Sasitorn Chusri

Enhancing antibiotic activity: a strategy to control Acinetobacter infections

OBJECTIVES The emergence of antibiotic resistance has seriously diminished antibiotic efficacy and an increasing number of infections are becoming difficult to treat. One approach to the restoration of antibiotic activity is to administer them in conjunction with non-antibiotic compounds that depress resistance mechanisms. We describe the activity of ellagic and tannic acids as adjuvants that enhance the activity of aminocoumarin antibiotics against multidrug-resistant (MDR) Acinetobacter baumannii. METHODS Adjuvant activity of plant phenolics was tested using growth inhibition assays in combination with subinhibitory concentrations of novobiocin. The antibacterial susceptibilities of susceptible and MDR A. baumannii to a variety of antibiotics were determined in the absence and presence of ellagic and tannic acids. The effect of the adjuvants on bacterial outer membrane function was examined by using the fluorescence dye 1-N-phenylnaphthylamine (NPN). The efflux pump inhibition was measured by the intracellular accumulation of ethidium bromide (EtBr) and pyronin Y. RESULTS At 40 microM, ellagic and tannic acids enhanced the activity of novobiocin, coumermycin, chlorobiocin, rifampicin and fusidic acid against A. baumannii. There were no increases in the uptake of NPN or in the accumulation of EtBr after strains were treated with these adjuvants; however, the intracellular accumulation of pyronin Y by the treated cells was significantly increased, suggesting that ellagic and tannic acids act as efflux pump inhibitors. CONCLUSIONS Susceptibility of MDR A. baumannii to a variety of antibiotics was enhanced in the presence of ellagic and tannic acids. The use of such plant compounds might provide effective treatments for resistant Gram-negative bacterial infections.

Thai ethnomedicinal plants as resistant modifying agents for combating Acinetobacter baumannii infections.

AbstractsBackgroundAcinetobacter baumannii is well-recognized as an important nosocomial pathogen, however, due to their intrinsic resistance to several antibiotics, treatment options are limited. Synergistic effects between antibiotics and medicinal plants, particularly their active components, have intensively been studied as alternative approaches.MethodsFifty-one ethanol extracts obtained from 44 different selected medicinal plant species were tested for resistance modifying agents (RMAs) of novobiocin against A. baumannii using growth inhibition assay.ResultsAt 250 μg/ml, Holarrhena antidysenterica, Punica granatum, Quisqualis indica, Terminalia bellirica, Terminalia chebula, and Terminalia sp. that possessed low intrinsic antibacterial activity significantly enhanced the activity of novobiocin at 1 μg/ml (1/8xminimum inhibitory concentration) against this pathogen. Holarrhena antidysenterica at 7.8 μg/ml demonstrated remarkable resistant modifying ability against A. baumannii in combination with novobiocin. The phytochemical study revealed that constituents of this medicinal plant contain alkaloids, condensed tannins, and triterpenoids.ConclusionThe use of Holarrhena antidysenterica in combination with novobiocin provides an effective alternative treatment for multidrug resistant A. baumannii infections.

Detailed studies on Quercus infectoria Olivier (nutgalls) as an alternative treatment for methicillin‐resistant Staphylococcus aureus infections

Aims:  To investigate the antimethicillin‐resistant Staphylococcus aureus (MRSA) mechanism of Quercus infectoria (nutgalls) extract and its components.

Anti-biofilm activity of Quercus infectoria G. Olivier against methicillin-resistant Staphylococcus aureus

Aims:  To establish the effect of Quercus infectoria G. Olivier extract and its main constituent, tannic acid, on staphylococcal biofilm and their anti‐biofilm mechanisms.

Quercus infectoria: a candidate for the control of methicillin-resistant Staphylococcus aureus infections.

