Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 90
Filter
1.
Can J Microbiol ; 70(7): 252-261, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38855942

ABSTRACT

Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by Mycobacterium aurum. The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in M. aurum infected MDMs, as well as the production of defb4, IL-1ß, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1ß, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.


Subject(s)
Cytokines , Drug Repositioning , Histone Deacetylase Inhibitors , Immunity, Innate , Mycobacterium Infections, Nontuberculous , Immunity, Innate/drug effects , Humans , Mycobacterium Infections, Nontuberculous/immunology , Mycobacterium Infections, Nontuberculous/microbiology , Histone Deacetylase Inhibitors/pharmacology , Cytokines/metabolism , Macrophages/immunology , Macrophages/drug effects , Macrophages/microbiology , Nontuberculous Mycobacteria/drug effects , Nontuberculous Mycobacteria/immunology , Mycobacterium/immunology , Mycobacterium/drug effects
2.
Future Med Chem ; 16(7): 679-688, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38390753

ABSTRACT

Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.


Subject(s)
Cymenes , Microbial Sensitivity Tests , Mycobacterium , Cymenes/pharmacology , Cymenes/chemistry , Mycobacterium/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Molecular Docking Simulation , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry
3.
Cells ; 10(4)2021 04 12.
Article in English | MEDLINE | ID: mdl-33921194

ABSTRACT

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1ß, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.


Subject(s)
Decitabine/pharmacology , Immunity , Macrophages/immunology , Monocytes/immunology , Biomarkers/metabolism , DNA Methylation/drug effects , Granuloma/pathology , Humans , Immunity/drug effects , Inflammation/pathology , Macrophages/drug effects , Macrophages/microbiology , Monocytes/drug effects , Monocytes/microbiology , Mycobacterium/drug effects , Phenotype
4.
Nat Prod Res ; 35(5): 802-806, 2021 Mar.
Article in English | MEDLINE | ID: mdl-30990070

ABSTRACT

Colletia paradoxa (Spreng.) Esc. (Rhamnaceae, Colletieae) is a medicinal plant, threatened with extinction in Brazil, presenting great morphological variability. Our objective is to investigate the phytochemical components, antioxidant capacity and antimycobacterial activity of different morphotypes of C. paradoxa in different environments. For this, the crude extract of the leaves and branches of the individuals sampled was used. The elimination capacity of the free radicals was determined by the DPPH method, the antimycobacterial activity by the broth microdilution method and the phenolic content by the spectrophotometric method using the Folin-Ciocalteu reagent and by HPLC. The extracts of C. paradoxa and its morphotypes showed significant amounts of phenolic compounds, including quercetin, quercitrin and rutin, besides considerable antioxidant and antimycobacterial activity No connection was detected between the phytochemical composition and different morphotypes of C. paradoxa.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Mycobacterium/drug effects , Phytochemicals/analysis , Phytochemicals/pharmacology , Rhamnaceae/chemistry , Anti-Bacterial Agents/analysis , Antioxidants/chemistry , Brazil , Chromatography , Chromatography, High Pressure Liquid , Flavonoids/chemistry , Microbial Sensitivity Tests , Plant Leaves/chemistry
5.
Biometals ; 33(4-5): 269-282, 2020 10.
Article in English | MEDLINE | ID: mdl-32980947

ABSTRACT

Rapidly growing mycobacteria (RGM) are pathogens that belong to the mycobacteriaceae family and responsible for causing mycobacterioses, which are infections of opportunistic nature and with increasing incidence rates in the world population. This work evaluated the use of six water-soluble cationic porphyrins as photosensitizers for the antimicrobial photodynamic therapy (aPDT) of four RGM strains: Mycolicibacterium fortuitum, Mycolicibacterium smeagmatis, Mycobacteroides abscessus subs. Abscessus, and Mycobacteroides abscessus subsp. massiliense. Experiments were conducted with an adequate concentration of photosensitizer under white-light irradiation conditions over 90 min and the results showed that porphyrins 1 and 2 (M = 2H or ZnII ion) were the most effective and significantly reduced the concentration of viable mycobacteria. The present work shows the result is dependent on the metal-center ion coordinated in the cationic porphyrin core. Moreover, we showed by atomic force microscopy (AFM) the possible membrane photodamage caused by reactive oxygen species and analyzed the morphology and adhesive force properties. Tetra-positively charged and water-soluble metalloporphyrins may be promising antimycobacterial aPDT agents with potential applications in medical clinical cases and bioremediation.


