Venom-derived peptide Mastoparan-1 eradicates planktonic and biofilm-embedded methicillin-resistant Staphylococcus aureus isolates.

During the past decade, cationic antimicrobial peptides (CAPs) have gained particular interest among researchers, since they often display broad-spectrum antimicrobial activity and low possibility of resistance emergence. This study aimed to investigate in vitro effectiveness of Mastoparan-1 (MP-1), a tetradecapeptide CAP from hornet venom, against methicillin-resistant Staphylococcus aureus (MRSA) isolates. MP-1 had a high propensity to form alpha-helix based on structural predictions. MP-1 was found to possess strong antimicrobial activities and weak cytotoxic effects. Multiple treatments of MRSA with MP-1 at sub-lethal dose did not induce resistance. At 4 × minimum bactericidal concentration (MBC), MP-1 eradicated bacteria within 60 min, whereas vancomycin was unable to eradicate MRSA even after 480 min of exposure, highlighting rapid bactericidal kinetics of MP-1. Treatment of bacteria with 2 × MBC of MP-1 caused a time-dependent increase in orange/red fluorescence intensity. Compared with vancomycin, MP-1 significantly reduced biofilm formation and diminished both biofilm biomass and viability of biofilm-embedded bacteria in a concentration-dependent manner. Taken together, the current data reveal not only that MP-1 is a potent bactericidal and antibiofilm agent, but also that it is less likely to invoke antimicrobial resistance, reinforcing further studies concerning the therapeutic applications of MP-1.

Naphtho[1,2-b]furan-4,5-dione is a potent anti-MRSA agent against planktonic, biofilm and intracellular bacteria.

AIM: Naphtho[1,2-b]furan-4,5-dione (N12D) and naphtho[2,3-b]furan-4,9-dione (N23D) are furanonaphthoquinone derivatives from natural resources. We examined the antimicrobial activity of N12D and N23D against drug-resistant Staphylococcus aureus. MATERIALS & METHODS: Minimum inhibitory concentration, minimum bactericidal concentration, bacterial viability and agar diffusion assay were conducted against methicillin-resistant S. aureus (MRSA) and clinical isolates of vancomycin-resistant S. aureus. RESULTS & CONCLUSION: The minimum inhibitory concentration of N12D and N23D against MRSA was 4.9-9.8 and 39 µM, respectively. With regard to the agar diffusion test, the inhibition zone of the quinone compounds was threefold larger than that of oxacillin. N12D was found to inhibit MRSA biofilm thickness from 24 to 16 µm as observed by confocal microscopy. N12D showed a significant reduction of the intracellular MRSA burden without decreasing the macrophage viability. The antibacterial mechanisms of N12D may be bacterial wall/membrane damage and disturbance of gluconeogenesis and the tricarboxylic acid cycle.

Arylthiazole antibiotics targeting intracellular methicillin-resistant Staphylococcus aureus (MRSA) that interfere with bacterial cell wall synthesis.

The promising antibacterial potency of arylthiazole antibiotics is offset by their limited activity against intracellular bacteria (namely methicillin-resistant Staphylococcus aureus (MRSA)), similar to many clinically-approved antibiotics. The failure to target these hidden pathogens is due to the compounds' lack of proper characteristics to accumulate intracellularly. Fine tuning of the size and polar-surface-area of the linking heteroaromatic ring provided a new series of 5-thiazolylarylthiazoles with balanced properties that allow them to sufficiently cross and accumulate inside macrophages infected with MRSA. The most promising compound 4i exhibited rapid bactericidal activity, good metabolic stability and produced over 80% reduction of intracellular MRSA in infected macrophages.

Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin.

This investigation aimed to study the in vivo harmful effects of the subcutaneous injection of different methicillin resistance Staphylococcus aureus extracts (MRSA2, MRSA4, MRSA10, MRSA69, MRSA70, MRSA76, and MRSA78). Such strains represented the highest minimum inhibition concentration toward methicillin with various multidrug-resistant patterns. The obtained results revealed that rats injected with the MRSA4 extract died immediately after the last dose indicating the high cytotoxicity of MRSA4 strain (100% mortality). While the mortalities in other groups injected by the other MRSA extracts ranged from 50 to 75%. In comparison with the normal animal group, all MRSA extracts induced a hepatotoxic effect which was indicated from the significant (p < 0.01) increases in the activities of the serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) enzymes. Moreover, alkaline phosphatase (ALP) combined with a partial nephrotoxicity that was monitored from the significant elevation of serum urea concentration. While serum creatinine levels did not affect. Similarly, a significant elevation was recorded in serum levels of tumor biomarkers (alpha fetoprotein; AFP, carcinoembryonic antigen; CEA, and lactate dehydrogenase; LDH) reflecting their carcinogenic potential. On the other hand, the percentage of micronuclei (MN) in polychromatic erythrocytes from bone marrow cells was statistically significant in all groups as compared to the control group. The percentage of sperm abnormalities was statistically significant compared to the control. Different types of head abnormalities and coiled tail were recorded. Consequently, the current study focused on fighting MRSA virulence factors by the new compound ayamycin, which proved to be potent anti-virulence factor against all MRSA strains under study by significant decreasing of their streptokinase activities, hemolysin synthesis, biofilm formation, and their cell surface hydrophobicity.

