The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Abdul N. Hamood - One of the best experts on this subject based on the ideXlab platform.
-
New markers for sepsis caused by Pseudomonas aeruginosa during Burn Infection
Metabolomics, 2020Co-Authors: Moamen M. Elmassry, Nithya S. Mudaliar, Jane A. Colmer-hamood, Michael J. San Francisco, John A. Griswold, Sharmila Dissanaike, Abdul N. HamoodAbstract:Introduction Sepsis is a leading cause of mortality in Burn patients. One of the major causes of sepsis in Burn patients is Pseudomonas aeruginosa. We hypothesized that during dissemination from infected Burn wounds and subsequent sepsis, P. aeruginosa affects the metabolome of the blood resulting in changes to specific metabolites that would serve as biomarkers for early diagnosis of sepsis caused by P. aeruginosa . Objectives To identify specific biomarkers in the blood after sepsis caused by P. aeruginosa Infection of Burns. Methods Gas chromatography with time-of-flight mass spectrometry was used to compare the serum metabolome of mice that were thermally injured and infected with P. aeruginosa (B–I) to that of mice that were neither injured nor infected, mice that were injured but not infected, and mice that were infected but not injured. Results Serum levels of 19 metabolites were significantly increased in the B–I group compared to controls while levels of eight metabolites were significantly decreased. Thymidine, thymine, uridine, and uracil (related to pyrimidine metabolism ) , malate and succinate (a possible sign of imbalance in the tricarboxylic acid cycle), 5-oxoproline (related to glutamine and glutathione metabolism), and trans -4-hydroxyproline (a major component of the protein collagen) were increased. Products of amino acid metabolism were significantly decreased in the B–I group, including methionine, tyrosine, indole-3-acetate, and indole-3-propionate. Conclusion In all, 26 metabolites were identified, including a unique combination of five metabolites ( trans- 4-hydroxyproline, 5-oxoproline, glycerol-3-galactoside, indole-3-acetate, and indole-3-propionate) that could serve as a set of biomarkers for early diagnosis of sepsis caused by P. aeruginosa in Burn patients.
-
contribution of quorum sensing to the virulence of pseudomonas aeruginosa in Burn wound Infections
Infection and Immunity, 1999Co-Authors: Kendra P Rumbaugh, John A. Griswold, Barbara H Iglewski, Abdul N. HamoodAbstract:The Pseudomonas aeruginosa quorum-sensing systems, las and rhl, control the production of numerous virulence factors. In this study, we have used the Burned-mouse model to examine the contribution of quorum-sensing systems to the pathogenesis of P. aeruginosa Infections in Burn wounds. Different quorum-sensing mutants of P. aeruginosa PAO1 that were defective in the lasR, lasI, or rhlI gene or both the lasI and rhlI genes were utilized. The following parameters of the P. aeruginosa Infection were examined: (i) lethality to the Burned mouse, (ii) dissemination of the P. aeruginosa strain within the body of the infected mouse (by determining the numbers of CFU of P. aeruginosa within the liver and spleen), and (iii) spread of the P. aeruginosa strain within the Burned skin (by determining the numbers of CFU of P. aeruginosa at the inoculation site and at a site about 15 mm from the inoculation site [distant site]). In comparison with that of PAO1, the in vivo virulence of lasI, lasR, and rhlI mutants was significantly reduced. However, the most significant reduction in in vivo virulence was seen with the lasI rhlI mutant. The numbers of CFU that were recovered from the livers, spleens, and skin of mice infected with different mutants were significantly lower than those of PAO1. At 8 and 16 h post Burn Infection, comparable numbers of CFU of PAO1 and lasI and rhlI mutants were obtained from both the inoculation and distant sites of the Burned skin of infected mice. In contrast, CFU of the lasR mutant and the lasI rhlI double mutant were recovered only from the inoculation site of infected mice at 8 and 16 h post Burn Infection. The ability of a plasmid carrying either the lasI or rhlI gene or the lasI and rhlI genes to complement the defect of the lasI rhlI double mutant was also examined. The presence of any of these plasmids within the lasI rhlI double mutant significantly enhanced its in vivo virulence, as well as its ability to spread within the Burned skin. These results suggest that the quorum-sensing systems play an important role in the horizontal spread of P. aeruginosa within Burned skin and in the dissemination of P. aeruginosa within the bodies of Burned-and-infected mice and contributed to the overall virulence of P. aeruginosa in this animal model.
