scholarly journals Use of the Antimicrobial Peptide Pardaxin (GE33) To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice with Skin Injuries

2013 ◽  
Vol 58 (3) ◽  
pp. 1538-1545 ◽  
Author(s):  
Han-Ning Huang ◽  
Chieh-Yu Pan ◽  
Yi-Lin Chan ◽  
Jyh-Yih Chen ◽  
Chang-Jer Wu
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Lethal Dose ◽  
Antimicrobial Activities ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antimicrobial Function ◽  
Monocytes And Macrophages ◽  
Endothelial Growth Factor

ABSTRACTAntimicrobial peptides (AMPs) have recently been determined to be potential candidates for treating drug-resistant bacterial infections. Pardaxin (GE33), a marine antimicrobial peptide, has been reported to possess antimicrobial function. In this study, we investigated whether pardaxin promoted healing of contaminated wounds in mice. One square centimeter of outer skin was excised from the ventral region of mice, and a lethal dose of methicillin-resistantStaphylococcus aureus(MRSA) was applied in the presence or absence of methicillin, vancomycin, or pardaxin. While untreated mice and mice treated with methicillin died within 3 days, mice treated with pardaxin survived infection. Pardaxin decreased MRSA bacterial counts in the wounded region and also enhanced wound closure. Reepithelialization and dermal maturation were also faster in mice treated with pardaxin than in mice treated with vancomycin. In addition, pardaxin treatment controlled excess recruitment of monocytes and macrophages and increased the expression of vascular endothelial growth factor (VEGF). In conclusion, these results suggest that pardaxin is capable of enhancing wound healing. Furthermore, this study provides an excellent platform for comparing the antimicrobial activities of peptide and nonpeptide antibiotics.

scholarly journals Targeting Methicillin-Resistant Staphylococcus aureus with Short Salt-Resistant Synthetic Peptides

2014 ◽  
Vol 58 (7) ◽  
pp. 4113-4122 ◽  
Author(s):  
Mohamed F. Mohamed ◽  
Maha I. Hamed ◽  
Alyssa Panitch ◽  
Mohamed N. Seleem
Keyword(s):  
Staphylococcus Aureus ◽  
Synthetic Peptides ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Net Charge ◽  
Methicillin Resistant ◽  
Content Type ◽  
C Terminus ◽  
Conventional Antibiotics

ABSTRACTThe seriousness of microbial resistance combined with the lack of new antimicrobials has increased interest in the development of antimicrobial peptides (AMPs) as novel therapeutics. In this study, we evaluated the antimicrobial activities of two short synthetic peptides, namely, RRIKA and RR. These peptides exhibited potent antimicrobial activity againstStaphylococcus aureus, and their antimicrobial effects were significantly enhanced by addition of three amino acids in the C terminus, which consequently increased the amphipathicity, hydrophobicity, and net charge. Moreover, RRIKA and RR demonstrated a significant and rapid bactericidal effect against clinical and drug-resistantStaphylococcusisolates, including methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-intermediateS. aureus(VISA), vancomycin-resistantS. aureus(VRSA), linezolid-resistantS. aureus, and methicillin-resistantStaphylococcus epidermidis. In contrast to many natural AMPs, RRIKA and RR retained their activity in the presence of physiological concentrations of NaCl and MgCl2. Both RRIKA and RR enhanced the killing of lysostaphin more than 1,000-fold and eradicated MRSA and VRSA isolates within 20 min. Furthermore, the peptides presented were superior in reducing adherent biofilms ofS. aureusandS. epidermidiscompared to results with conventional antibiotics. Our findings indicate that the staphylocidal effects of our peptides were through permeabilization of the bacterial membrane, leading to leakage of cytoplasmic contents and cell death. Furthermore, peptides were not toxic to HeLa cells at 4- to 8-fold their antimicrobial concentrations. The potent and salt-insensitive antimicrobial activities of these peptides present an attractive therapeutic candidate for treatment of multidrug-resistantS. aureusinfections.

scholarly journals Antimicrobial activities of Bacillus velezensis strains isolated from stingless bee products against methicillin-resistant Staphylococcus aureus