Subject(s)
Coordination Complexes/pharmacology , Metals, Heavy/pharmacology , Mycobacterium/drug effects , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Cations/chemistry , Cations/pharmacology , Coordination Complexes/chemistry , Metals, Heavy/chemistry , Molecular Structure , Mycobacterium/growth & development , Photochemical Processes , Photosensitizing Agents/chemistry , Porphyrins/chemistry , Solubility , Water/chemistry
6.
Microb Pathog ; 144: 104203, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32304794

ABSTRACT

Several species of rapidly growing mycobacteria (RGM) have been associated with biofilms in areas such as biomedical devices, water distribution systems, cosmetic surgery, and catheter-related blood infections. Biofilms which exhibit antimicrobial resistance such as those formed by the genus Mycobacterium pose a significant risk to health and are of particular interest to researchers. Licarin A (a neolignan found in numerous plant species e.g. nutmeg) has been reported to show a wide range of biological actions including anti-inflammatory, antioxidant, and antibacterial properties. The aim of this study was to prepare a set of Licarin A derivatives and investigate the impact of specific structural changes on its antimycobacterial ability, and its effect on the biofilm formation of RGM species. Initially, the phenolic sub-unit and alkenyl side chain of Licarin A were modified to create derivatives with a higher partition coefficient; as the activity of a compound against mycobacteria seems to be strongly influenced by its hydrophobicity. Further, polar groups were inserted into the side chain to change the hydrophilic-lipophilic profile of the molecules. Results showed variability in the susceptibility profile of mycobacteria against the Licarin A derivatives under analysis. A number of the derivatives showed significant inhibitory activity of planktonic growth of the three strains of mycobacteria used, with even lower MIC values than those observed with reference drugs and Licarin A itself. Cytotoxicity assays showed they also have low toxicity, confirming that structural modifications to the Licarin A have made improvements to its antimycobacterial properties.


Subject(s)
Biofilms/drug effects , Lignans/chemistry , Lignans/pharmacology , Mycobacterium/drug effects , Nontuberculous Mycobacteria/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Clarithromycin/pharmacology , Microbial Sensitivity Tests , Myristica/chemistry , Nontuberculous Mycobacteria/physiology , Sulfamethoxazole/pharmacology
7.
Tuberculosis (Edinb) ; 117: 45-51, 2019 07.
Article in English | MEDLINE | ID: mdl-31378267

ABSTRACT

This manuscript reports, at the first time, the photoinactivation evaluation of tetra-cationic and anionic porphyrins as photosensitizers (PS) for the photodynamic inactivation (PDI) of rapidly growing mycobacteria strains. Two different charged porphyrin groups were obtained commercially. PDI experiments in the strains Mycobacterium massiliense e Mycobacterium fortuitum conducted with adequate concentration (without aggregation) of photosensitizer under white light at a fluence rate of 50 mW/cm2 over 90 min showed that the most effective PS caused a 100 times reduction in the concentration of viable mycobacteria. The present results show that porphyrin with positively charge are more efficient PS than anionic porphyrin (negatively charged) against M. massiliense e M. fortuitum. It is also clear that the effectiveness of the molecule as PS for PDI studies with mycobacteria is strongly related with the porphyrin peripheral charge, and consequently their solubility in physiological media. Cationic PSs might be promising anti-mycobacteria PDI agents with potential applications in medical clinical cases and bioremediation.