Kim D Janda - One of the best experts on this subject based on the ideXlab platform.
-
3 hydroxy 1 alkyl 2 methylpyridine 4 1h thiones inhibition of the pseudomonas aeruginosa virulence factor lasb
ACS Medicinal Chemistry Letters, 2012Co-Authors: Amanda L Garner, Anjali K Struss, Jessica L Fullagar, Arpita Agrawal, Amira Y Moreno, Seth M Cohen, Kim D JandaAbstract:Bacterial resistance coupled to our current arsenal of antibiotics presents us with a growing threat to public health, thus warranting the exploration of alternative antibacterial strategies. In particular, the targeting of virulence factors has been regarded as a “second generation” antibiotic approach. In Pseudomonas aeruginosa, a Zn2+ metalloprotease virulence factor, LasB or P. aeruginosa elastase, has been implicated in the development of P. aeruginosa-related keratitis, pneumonia, and Burn Infection. Moreover, the enzyme also plays a critical role in swarming and biofilm formation, both of which are processes that have been linked to antibiotic resistance. To further validate the importance of LasB in P. aeruginosa Infection, we describe our efforts toward the discovery of nonpeptidic small molecule inhibitors of LasB. Using identified compounds, we have confirmed the role that LasB plays in P. aeruginosa swarming and demonstrate the potential for LasB-targeted small molecules in studying antimicrob...
Michael R. Hamblin - One of the best experts on this subject based on the ideXlab platform.
-
antimicrobial blue light therapy for candida albicans Burn Infection in mice
Proceedings of SPIE, 2015Co-Authors: Michael R. Hamblin, Clinton K. Murray, Yunsong Zhang, Yucheng Wang, Tianhong DaiAbstract:In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans Infection in acutely Burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal Burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse Burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal Infection in mouse Burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse Burns infected with C. albicans in comparison to infected mouse Burns without blue light therapy (P=0.015).
-
Blue Light Rescues Mice from Potentially Fatal Pseudomonas aeruginosa Burn Infection: Efficacy, Safety, and Mechanism of Action
Antimicrobial agents and chemotherapy, 2012Co-Authors: Tianhong Dai, Asheesh Gupta, Ying-ying Huang, Rui Yin, Clinton K. Murray, Mark S. Vrahas, Margaret E. Sherwood, George P. Tegos, Michael R. HamblinAbstract:Blue light has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. However, the use of blue light for wound Infections has not been established yet. In this study, we demonstrated the efficacy of blue light at 415 nm for the treatment of acute, potentially lethal Pseudomonas aeruginosa Burn Infections in mice. Our in vitro studies demonstrated that the inactivation rate of P. aeruginosa cells by blue light was approximately 35-fold higher than that of keratinocytes (P = 0.0014). Transmission electron microscopy revealed blue light-mediated intracellular damage to P. aeruginosa cells. Fluorescence spectroscopy suggested that coproporphyrin III and/or uroporphyrin III are possibly the intracellular photosensitive chromophores associated with the blue light inactivation of P. aeruginosa. In vivo studies using an in vivo bioluminescence imaging technique and an area-under-the-bioluminescence-time-curve (AUBC) analysis showed that a single exposure of blue light at 55.8 J/cm2, applied 30 min after bacterial inoculation to the infected mouse Burns, reduced the AUBC by approximately 100-fold in comparison with untreated and infected mouse Burns (P < 0.0001). Histological analyses and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays indicated no significant damage in the mouse skin exposed to blue light at the effective antimicrobial dose. Survival analyses revealed that blue light increased the survival rate of the infected mice from 18.2% to 100% (P < 0.0001). In conclusion, blue light therapy might offer an effective and safe alternative to conventional antimicrobial therapy for P. aeruginosa Burn Infections.