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251514
Author(s):  
Mohamad Malik Al-adil Baharudin ◽  
Mohamad Syazwan Ngalimat ◽  
Fairolniza Mohd Shariff ◽  
Zetty Norhana Balia Yusof ◽  
Murni Karim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
High Performance ◽  
Pathogenic Bacteria ◽  
Antimicrobial Activities ◽  
Proteinase K ◽  
Tween 20 ◽  
Bacillus Velezensis ◽  
Promising Alternative ◽  
Methicillin Resistant

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have reached epidemic proportions globally. Therefore, there is an urgent need for a continuous supply of antibiotics to combat the problem. In this study, bacteria initially identified as species belonging to the Bacillus amyloliquefaciens operational group were re-identified based on the housekeeping gene, gyrB. Cell-free supernatants (CFS) from the strains were used for antimicrobial tests using the agar well diffusion assay against MRSA and various types of pathogenic bacteria. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and physicochemical characteristics of the CFS were determined. Based on gyrB sequence analysis, five strains (PD9, B7, PU1, BP1 and L9) were identified as Bacillus velezensis. The CFS of all B. velezensis strains showed broad inhibitory activities against Gram-negative and -positive as well as MRSA strains. Strain PD9 against MRSA ATCC 33742 was chosen for further analysis as it showed the biggest zone of inhibition (21.0 ± 0.4 mm). The MIC and MBC values obtained were 125 μl/ml. The crude antimicrobial extract showed bactericidal activity and was stable at various temperatures (40–80°C), pH (4–12), surfactants (Tween 20, Tween 80, SDS and Triton X-100) and metal ions (MgCI2, NaCI2, ZnNO3 and CuSO4) when tested. However, the crude extract was not stable when treated with proteinase K. All these properties resembled the characteristics of peptides. The antimicrobial compound from the selected strain was purified by using solvent extraction method and silica gel column chromatography. The purified compound was subjected to High Performance Liquid Chromatography which resulted in a single peak of the anti-MRSA compound being detected. The molecular weight of the anti-MRSA compound was determined by using SDS-PAGE and zymogram. The size of the purified antimicrobial peptide was approximately ~ 5 kDa. The antimicrobial peptide produced from B. velezensis strain PD9 is a promising alternative to combat the spread of MRSA infections in the future.

scholarly journals Evaluation of Vancomycin in Combination with Piperacillin-Tazobactam or Oxacillin against Clinical Methicillin-Resistant Staphylococcus aureus Isolates and Vancomycin-Intermediate S. aureus IsolatesIn Vitro

2013 ◽  
Vol 58 (2) ◽  
pp. 1028-1033 ◽  
Author(s):  
Thomas J. Dilworth ◽  
Jora Sliwinski ◽  
Keenan Ryan ◽  
Monique Dodd ◽  
Renée-Claude Mercier
Keyword(s):  
Staphylococcus Aureus ◽  
Empirical Therapy ◽  
Antimicrobial Activities ◽  
Synergistic Activity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Zones Of Inhibition ◽  
The Mean ◽  
Time Kill

ABSTRACTVancomycin with piperacillin-tazobactam is used as empirical therapy for critically ill patients. Studies of this combination against methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-intermediateS. aureus(VISA) are limited, but β-lactams in combination with vancomycin have shown synergistic activity against MRSA and VISA. The goal of this study was to evaluate whether piperacillin-tazobactam and vancomycin were synergistic against MRSA and VISAin vitro. Bloodstream MRSA (n= 20) and VISA (n= 4) strains were selected.In vitroantimicrobial activities of piperacillin-tazobactam and oxacillin were evaluated by disk diffusion, and MICs were determined by Etest using Muller-Hinton agar with and without vancomycin at one-half the MIC. Time-kill studies evaluated 14 MRSA and all 4 VISA isolates using piperacillin-tazobactam at 300/35 mg/liter or oxacillin at 40 mg/liter alone and with vancomycin at one-half the MIC. Mean zones of inhibition for piperacillin-tazobactam and oxacillin increased with vancomycin against MRSA and VISA (P< 0.001 for all), and the MIC90decreased with vancomycin against MRSA and VISA to values meeting susceptibility criteria forS. aureus(P< 0.001 for both antibiotics against MRSA). In MRSA time-kill studies, the mean 24-h reductions in inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 3.53, 3.69, and 2.62 log10CFU/ml, respectively. The mean 24-h reductions in VISA inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 2.85, 2.93, and 3.45 log10CFU/ml, respectively. Vancomycin with piperacillin-tazobactam or oxacillin demonstrated synergistic activity against MRSA and VISA. The clinical implications of these combinations against MRSA and VISA should be investigated.