Acetone, ethyl acetate, 95% ethanol and aqueous extracts of Quercus infectoria (Q. infectoria) demonstrated significant antibacterial activities against all strains of methicillin‐resistant Staphylococcus aureus (MRSA) and methicillin‐susceptible Staphylococcus aureus (MSSA). Inhibition zones were in the range 11.75–16.82 mm. Both MRSA and MSSA strains exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values at 0.13 and 0.13–1.00 mg/mL, respectively. At 2 MIC, the growth of two representative MRSA strains was continually inhibited for at least 20 h. Surviving MRSA cells were not detected within 12–14 h after treatment with the extract at 4 MIC concentration. Staphylococcus aureus ATCC 25923 demonstrated similar results. Copyright

Thai Herbal Formulas Used for Wound Treatment: A Study of Their Antibacterial Potency, Anti-Inflammatory, Antioxidant, and Cytotoxicity Effects

AIM This present work was aimed to investigate wound healing-related biologic activities of traditional herbal formulas used for wound treatment in southern Thailand. METHODS Water and ethanol extracts of the formulas (THR-SK004, THR-SK010, and THR-SK011) were tested for their antibacterial potency against methicillin-resistant Staphylococcus aureus (MRSA) and -susceptible S. aureus. Anti-inflammatory activities of the extracts were assessed by detection of the inhibition of lipopolysaccharide-induced nitric oxide production. Anti-oxidant activities and cytotoxicity of the extracts were also measured. RESULTS Among the tested formulas, ethanol extract of THR-SK010 consisting of four herbs: Curcuma longa L., Areca catechu L., Oryza sativa L., and Garcinia mangostana L., was found to possess promising antibacterial activities with MIC90 of 4 μg mL(-1) against MRSA isolates. This ethanol extract offered the highest anti-inflammatory activity as well as DPPH and hydroxyl radical scavenging activities. CONCLUSIONS Remarkable antibacterial, anti-inflammatory, and antioxidant activities as well as low toxicity on Vero cells of THR-SK010 ethanol extract provide scientific information to support the topical use of the formula for wound treatment. This information proposes the potential to develop a new generation of phytopharmaceuticals based on traditional knowledge.

Holarrhena antidysenterica as a resistance modifying agent against Acinetobacter baumannii: Its effects on bacterial outer membrane permeability and efflux pumps

Increasing rates of infections caused by multidrug resistant Acinetobacter baumannii (MDRAB) and extensively drug resistant A. baumannii (XDRAB) have caused the need for searching alternative agents. The purposed of this project was to search plant-derived natural products that act as resistant modifying agents (RMAs) against A. baumannii. In this study, we further evaluated the activity of Holarrhena antidysenterica that has been previously proposed as RMA of novobiocin for a model strain, A. baumannii ATCC 19606 on clinically isolated non-MDRAB, MDRAB, and XDRAB. Effects of H. antidysenterica on outer membrane permeability and efflux pumps of the pathogen were conducted to preliminary elucidate mechanisms of this resistant modifier. Novobiocin was selected as a model antibiotic because it is well-established as an effective agent against Gram-positive pathogens. But, it possessed low level of antibacterial activity against Gram-negative pathogens due to an effective permeability barrier of these pathogens. H. antidysenterica ethanol extract possessed weak intrinsic antibacterial activity with minimum inhibitory concentration (MIC) more than 1000 μg/mL. The extract, at concentrations of 250, 125, and 62.5 μg/mL, remarkably enhanced the inhibitory effects of novobiocin (1/4 × MIC; 1-4 μg/mL) against XDRAB isolates. Synergistic effects of novobiocin at 1/4 × MIC and 1/8 × MIC in combination with H. antidysenterica either at 31.2, 15.6, or 7.8 μg/mL against clinical isolates non-MDRAB, MDRAB, and XDRAB were evidenced for 80% of the combinations (189 out of 234 combinations). Although, no enhancement of the accumulation of ethidium bromide was observed after treated with H. antidysenterica, this plant extract weakened the outer membrane of the pathogen as indicated by an increase in the N-phenyl-1-naphthylamine uptake. Our results suggested that H. antidysenterica which primarily interrupts membrane permeability should be further investigated as a promising resistant modifier for A. baumannii.

Inhibition of microbial adhesion to plastic surface and human buccal epithelial cells by Rhodomyrtus tomentosa leaf extract.