-
Ultraviolet-C light for treatment of Candida albicans Burn Infection in mice.
Photochemistry and Photobiology, 2011Co-Authors: Tianhong Dai, Liyi Huang, Gitika B Kharkwal, Jie Zhao, Tyler G. St. Denis, Yumin Xia, Sulbha K Sharma, Christophe D'enfert, Michael R. HamblinAbstract:Burn patients are at high risk of invasive fungal Infections, which are a leading cause of morbidity, mortality, and related expense exacerbated by the emergence of drug resistant fungal strains. In this study, we investigated the use of UVC light (254 nm) for the treatment of yeast Candida albicans Infection in mouse third degree Burns. In vitro studies demonstrated that UVC could selectively kill the pathogenic C. albicans compared with a normal mouse keratinocyte cell line in a light exposure dependent manner. A mouse model of chronic C. albicans Infection in non-lethal third degree Burns was developed. The C. albicans strain was stably transformed with a version of the Gaussia princeps luciferase gene that allowed real-time bioluminescence imaging of the progression of C. albicans Infection. UVC treatment with a single exposure carried out on day 0 (30 min postInfection) gave an average 2.16-log(10)-unit (99.2%) loss of fungal luminescence when 2.92 J cm(-2) UVC had been delivered, while UVC 24 h postInfection gave 1.94-log(10)-unit (95.8%) reduction of fungal luminescence after 6.48 J cm(-2). Statistical analysis demonstrated that UVC treatment carried out on both day 0 and day 1 significantly reduced the fungal bioburden of infected Burns. UVC was found to be superior to a topical antifungal drug, nystatin cream. UVC was tested on normal mouse skin and no gross damage was observed 24 h after 6.48 J cm(-2). DNA lesions (cyclobutane pyrimidine dimers) were observed by immunofluorescence in normal mouse skin immediately after a 6.48 J cm(-2) UVC exposure, but the lesions were extensively repaired at 24 h after UVC exposure.
-
antimicrobial photodynamic therapy in a mouse model of acinetobacter baumannii Burn Infection
12th World Congress of the International Photodynamic Association, 2009Co-Authors: Tianhong Dai, George P. Tegos, Michael R. Hamblin, Timur Zhiyentayev, Liyi Huang, Michael J Franklin, David G BaerAbstract:Multi-drug resistant Acinetobacter baumanii Infections represent a growing problem, especially in traumatic wounds and Burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment using traditional antibiotics can be extremely difficult and new antimicrobial approaches are being investigated. One of these antimicrobial alternatives could be the combination of non-toxic photosensitizers (PS) and visible light known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full thickness thermal Burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by covalent conjugation chlorin(e6) to polyethylenimine followed by illumination of the Burn surface with red light. Application of 10 8 A. baumannii cells to the surface of 10-second Burns made on the dorsal surface of shaved female BALB/c mice led to chronic Infections that lasted on average 22 days characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after applying bacteria gave over three logs of loss of bacterial luminescence in a light exposure dependent manner, while PDT carried out on day 1 and day 2 gave approximately a 1.7-log reduction. Application of PS dissolved in 10% or 20% DMSO without light gave only modest reduction in bacterial luminescence from mouse Burns. Some bacterial regrowth in the treated Burn was observed but was generally modest. It was also found that PDT did not lead to inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multi-drug resistant localized A. baumannii Infections.
Amanda L Garner - One of the best experts on this subject based on the ideXlab platform.
