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1.
Vaccine ; 41 Suppl 2: S41-S52, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-37951694

RESUMEN

Group B streptococcus (GBS) is a major global cause of neonatal meningitis, sepsis and pneumonia, with an estimated 91,000 infant deaths per year and an additional 46,000 stillbirths. GBS infection in pregnancy is also associated with adverse maternal outcomes and preterm births. As such, the World Health Organization (WHO) prioritised the development of a GBS vaccine suitable for use in pregnant women and use in LMICs, where the burden of disease is highest. Several GBS vaccines are in clinical development. The WHO Defeating Meningitis by 2030 has set a target of 2026 for vaccine licensure. This 'Vaccine Value Profile' (VVP) for GBS is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO regions of AFR, AMR, EUR, WPR. All contributors have extensive expertise on various elements of the GBS VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.


Asunto(s)
Meningitis , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Lactante , Recién Nacido , Embarazo , Femenino , Humanos , Complicaciones Infecciosas del Embarazo/prevención & control , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae
2.
J Cachexia Sarcopenia Muscle ; 12(6): 1393-1407, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34523250

RESUMEN

BACKGROUND: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia. METHODS: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed. RESULTS: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota. CONCLUSIONS: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.


Asunto(s)
Microbioma Gastrointestinal , Sarcopenia , Simbióticos , Anciano , Animales , Trasplante de Microbiota Fecal , Femenino , Humanos , Masculino , Ratones , Prebióticos , Sarcopenia/etiología , Sarcopenia/terapia
3.
BMC Infect Dis ; 21(1): 578, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34130629

RESUMEN

BACKGROUND: Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings. This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study. METHODS: A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI). Three (3) genes that are responsible for ESBL production; blaCTX-M, blaSHV, and blaTEM were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR. RESULTS: A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was blaCTX-M (n = 36), while 16 isolates had blaTEM and 7 had blaSHV. Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive. CONCLUSIONS: A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana , Universidades , Adulto , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Carbapenémicos/uso terapéutico , Estudios de Cohortes , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Femenino , Humanos , Klebsiella/aislamiento & purificación , Infecciones por Klebsiella/microbiología , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Sri Lanka , Infecciones Estafilocócicas/microbiología , Estudiantes , Adulto Joven , beta-Lactamasas/genética
4.
Bone Joint Res ; 10(1): 51-59, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33448869

RESUMEN

AIMS: The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. METHODS: Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. RESULTS: A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. CONCLUSION: Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: Bone Joint Res 2021;10(1):51-59.

5.
Curr Med Chem ; 28(21): 4283-4294, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33292110

RESUMEN

BACKGROUND: We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups. METHODS: The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two mutant strains [AAC(6')-APH(2") and RN4220/pUL5054], and ten nonduplicate clinical strains of hospital- and community-associated MRSA. Upon light irradiation, the minimum bactericidal concentrations of compound 3 were in the range of 1.56-50 µM against all the sixteen MRSA strains. Interestingly, compound 3 was not only more active than an analogue in which the ammonium groups are not directly connected to the n-conjugated system (compound 4), but also showed significantly higher (p < 0.05) antibacterial potency than the clinically approved photosensitizer methylene blue. The skin irritation of compound 3 during topical application was tested on human 3-D skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM. In the murine MRSA infected wound study, the colony forming unit reduction of compound 3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log10) compared to other test groups except for the positive control. CONCLUSION: In conclusion, the present study provides a scientific basis for future development of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA wound infection.


Asunto(s)
Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Fotoquimioterapia , Animales , Antibacterianos/farmacología , Boro , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/uso terapéutico , Porfobilinógeno/análogos & derivados
6.
J Crohns Colitis ; 12(8): 954-962, 2018 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-29757355