OBJECTIVE The adherence of oral pathogenic microorganisms to host tissues is the initial step for successful process of oral diseases. This study aimed to determine the effect of the Rhodomyrtus tomentosa leaf extract and rhodomyrtone, an antibacterial compound from R. tomentosa leaf, on adhesion of some oral pathogens to polystyrene plastic surface and human buccal epithelial cells. METHODS The minimum inhibitory concentration (MIC) was evaluated using broth microdilution method. The microbial adhesion to the plastic surface and buccal cells was determined using microtiter plate method and microscopy technique. RESULTS The ethanol extract of leaf demonstrated antibacterial activity against oral microorganisms including Staphylococcus aureus ATCC 25923, Streptococcus mutans (clinical isolate), and Candida albicans ATCC 90028 with the MIC values of 31.25, 15.62, and 1000μg/ml, respectively. Rhodomyrtone displayed activity with the MIC values of 0.78 and 0.39μg/ml against S. aureus ATCC 25923 and S. mutans, respectively. The MIC value of the compound against C. albicans ATCC 90028 was more than 100μg/ml which was the highest test concentration. All pathogenic microorganisms treated with the extract and rhodomyrtone at their subinhibitory concentrations resulted in a decrease in their adherence ability to both plastic surface and buccal cells. CONCLUSION It is suggested that R. tomentosa extract and rhodomyrtone may be useful in therapy or as prophylaxis in infections involving oral pathogens.

Quercus infectoria. Oliv.

Abstract Bacterial resistance to antibiotics is enhanced by unrestricted use of such drugs. In addition, stimulating effects of certain antibiotics on the production of verocytotoxin by enterohemorrhagic Escherichia coli. have been reported. The aim of this communication was to report a medicinal plant species that is effective against a broad range of bacteria of clinical importance including Acinetobacter baumannii., Bacillus cereus., Enterobacter faecalis., Escherichia coli., Helicobacter pylori., Klebsiella pneumoniae., Listeria monocytogenes., Pseudomonas aeruginosa., Salmonella. spp., Shigella flexneri., Staphylococcus aureus., Streptococcus mutans., and Streptococcus pyogenes.. Ethanol extracts of Quercus infectoria. Oliv. (Fagaceae) demonstrate a broad spectrum of activity against all bacterial species tested. Detailed studies were carried out on clinical isolates of pathogens commonly presenting problems with the use of antibiotics, including enterohemorrhagic Escherichia coli. (EHEC), methicillin-resistant Staphylococcus aureus. (MRSA), multidrug-resistant Klebsiella pneumoniae., multidrug-resistant Helicobacter pylori., and Salmonella.spp. The extracts of Quercus infectoria. displayed remarkable activity against MRSA with MICs ranging from 0.02 to 0.4 mg/mL, and MBCs ranging from 0.4 to 1.6 mg/mL. More importantly, this plant species could exhibit strong antibacterial activity against all Gram-Negative organisms. Its significant activity was shown with EHEC, with MICs of 0.05 to 0.1 mg/mL and MBCs of 0.8 to 1.6 mg/mL. The results from this study indicate that Quercus infectoria. is potentially a good source of antibacterial substances with broad spectrum of activities against antibiotic-resistant bacteria.

Synergistic effects of ethnomedicinal plants of Apocynaceae family and antibiotics against clinical isolates of Acinetobacter baumannii

OBJECTIVE To investigate the efficacy of 17 ethnomedicinal plants belonging to Apocynaceae family used in combination with 16 conventional antibiotics against non-multidrug resistant-, multidrug resistant (MDR)-, and extensive drug resistant (XDR) Acinetobacter baumannii (A. baumannii). METHODS Antibacterial activity and resistance modifying ability of 272 combinations were determined by growth inhibition assays and further confirmed by time-kill assay. RESULTS Among the combinations of the antibiotics with Apocynaceae ethanol extracts on this pathogen, 15 (5%) had synergistic effects, 23 (8%) had partial synergistic effects and 234 (86%) had no effects. Synergistic activity was observed mostly when the Apocynaceae extracts were combined with rifampicin or cefazolin. Interestingly, 10 out of 17 combinations between the extracts and rifampicin displayed synergistic or partial synergistic behaviors. Holarrhena antidysenterica extract was additionally tested to restore rifampicin activity against clinical isolates of MDR and XDR A. baumannii. With respect to total or partial synergy, 70% was XDR A. baumannii isolates and 66% was MDR A. baumannii isolates. CONCLUSIONS Holarrhena antidysenterica extract clearly demonstrated the ability to restore rifampicin activity against both A. baumannii ATCC19606 and clinically isolated A. baumannii. Additional studies examining its active principles as well as mechanisms of actions such as the effects on efflux pumps and outer membrane permeability alterations are recommended.