-
3 hydroxy 1 alkyl 2 methylpyridine 4 1h thiones inhibition of the pseudomonas aeruginosa virulence factor lasb
ACS Medicinal Chemistry Letters, 2012Co-Authors: Amanda L Garner, Anjali K Struss, Jessica L Fullagar, Arpita Agrawal, Amira Y Moreno, Seth M Cohen, Kim D JandaAbstract:Bacterial resistance coupled to our current arsenal of antibiotics presents us with a growing threat to public health, thus warranting the exploration of alternative antibacterial strategies. In particular, the targeting of virulence factors has been regarded as a “second generation” antibiotic approach. In Pseudomonas aeruginosa, a Zn2+ metalloprotease virulence factor, LasB or P. aeruginosa elastase, has been implicated in the development of P. aeruginosa-related keratitis, pneumonia, and Burn Infection. Moreover, the enzyme also plays a critical role in swarming and biofilm formation, both of which are processes that have been linked to antibiotic resistance. To further validate the importance of LasB in P. aeruginosa Infection, we describe our efforts toward the discovery of nonpeptidic small molecule inhibitors of LasB. Using identified compounds, we have confirmed the role that LasB plays in P. aeruginosa swarming and demonstrate the potential for LasB-targeted small molecules in studying antimicrob...
Pan Wang - One of the best experts on this subject based on the ideXlab platform.
-
Smart Hydrogel-Based DVDMS/bFGF Nanohybrids for Antibacterial Phototherapy with Multiple Damaging Sites and Accelerated Wound Healing.
ACS applied materials & interfaces, 2020Co-Authors: Bingjie Mai, Yiru Gao, Xiaobing Wang, Quanhong Liu, Mengqi Jia, Shupei Liu, Zonghai Sheng, Pan WangAbstract:Burn Infection is one of the commonest causes of death in severely Burned patients. Developing multifunctional biological nanomaterials has a great significance for the comprehensive treatment of Burn Infection. In this paper, we developed a hydrogel-based nanodelivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of Burns. The treatment system is mainly composed of porphyrin photosensitizer sinoporphyrin sodium (DVDMS) and poly(lactic-co-glycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres that are embedded in carboxymethyl chitosan (CMCS)–sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging, and biocompatibility of the CSDP nanosystem. Under mild photoirradiation (30 J/cm2, 5 min), 10 μg/mL CSDP showed excellent antibacterial and anti-biofilm activities, which eradi...
-
Photodynamic antimicrobial chemotherapy for Staphylococcus aureus and multidrug-resistant bacterial Burn Infection in vitro and in vivo
International journal of nanomedicine, 2017Co-Authors: Bingjie Mai, Yiru Gao, Xiaobing Wang, Kun Zhang, Quanhong Liu, Pan WangAbstract:Background and objectives Antibiotic resistance has emerged as one of the most important determinants of outcome in patients with serious Infections, along with the virulence of the underlying pathogen. Photodynamic antimicrobial chemotherapy (PACT) has been proposed as an alternative approach for the inactivation of bacteria. This study aims to evaluate the antibacterial effect of sinoporphyrin sodium (DVDMS)-mediated PACT on Staphylococcus aureus and multidrug resistant S. aureus in vitro and in vivo. Materials and methods Bacteria were incubated with DVDMS and exposed to treatment with light. After PACT treatment, colony-forming units were counted to estimate the bactericidal effect. Intracellular reactive oxygen-species production was detected by flow cytometry. Flow cytometry and fluorescence-microscopy detection of bacterial cell-membrane permeability. Enzyme-linked immunosorbent assays were used to determine expression of VEGF, TGFβ1, TNFα, IL6, and bFGF factors in Burn Infection. Results DVDMS-PACT effectively killed bacterial proliferation. Intracellular ROS levels were enhanced obviously in the PACT-treatment group. SYTO 9 and propidium iodide staining showed a decrease in the ratio of green:red fluorescence intensity in the PACT-treatment group in comparison to the control group. Enzyme-linked immunosorbent-assay results revealed that in the healing process, the expression of bFGF, TGFβ1, and VEGF in the treatment group were higher than in the control group, which inhibited inflammation-factor secretion. In addition, skin-tissue bacteria were reduced after treatment. Conclusion These results indicate that DVDMS-PACT presents significant bactericidal activity and promotes wound healing after Burn Infections.
