invasive candidiasis in over 40 countries worldwide. Resistance by C. auris to conventional antifungal drugs such as fluconazole and amphotericin B means that alternative therapeutics must be explored. As such, this study served to investigate the efficacy of a naturally derived polysaccharide called chitosan against aggregative (Agg) and nonaggregative (non-Agg) isolates of C. auris in vitro and in vivo. In vitro results indicated that chitosan was effective against planktonic and sessile forms of Agg and non-Agg C. auris. In a Galleria mellonella model to assess C. auris virulence, chitosan treatment was shown to ameliorate killing effects of both C. auris phenotypes (NCPF 8973 and NCPF 8978, respectively) in vivo. Specifically, chitosan reduced the fungal load and increased survival rates of infected Galleria, while treatment alone was nontoxic to the larvae. Finally, chitosan treatment appeared to induce a stress-like gene expression response in NCPF 8973 in the larvae likely arising from a protective response by the organism to resist antifungal activity of the compound. Taken together, results from this study demonstrate that naturally derived compounds such as chitosan may be useful alternatives to conventional antifungals against C. auris.


2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Sonya A. Trinh ◽  
Hannah E. Gavin ◽  
Karla J. F. Satchell

ABSTRACT Foodborne Vibrio vulnificus infections are associated with higher rates of sepsis and mortality than wound infections; however, antibiotic efficacy studies have not been performed in foodborne infection models. The efficacies of ceftriaxone, cefepime, doxycycline, ciprofloxacin, and combination therapy were assessed in V. vulnificus intestinal infection in mice in order to model foodborne infections. In accordance with prior studies of cefotaxime, cefepime was synergistic with doxycycline and ciprofloxacin in vitro; combination therapy significantly decreased bacterial growth, by ≥2 log10 units, from that with antibiotic monotherapy (P < 0.01). In vivo, survival rates in the ceftriaxone (50%), doxycycline (79%), and ciprofloxacin (80%) groups were significantly higher than those in the control group (0%) (P < 0.0001). Survival was significantly higher with ceftriaxone-doxycycline (91%) or ceftriaxone-ciprofloxacin (100%) therapy than with ceftriaxone (50%) (P ≤ 0.05). Survival with cefepime-doxycycline (96%) or cefepime-ciprofloxacin (90%) therapy was significantly higher than that with cefepime alone (20%) (P < 0.001). There was no difference in survival between the combination therapy groups. Thus, we conclude that combination therapy was the most effective treatment for foodborne V. vulnificus septicemia. In a septic patient with a recent ingestion of raw seafood, cefepime in combination with doxycycline or ciprofloxacin should be initiated for coverage of resistant Gram-negative organisms and V. vulnificus pending a microbiological diagnosis. Once a diagnosis of foodborne V. vulnificus septicemia is established, treatment can safely transition to ceftriaxone in combination with doxycycline or ciprofloxacin.


2018 ◽  
Vol 47 (6) ◽  
pp. 490-495 ◽  
Author(s):  
Noraini Mahmad ◽  
R.M. Taha ◽  
Rashidi Othman ◽  
Sakinah Abdullah ◽  
Nordiyanah Anuar ◽  
...  

PurposeThe purpose of this paper is to validate the antimicrobial activity (both antibacterial and antifungal) ofin vivoandin vitroethanolic anthocyanin extracts ofClitoria ternateaL. (vivid blue flower butterfly-pea) andDioscorea alataL. (purple yam) against selected bacteria (Bacillus subtilis,Staphylococcus aureusandEscherichia coli) and fungi (Fusarium sp.,Aspergillus nigerandTrichoderma sp.).Design/methodology/approachThe freeze-dried samples (0.2 g) fromin vivovivid blue flowers ofC. ternateaL. were extracted using 10 mL ethanol (produced ethanolic red extraction) and 10 mL distilled water (produced aqueous blue extraction) separately. Two-month-oldin vitrocallus samples (0.2 g) were only extracted using 10 mL ethanol. The anthocyanin extractions were separated with the addition (several times) of ethyl acetate and distilled water (1:2:3) to remove stilbenoids, chlorophyll, less polar flavonoids and other non-polar compounds. Furthermore, the antimicrobial properties were determined using agar diffusion technique. Three bacteria (B. subtilis,S. aureusandE. coli) and fungi (F. sp.,A. nigerandT. sp.) were streaked on bacteria agar and dextrose agar, respectively, using “hockey stick”. Then, the sterile paper discs (6 mm diameter) were pipetted with 20 µL of 1,010 CFU/mL chloramphenicol (as control for antibacterial) and carbendazim (as control for antifungal)in vivoandin vitroextracts. The plates were incubated at room temperature for 48 h, and the inhibition zones were measured.FindingsBased on the results, bothin vivoandin vitroethanolic extracts from vivid blue flowers ofC. ternateaL. showed the best antibacterial activity against the same bacteria (B. subtilis), 11 and 10 mm inhibition zones, respectively. However, different antifungal activity was detected inin vitroethanolic callus extract (12 mm), which was againstT. sp., contrary toin vivoethanolic extract (10 mm), which was againstF. sp.; antibacterial activity ofD. alataL. was seen against the same bacteria (E. coli) with the highest inhibition zone forin vivoextract (8.8 mm), followed byin vitroextract (7.8 mm).Research limitations/implicationsAnthocyanins are responsible for the water soluble and vacuolar, pink, red, purple and blue pigments present in coloured plant pigments. These pigments (pink, red, purple and blue) are of important agronomic value in many crops and ornamental plants. However, anthocyanins are not stable and are easy to degrade and fade whenever exposed to light.Social implicationsPlant extracts containing bioactive agents with antimicrobial properties have been found to be useful in treating bacterial and fungal infections, as well as showed multiple antibiotic resistance.Originality/valueBothin vivoandin vitroextracts from vivid blue flower petals (C. ternateaL.) and purple yam (D. alataL.) have important applications as natural antimicrobial (antibacterial and antifungal) agents in the coating industry, instead of natural pharmaceutical products.


2016 ◽  
Vol 60 (8) ◽  
pp. 4983-4990 ◽  
Author(s):  
Rym Boudjemaa ◽  
Romain Briandet ◽  
Matthieu Revest ◽  
Cédric Jacqueline ◽  
Jocelyne Caillon ◽  
...  

ABSTRACTStaphylococcus aureusis one of the most frequent pathogens responsible for biofilm-associated infections (BAI), and the choice of antibiotics to treat these infections remains a challenge for the medical community. In particular, daptomycin has been reported to fail against implant-associatedS. aureusinfections in clinical practice, while its association with rifampin remains a good candidate for BAI treatment. To improve our understanding of such resistance/tolerance toward daptomycin, we took advantage of the dynamic fluorescence imaging tools (time-lapse imaging and fluorescence recovery after photobleaching [FRAP]) to locally and accurately assess the antibiotic diffusion reaction in methicillin-susceptible and methicillin-resistantS. aureusbiofilms. To provide a realistic representation of daptomycin action, we optimized anin vitromodel built on the basis of our recently publishedin vivomouse model of prosthetic vascular graft infections. We demonstrated that at therapeutic concentrations, daptomycin was inefficient in eradicating biofilms, while the matrix was not a shield to antibiotic diffusion and to its interaction with its bacterial target. In the presence of rifampin, daptomycin was still present in the vicinity of the bacterial cells, allowing prevention of the emergence of rifampin-resistant mutants. Conclusions derived from this study strongly suggest thatS. aureusbiofilm resistance/tolerance toward daptomycin may be more likely to be related to a physiological change involving structural modifications of the membrane, which is a strain-dependent process.


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