RESUMEN

BACKGROUND: Biologic therapies have revolutionised the treatment of immune-mediated diseases including inflammatory bowel disease [IBD] and rheumatological disorders. However, biologic treatments are associated with an increased risk of reactivation of latent tuberculosis. Data from regular monitoring for latent tuberculosis infection [LTBI] during biologic treatment are lacking. METHODS: Consecutive patients eligible for biologic therapies were screened for LTBI and prospectively followed up for 3 years. Incidence and risk factors of latent tuberculosis tests conversion (interferon gamma release assays [IGRA], tuberculin skin tests [TST], and chest radiography [CXR]) with clinical outcomes were studied. RESULTS: A total of 108 patients [83 IBD; 25 rheumatological disorders] were included. At baseline, 18/108 [16.7%] patients [five IBD; 13 rheumatological disorders] were tested positive for LTBI. Of these, 14/18 [77.8%] patients received isoniazid monotherapy for 9 months. Of the remainder, 17/90 [18.9%] patients had LTBI test conversion while on biologic therapies and of these 14/17 [82.4%] received isoniazid monotherapy for 9 months. Age, sex, smoking status, alcohol use, travel history, disease type, and immunosuppressive therapy were not associated with LTBI test conversion. In subjects with IGRA conversion, serial IGRA levels normalised after completion of isoniazid except in one patient whose IGRA remained persistently elevated despite isoniazid and who subsequently developed active TB. CONCLUSIONS: Conversion of LTBI is common and occurred early during biologic therapy in an area with intermediate TB burden. Subjects with latent TB tests conversion and persistently high IGRA levels may have an increased risk of TB reactivation or development of active TB, and they require close observation or intensive workup for active TB.


Asunto(s)
Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Enfermedades Reumáticas/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Antirreumáticos/uso terapéutico , Antituberculosos/uso terapéutico , Terapia Biológica , Femenino , Fármacos Gastrointestinales/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Ensayos de Liberación de Interferón gamma , Isoniazida/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía Torácica , Enfermedades Reumáticas/inmunología , Factores de Riesgo , Prueba de Tuberculina , Adulto Joven
7.
J Trop Pediatr ; 64(5): 403-408, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-29126217

RESUMEN

Aim: Pneumococcus is a common commensal and an important pathogen among children for which immunization is available. Some serotypes occasionally cause severe pneumococcal disease with high mortality and morbidity. We reviewed all pneumococcal serotypes and mortality/morbidity in a pediatric intensive care unit (PICU) following universal pneumococcal conjugate vaccine (PCV) immunization. Methods: A 13-valent PCV was introduced in the universal immunization program in late 2011 in Hong Kong. We retrospectively reviewed all pneumococcal serotypes in the pre-(2007-11) and post-(2012-16) 13-valent PCV era. Results: There were 29 (1.9%) PICU patients with pneumococcal isolation, of which 6 died (20% motality). Serogroups 6 and 19 predominated before and Serogroup 3 after 2012. In the post-13-valent PCV era, the prevalence of pneumococcus isolation in PICU was increased from 1 to 2% (p = 0.04); Serogroup 3 was the major serotype of morbidity, despite supposedly under vaccine coverage. The majority of pneumococcus were penicillin-sensitive (94%) in the post 13-valent PCV era. All pneumococcus specimens were sensitive to cefotaxime and vancomycin. Binary logistic regression showed that there were reductions in Serogroup 6 (odds ratio [OR], 0.050; 95% confidence interval [CI], 0.004-0.574; p = 0.016) and Serogroup 19 (odds ratio [OR], 0.105; 95% confidence interval [CI], 0.014-0.786; p = 0.028) but not mortality or morbidity for patients admitted after 2012. Conclusions: SPD is associated with significant morbidity and mortality, despite treatment with systemic antibiotics and ICU support. The expanded coverage of 13-valent PCV results in the reduction of Serotypes 6 and 19 but not mortality/morbidity associated with SPD in the setting of a PICU.


Asunto(s)
Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/aislamiento & purificación , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología , Niño , Preescolar , Femenino , Hong Kong/epidemiología , Humanos , Lactante , Masculino , Morbilidad , Programas Nacionales de Salud , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/inmunología , Prevalencia , Serogrupo , Streptococcus pneumoniae/inmunología , Vacunación
8.
J Dermatolog Treat ; 29(3): 235-237, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29098912

RESUMEN

BACKGROUND: In a series of bench and clinical trials, our group has determined the immunologic effects and clinical efficacy of a concoction of five herbal ingredients (PentaHerbs Formula, PHF) in treating children with atopic eczema (AE). This study investigates the antimicrobial effects that may be induced with PHF treatment. METHODS: We investigated the effects of PHF on the minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Staphylococcus aureus and various bacteria that are commonly present on the skin of patients with AE. RESULTS: Staphylococcus aureus ATCC 25923, Methicllin resistant Staphylococcus aureus (MRSA) ATCC BAA-43, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Enterobacter cloacae ATCC 13047, Proteus vulgaris ATCC 6380, and Acinetobacter baumannii ATCC 19606 were tested. PHF was more effective against Staphylococcus aureus ATCC 25923 and Methicllin resistant Staphylococcus aureus (MRSA) ATCC BAA-43. MIC and MBC were 1 and 25 mg/mL, respectively. CONCLUSION: PHF was more effective against Staphylococcus aureus ATCC 25923 and Methicllin resistant Staphylococcus aureus (MRSA) ATCC BAA-43t. PHF may be developed into a Staphylococcus aureus targeting topical application.