scholarly journals Combining the FtsZ-Targeting Prodrug TXA709 and the Cephalosporin Cefdinir Confers Synergy and Reduces the Frequency of Resistance in Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 60 (7) ◽  
pp. 4290-4296 ◽  
Author(s):  
Malvika Kaul ◽  
Lilly Mark ◽  
Ajit K. Parhi ◽  
Edmond J. LaVoie ◽  
Daniel S. Pilch
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Drug Dose ◽  
Drug Induced ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Emergence Of Resistance

ABSTRACTCombination therapy of bacterial infections with synergistic drug partners offers distinct advantages over monotherapy. Among these advantages are (i) a reduction of the drug dose required for efficacy, (ii) a reduced potential for drug-induced toxicity, and (iii) a reduced potential for the emergence of resistance. Here, we describe the synergistic actions of the third-generation oral cephalosporin cefdinir and TXA709, a new, FtsZ-targeting prodrug that we have developed with improved pharmacokinetics and enhancedin vivoefficacy against methicillin-resistantStaphylococcus aureus(MRSA) relative to earlier agents. We show that the active product of TXA709 (TXA707) acts synergistically with cefdinirin vitroagainst clinical isolates of MRSA, vancomycin-intermediateS. aureus(VISA), vancomycin-resistantS. aureus(VRSA), and linezolid-resistantS. aureus(LRSA). In addition, relative to TXA707 alone, the combination of TXA707 and cefdinir significantly reduces or eliminates the detectable emergence of resistance. We also demonstrate synergyin vivowith oral administration of the prodrug TXA709 and cefdinir in mouse models of both systemic and tissue (thigh) infections with MRSA. This synergy reduces the dose of TXA709 required for efficacy 3-fold. Viewed as a whole, our results highlight the potential of TXA709 and cefdinir as a promising combination for the treatment of drug-resistant staphylococcal infections.

scholarly journals Antimicrobial Activities of Ceftaroline and Comparator Agents against Bacterial Organisms Causing Bacteremia in Patients with Skin and Skin Structure Infections in U.S. Medical Centers, 2008 to 2014

2016 ◽  
Vol 60 (4) ◽  
pp. 2558-2563 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Rodrigo E. Mendes ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Activities ◽  
Methicillin Resistant ◽  
Content Type ◽  
Skin Structure ◽  
E Coli ◽  
Medical Centers

ABSTRACTWe evaluated the antimicrobial susceptibility of 1,454 organisms consecutively collected from patients with bacteremia associated with skin and skin structure infections. The most common organisms obtained wereStaphylococcus aureus(670 organisms [46.1%]),Escherichia coli(200 organisms [13.8%]), β-hemolytic streptococci (βHS) (138 organisms [9.5%]), andKlebsiella pneumoniae(109 organisms [7.5%]). The susceptibility rates for ceftaroline were 97.9% forS. aureus(95.9% among methicillin-resistantS. aureus[MRSA]), 100.0% for βHS, 86.5% forE. coli, and 89.0% forK. pneumoniae. Ceftaroline and tigecycline provided the best overall coverage.

scholarly journals In VitroActivities of LTX-109, a Synthetic Antimicrobial Peptide, against Methicillin-Resistant, Vancomycin-Intermediate, Vancomycin-Resistant, Daptomycin-Nonsusceptible, and Linezolid-Nonsusceptible Staphylococcus aureus

2012 ◽  
Vol 56 (8) ◽  
pp. 4478-4482 ◽  
Author(s):  
Louis D. Saravolatz ◽  
Joan Pawlak ◽  
Leonard Johnson ◽  
Hector Bonilla ◽  
Louis D. Saravolatz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Time Kill ◽  
Dose Dependent

ABSTRACTLTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistantStaphylococcus aureus(MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediateS. aureus(VISA), and vancomycin-resistantS. aureus(VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity againstS. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.

scholarly journals A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus aureus