Random peptide mixtures inhibit and eradicate methicillin-resistant Staphylococcus aureus biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is a biofilm-forming pathogen that can cause serious health complications in humans, ranging from minor to life-threatening infections. The challenge of successfully combating biofilms requires the discovery of compounds with a novel mode of action. We have recently developed sequence-random hydrophobic-cationic peptides that display a broad antibacterial activity. In the current study we show that our novel compounds are capable of controlling and managing MRSA biofilms and might be used as lead biofilm inhibitor candidates for further studies.

Synthesis, characterization, and evaluation of antibacterial effect of Ag nanoparticles against Escherichia coli O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA).

Silver nanoparticles (AgNPs) have been shown great interest because of their potential antibacterial effect. Recently, this has been increased due to resistance in some pathogenic bacteria strains to conventional antibiotics, which has initiated new studies to search for more effective treatments against resistant microorganisms. For these reasons, AgNPs have become an important approach for applications in nanobiotechnology in the development of antibiotic treatment of different bacterial infections. This study was aimed at synthesizing AgNPs using cysteine as a reducer agent and cetyl-tri-methyl-ammonium bromide as a stabilizer in order to obtain more efficient treatment against the pathogen bacteria Escherichia coli O157:H7. These AgNPs were characterized through UV-Vis spectroscopy, transmission electron microscopy, and dynamic light scattering. From these analyses, formation of spherical nanoparticles with an average size of 55 nm was confirmed. Finally, minimal inhibitory concentration (MIC) and minimal bactericide concentration (MBC) of these AgNPs against pathogenic strains E. coli O157:H7 and methicillin-resistant Staphylococcus aureus (MRSA) were determined in both solid and liquid media. MIC and MBC values were around 0.25 µg/mL and 1 µg/mL, respectively. These parameters were comparable to those reported in the literature and were even more effective than other synthesized AgNPs.

3-Anhydro-6-hydroxy-ophiobolin A, a new sesterterpene inhibiting the growth of methicillin-resistant Staphylococcus aureus and inducing the cell death by apoptosis on K562, from the phytopathogenic fungus Bipolaris oryzae.

A new ophiobolin derivative, 3-anhydro-6-hydroxy-ophiobolin A (1), as well as two known ophiobolin derivatives 3-anhydro-ophiobolin A (2) and 3-anhydro-6-epi-ophiobolin A (3) were isolated from the PDB culture of a phytopathogenic fungus Bipolaris oryzae. The structure of 1 was elucidated through 2D NMR and other spectroscopic techniques. Compound 1 exhibited strong antimicrobial activity against Bacille Calmette-Guerin, Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus with MIC value of 12.5 µg/mL, and potent antiproliferative activity against cell lines HepG2 and K562 with IC50 of 6.49 µM and 4.06 µM, respectively. Further studies on the cytotoxicity of compound 1 against K562 cells demonstrated that it induced apoptosis, observed by flow cytometric method. Preliminary structure-activity relationships of these ophiobolins and the mechanism of apoptosis induced by 1 were analyzed.

Antimicrobial activity of silica coated silicon nano-tubes (SCSNT) and silica coated silicon nano-particles (SCSNP) synthesized by gas phase condensation.

Silica-coated, silicon nanotubes (SCSNTs) and silica-coated, silicon nanoparticles (SCSNPs) have been synthesized by catalyst-free single-step gas phase condensation using the arc plasma process. Transmission electron microscopy and scanning tunneling microscopy showed that SCSNTs exhibited a wall thickness of less than 1 nm, with an average diameter of 14 nm and a length of several 100 nm. Both nano-structures had a high specific surface area. The present study has demonstrated cheaper, resistance-free and effective antibacterial activity in silica-coated silicon nano-structures, each for two Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) was estimated, using the optical densitometric technique, and by determining colony-forming units. The MIC was found to range in the order of micrograms, which is comparable to the reported MIC of metal oxides for these bacteria. SCSNTs were found to be more effective in limiting the growth of multidrug-resistant Staphylococcus aureus over SCSNPs at 10 µg/ml (IC 50 = 100 µg/ml).

Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA.

Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus.

AIMS: The objectives of this study were to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic-resistant Staphylococcus aureus strains. METHODS AND RESULTS: The inhibitory effect of commercial orange essential oil (EO) against six Staph. aureus strains was tested using disc diffusion and agar dilution methods. The mechanism of EO action on MRSA was analysed by transcriptional profiling. Morphological changes of EO-treated Staph. aureus were examined using transmission electron microscopy. Results showed that 0·1% of terpeneless cold-pressed Valencia orange oil (CPV) induced the cell wall stress stimulon consistent with the inhibition of cell wall synthesis. Transmission electron microscopic observation revealed cell lysis and suggested a cell wall lysis-related mechanism of CPV. CONCLUSIONS: CPV inhibits the growth of Staph. aureus, causes gene expression changes consistent with the inhibition of cell wall synthesis, and triggers cell lysis. SIGNIFICANCE AND IMPACT OF THE STUDY: Multiple antibiotics resistance is becoming a serious problem in the management of Staph. aureus infections. In this study, the altered expression of cell wall-associated genes and subsequent cell lysis in MRSA caused by CPV suggest that it may be a potential antimicrobial agent to control antibiotic-resistant Staph. aureus.