Asunto(s)
Antiinfecciosos/farmacología , Medicamentos Herbarios Chinos/farmacología , Bacterias Grampositivas/efectos de los fármacos , Antiinfecciosos/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Medicamentos Herbarios Chinos/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos
9.
Biochemistry ; 56(38): 5049-5052, 2017 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-28782938

RESUMEN

We report the discovery of the first bacterial ribosomal RNA (rRNA) synthesis inhibitor that has specific antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). A pharmacophore model was constructed on the basis of the protein-protein interaction between essential bacterial rRNA transcription factors NusB and NusE and employed for an in silico screen to identify potential leads. One compound, (E)-2-{[(3-ethynylphenyl)imino]methyl}-4-nitrophenol (MC4), demonstrated antimicrobial activity against a panel of S. aureus strains, including MRSA, without significant toxicity to mammalian cells. MC4 resulted in a decrease in the rRNA level in bacteria, and the target specificity of MC4 was confirmed at the molecular level. Results obtained from this work validated the bacterial rRNA transcription machinery as a novel antimicrobial target. This approach may be extended to other factors in rRNA transcription, and MC4 could be applied as a chemical probe to dissect the relationship among MRSA infection, MRSA growth rate, and rRNA synthesis, in addition to its therapeutic potential.


Asunto(s)
Antibacterianos/farmacología , Hidrazonas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Nitrofenoles/farmacología , ARN Ribosómico/antagonistas & inhibidores , Antibacterianos/efectos adversos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Simulación por Computador , Evaluación Preclínica de Medicamentos/métodos , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Hidrazonas/química , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Nitrofenoles/química , Conformación Proteica , ARN Ribosómico/biosíntesis , ARN Ribosómico/genética , Proteínas Ribosómicas/química , Proteínas Ribosómicas/metabolismo , Factores de Transcripción/química , Factores de Transcripción/metabolismo
10.
Vaccine ; 34(33): 3867-74, 2016 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-27265449

RESUMEN

OBJECTIVES: Pneumococcal conjugate vaccine (PCV) has been included in Hong Kong's Childhood Immunization Programme since 2009. This study aimed to assess nasopharyngeal pneumococcal carriage rate, serotypes and antimicrobial resistance pattern in young children after the introduction of 13-valent PCV (PCV13). STUDY DESIGN: A community-based, cross-sectional surveillance study was performed on healthy infants attending eleven Maternal and Child Health Centres across different parts of Hong Kong. Nasopharyngeal swabs were obtained from healthy children aged 2, 12 and 18months during their visit to the centers for immunization from June 2013 to June 2014. Pneumococcal isolates were serotyped and tested for antimicrobial resistance. Details of the demographics, family composition, vaccination history and medical history was obtained through interview of the guardians. RESULTS: 1541 children were recruited. The overall carriage rate was 5.5%. Children aged 12 and 18months were more likely to have pneumococcal colonization (12months OR: 2.88; 95% CI: 1.41-5.87 and 18months OR: 2.19, 95% CI: 1.05-4.57). Recent respiratory symptoms and presence of siblings younger than 6years were independently associated with pneumococcal carriage. Eighty-four pneumococcal isolates were serotyped. The most prevalent serogroup/types were 15 (15B/C, 16.7%; 15A/F, 9.5%), 6C (15.5%) and 23A (13.1%). Overall, 2.4% of the isolates were heptavalent PCV serotypes, 10.7% were PCV13 serotypes and 89.3% were non-PCV13 serotypes. The proportions of penicillin, cefotaxime and erythromycin non-susceptible isolates were 7.3%, 13.4% and 79.3% respectively. CONCLUSION: The rate of pneumococcal carriage was low in young children in Hong Kong and compared to previous local studies there appears to have been an overall reduction in the carriage rate after the introduction of PCV. Likely serotype replacement was noted with a predominance of non-vaccine serotypes in pneumococcal carriage with the emergence of serogroup/type 15 and 6C.