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Nabil M. Abraham ◽  
Lei Liu ◽  
Brandon L. Jutras ◽  
Kristen Murfin ◽  
Ali Acar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Repeat Region ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antifreeze Glycoprotein ◽  
Infection Models ◽  
New Strategies

ABSTRACT New strategies are needed to combat antibiotic resistance, especially against pathogens such as methicillin-resistant Staphylococcus aureus. A tick antifreeze glycoprotein, IAFGP, possesses potent antibiofilm properties against a variety of clinical pathogens, including S. aureus. Synergy between IAFGP, or a peptide (P1) representative of a repeat region of the protein, with different antibiotics was assessed in vitro. Antibiotics that synergized with either IAFPG or P1 were further evaluated in vivo using vertebrate and invertebrate infection models. IAFGP readily enhanced the efficacy of antibiotics against S. aureus. Synergy with daptomycin, an antibiotic used to treat methicillin-resistant S. aureus, was observed in vitro and in vivo using iafgp-transgenic mice and flies. Furthermore, synergy with ciprofloxacin or gentamicin, antibiotics not generally used to treat S. aureus, was also perceived. The combined effect of the antibiotic and IAFGP was associated with improved permeation of the antibiotic into the cell. Our results highlight that synergy of IAFGP with antibiotics traditionally used to treat this pathogen, and enhancement of the potency of antibiotics not commonly used against this microbe, can provide novel alternative therapeutic strategies to combat bacterial infections.

scholarly journals In VitroActivities of Daptomycin-, Vancomycin-, and Teicoplanin-Loaded Polymethylmethacrylate against Methicillin-Susceptible, Methicillin-Resistant, and Vancomycin-Intermediate Strains of Staphylococcus aureus

2011 ◽  
Vol 55 (12) ◽  
pp. 5480-5484 ◽  
Author(s):  
Yuhan Chang ◽  
Wen-Chien Chen ◽  
Pang-Hsin Hsieh ◽  
Dave W. Chen ◽  
Mel S. Lee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
High Performance ◽  
Low Dose ◽  
Antibacterial Activities ◽  
High Dose ◽  
Bone Cements ◽  
Antibacterial Effects ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTThe objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptibleStaphylococcus aureus(MSSA), methicillin-resistantStaphylococcus aureus(MRSA), and vancomycin-intermediateStaphylococcus aureus(VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated usingin vitrobroth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against differentStaphylococcus aureusstrains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment ofStaphylococcus aureusinfection, teicoplanin was superior in terms of antibacterial effects.

scholarly journals Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

2015 ◽  
Vol 59 (12) ◽  
pp. 7571-7580 ◽  
Author(s):  
Wei-Tao Jia ◽  
Qiang Fu ◽  
Wen-Hai Huang ◽  
Chang-Qing Zhang ◽  
Mohamed N. Rahaman
Keyword(s):  
Staphylococcus Aureus ◽  
Bioactive Glass ◽  
Calcium Sulfate ◽  
Rabbit Model ◽  
Local Delivery ◽  
Methicillin Resistant ◽  
Content Type ◽  
Borate Bioactive Glass ◽  
Phosphate Buffered Saline

ABSTRACTThere is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TECin vitroand to cure methicillin-resistantStaphylococcus aureus(MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC.

scholarly journals Emergence of Linezolid-Resistant Mutants in a Susceptible-Cell Population of Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 55 (5) ◽  
pp. 2466-2468 ◽  
Author(s):  
Yurika Ikeda-Dantsuji ◽  
Hideaki Hanaki ◽  
Taiji Nakae ◽  
Yoshio Takesue ◽  
Kazunori Tomono ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Population ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Rrna Genes ◽  
Chloramphenicol Resistance ◽  
Methicillin Resistant ◽  
Content Type ◽  
Susceptible Cell ◽  
Linezolid Therapy ◽  
Resistant Mutants

ABSTRACTMethicillin-resistantStaphylococcus aureuswith a MIC of linezolid of 4 μg/ml, isolated from a patient who had undergone unsuccessful linezolid therapy, yielded linezolid-resistant mutants in blood agar at 48 h of incubation. The resistant clones showed a MIC of linezolid ranging from 8 to 64 μg/ml and accumulated the T2500A mutation(s) of the rRNA genes. Emergence of these resistant clones appears to be facilitated by a cryptic mutation or mutations associated with chloramphenicol resistance.

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