Asunto(s)
Portador Sano/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae/clasificación , Portador Sano/microbiología , Femenino , Hong Kong/epidemiología , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Nasofaringe/microbiología , Serogrupo
11.
Diagn Microbiol Infect Dis ; 81(1): 66-70, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25445117

RESUMEN

Serogroup 15 pneumococcal isolates from nasopharyngeal carriage of hospitalized children admitted to a teaching hospital in Hong Kong from April 2009 to September 2013 were characterized by pulse-field gel electrophoresis (PFGE), multilocus sequence typing, and antimicrobial non-susceptibility testing. The overall proportion of serogroup 15 isolates in the pre-PCV7 and post-PCV13 periods rose from 5.7% to 20.0%. The increase in trend for serotype 15B/C was statistically significant among children presented with pneumonia; bronchiolitis; upper respiratory tract infection; and febrile, non-respiratory diseases and for serotype 15A/F, among children with bronchiolitis and febrile, non-respiratory diseases. The predominant PFGE cluster of serotype 15B/C belonged to sequence type (ST) 199. Replacement of this more susceptible cluster (Ery and Tet non-susceptibilities of 32.2% and 25.4%) with the non-susceptible cluster, ST8859 (Ery and Tet non-susceptibilities of 91.7% and 87.5%) was noted. ST63 was the predominant serotype 15A cluster (Ery and Tet non-susceptibilities of 97.4% and 92.3%). Serogroup 15 subtypes have emerged in the post-PCV13 era, and these non-susceptible clusters warrant closer monitoring as candidates for incorporation to future pneumococcal vaccines.


Asunto(s)
Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/uso terapéutico , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/genética , Vacunas Conjugadas/uso terapéutico , Adolescente , Bronquiolitis/microbiología , Niño , Preescolar , Electroforesis en Gel de Campo Pulsado , Hong Kong , Humanos , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Infecciones Neumocócicas/prevención & control , Neumonía Estafilocócica/microbiología , Serogrupo , Streptococcus pneumoniae/aislamiento & purificación
12.
J Pharm Pharmacol ; 67(1): 107-16, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25212982

RESUMEN

OBJECTIVES: The aims of this study were to identify the active ingredients from Portulaca oleracea L. (PO) that could provide synergism with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and their possible mechanisms of resistance inhibition. METHODS: High-speed counter-current chromatography (HSCCC) coupled with gas chromatography-mass spectrometry and a panel of laboratory MRSA strains were used for checkerboard and efflux inhibitory assays. KEY FINDINGS: Linoleic and oleic acids were identified from HSCCC fraction 18 of PO with synergistic antibacterial activity when combined with erythromycin against RN4220/pUL5054. Ethidium bromide efflux inhibitory studies revealed that linoleic and oleic acids may interfere the activity of MsrA pump. By comparing among a panel of linoleic and oleic acids analogues, unsaturated fatty acids in salt form with cis configuration and an increase in number of double bonds were found to further increase the antibacterial activity when used alone or in combination with antibiotics. CONCLUSION: This study reported for the first time that two active ingredients, namely linoleic and oleic acids, were identified from PO with synergistic antibacterial activity when combined with erythromycin against MRSA RN4220/pUL5054 and possibly act by inhibiting the efflux pumps of the bacteria cells.


Asunto(s)
Antibacterianos/farmacología , Eritromicina/farmacología , Ácido Linoleico/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ácido Oléico/farmacología , Portulaca , Ciprofloxacina/farmacología , Sinergismo Farmacológico , Quimioterapia Combinada , Cromatografía de Gases y Espectrometría de Masas , Ácido Linoleico/química , Pruebas de Sensibilidad Microbiana , Ácido Oléico/química , Extractos Vegetales/química
13.
Phytomedicine ; 20(7): 611-4, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23541215

RESUMEN

Increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) worldwide with limited therapeutic options is a growing public health concern. Natural products have been shown to possess antibacterial actions against MRSA. Flavonoids from natural products have been shown to possess antibacterial actions against MRSA by antagonizing its resistance mechanisms. Diosmin and diosmetin are natural flavonoids found in a variety of citrus fruits. The aim of this study was to investigate whether diosmin and diosmetin could inhibit the growth of MRSA and the in vitro enzymatic activity of a newly discovered MRSA drug target, pyruvate kinase (PK). By using a panel of MRSA strains with known resistant mechanisms, neither diosmin nor diosmetin was shown to possess direct antibacterial activities against all tested MRSA strains. However, in checkerboard assay, we found that diosmetin together with erythromycin, could synergistically inhibit the growth of ABC-pump overexpressed MRSA-RN4220/pUL5054, and time kill assay also showed that the antibacterial activities of diosmetin with erythromycin were bactericidal. Diosmetin was further shown to significantly suppress the MRSA PK activities in a dose dependent manner. In conclusion, the inhibition of MRSA PK by diosmetin could lead to a deficiency of ATP and affect the bacterial efflux pump which might contribute to the antibacterial actions of diosmetin against MRSA.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antibacterianos/farmacología , Eritromicina/farmacología , Flavonoides/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Piruvato Quinasa/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Diosmina/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Staphylococcus aureus Resistente a Meticilina/metabolismo , Pruebas de Sensibilidad Microbiana
14.
Artículo en Inglés | MEDLINE | ID: mdl-22177235

RESUMEN

Bacterial resistance to antibiotics has become a serious problem of public health that concerns almost all currently used antibacterial agents and that manifests in all fields of their application. To find more antibacterial agents from natural resources is all the time considered as an important strategy. Sophora flavescens is a popularly used antibacterial herb in Chinese Medicine, from which prenylated flavones were reported as the antibacterial ingredients but with a major concern of toxicity. In our screening on the antibacterial activities of various chemicals of this herb, 18 fractions were obtained from 8 g of 50% ethanol extract on a preparative high-speed counter-current chromatography (HSCCC, 1000 ml). The system of n-hexane/ethyl acetate/methanol/water (1:1:1:1) was used as the two-phase separation solvent. A chalcone named kuraridin was isolated from the best anti-MRSA fraction, together with sophoraflavanone G, a known active ingredient of S. flavescens. Their structures were elucidated by analysis of the NMR spectra. Both compounds exhibited significant anti-MRSA effects, compared to baicalein that is a well known anti-MRSA natural product. More important, kuraridin showed no toxicity on human peripheral blood mononuclear cells (PBMC) at the concentration up to 64 µg/ml while sophoraflavanone G inhibited over 50% of cellular activity at 4 µg/ml or higher concentration. These data suggested that opening of ring A of the prenylated flavones might decrease the toxicity and remain the anti-MRSA effect, from a viewpoint of structure-activity relationship.


Asunto(s)
Antibacterianos/aislamiento & purificación , Chalconas/aislamiento & purificación , Distribución en Contracorriente/métodos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Monoterpenos/aislamiento & purificación , Sophora/química , Antibacterianos/química , Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , Chalconas/química , Chalconas/farmacología , Cromatografía Líquida de Alta Presión , Flavanonas/química , Flavanonas/aislamiento & purificación , Flavanonas/farmacología , Humanos , Leucocitos Mononucleares , Pruebas de Sensibilidad Microbiana , Monoterpenos/química , Monoterpenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química
15.
J Ethnopharmacol ; 137(1): 767-73, 2011 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-21782012

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of ß-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms. MATERIAL AND METHODS: A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities of baicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined. RESULTS: In the checkerboard dilution test and time-kill assay, baicalein at 16 µg/ml could synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner. CONCLUSION: Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Ciprofloxacina/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Flavanonas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Piruvato Quinasa/antagonistas & inhibidores , Proteínas Bacterianas/genética , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Staphylococcus aureus Resistente a Meticilina/enzimología , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Piruvato Quinasa/metabolismo , Factores de Tiempo , Regulación hacia Arriba
17.
J Natl Med Assoc ; 100(7): 797-800, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18672556

RESUMEN

INTRODUCTION: Staphylococcus aureus colonization/infection is commonly associated with disease severity in children with atopic dermatitis. The present report is a three-year retrospective chart review of five cases (comprising three boys and two girls, aged 9-15 years at referral) of methicillin-resistant S. aureus (MRSA) in children with moderate-to-severe atopic dermatitis. The review period spanned 2004-2007. All had longstanding severe disease, high IgE and eosinophil counts. Generalized erythema and a peculiar fishy odor were frequently observed by parents and physicians when MRSA was isolated during some of the episodes of exacerbation. All had tried various combinations of topical and systemic steroids, topical immunomodulants, traditional Chinese medicine and courses of antibiotics-without lasting relief. All specimens of MRSA had in-vitro sensitivity to vancomycin, with corresponding clinical correlates of disappearance of the erythema and fishy odor. CONCLUSION: A fishy odor and facial/generalized erythema in a patient with atopic dermatitis should alert the physician to screen for MRSA. The organism is rarely isolated, even among children with moderate-to-severe atopic dermatitis, and is usually sensitive to vancomycin.


Asunto(s)
Dermatitis Atópica/complicaciones , Resistencia a la Meticilina , Infecciones Estafilocócicas/diagnóstico , Staphylococcus aureus/aislamiento & purificación , Adolescente , Niño , Femenino , Humanos , Masculino , Estudios Retrospectivos , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico
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