Subject(s)
Mycobacterium/drug effects , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Anions , Cations , Colony Count, Microbial , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Humans , Light , Microbial Sensitivity Tests/methods , Microbial Viability/drug effects , Microbial Viability/radiation effects , Mycobacterium/physiology , Mycobacterium/radiation effects , Mycobacterium abscessus/drug effects , Mycobacterium abscessus/physiology , Mycobacterium abscessus/radiation effects , Mycobacterium fortuitum/drug effects , Mycobacterium fortuitum/physiology , Mycobacterium fortuitum/radiation effects , Reactive Oxygen Species/metabolism
8.
Benef Microbes ; 10(3): 315-328, 2019 Apr 19.
Article in English | MEDLINE | ID: mdl-30773930

ABSTRACT

Bacteriocins are bacterially-produced antimicrobial peptides that have killing activity principally against other relatively closely-related bacteria. Some bacteriocins of the lactic acid bacteria (LAB) have for many years been extensively applied in food biopreservation. However, especially during the last decade, a number of reports have appeared about unanticipated extensions to the generally rather narrow anti-bacterial activity spectrum of some of the LAB bacteriocins and novel applications have been proposed for bacteriocins ranging from controlling the growth of an increasingly-heterogeneous variety of pathogens, including Gram-negative multidrug resistant bacteria, viruses, yeasts, and in particular, difficult to control Mycobacterium spp., to their potential application as anticancer agents. How best can we assess this now rapidly-accumulating stream of reports on potential future applications of bacteriocins? Where is the line between realistic, science-based proposals and highly-speculative fiction and what are the 'critical points' that might help us to draw this line? In this review, we have attempted to analyse a selection of the presently-available data concerning relatively 'unorthodox' (i.e. beyond food preservation) applications of bacteriocins, and, by utilising our set of 'critical points', we endeavour to identify essential or/and missing information that appear crucial for success of the proposed applications.


Subject(s)
Bacteriocins/pharmacology , Lactobacillales/chemistry , Anti-Bacterial Agents , Antifungal Agents , Antineoplastic Agents , Antiviral Agents , Bacteriocins/biosynthesis , Food Preservatives , Mycobacterium/drug effects , Mycobacterium/growth & development , Nisin/pharmacology , Quorum Sensing
9.
Biofouling ; 34(8): 893-911, 2018 09.
Article in English | MEDLINE | ID: mdl-30418037

ABSTRACT

Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with biofilm formation. In this context, this work aimed to evaluate the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on rapidly growing mycobacteria (RGM), as well as to evaluate their safety through cytotoxic assays. The results demonstrate potentiation of the novel compounds in antibiofilm activity, mainly in the complex with Au, which was able to completely inhibit biofilm formation and had the capacity to destroy the biofilm at all the concentrations tested. All cytotoxic data suggest that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives, as well as safe molecules, which could be used as potential therapeutic agents for bacterial and biofilm elimination.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Metals/chemistry , Mycobacterium/drug effects , Sulfamethoxazole/analogs & derivatives , Sulfamethoxazole/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms/growth & development , Humans , Microbial Sensitivity Tests , Mycobacterium/physiology , Sulfamethoxazole/chemistry
10.
Int J Mycobacteriol ; 7(2): 122-127, 2018.
Article in English | MEDLINE | ID: mdl-29900886

ABSTRACT

Background: : There is evidence that drinking water could be a source of infections with pathogenic nontuberculous mycobacteria (NTM) potentially risky to human health. The aim was to investigate the resistance of two NTM isolated from drinking water, Mycobacterium gordonae and Mycobacterium chubuense, at different concentrations of chlorine (as sodium hypochlorite), used in drinking water sanitation. Methods: : The NTM were grown in suspension and in biofilms and were challenged with biocide for 10 and 60 min. Results: To obtain 7-log reduction from the initial population of M. chubuense, in the planktonic state, there were necessary 20 ppm of chorine and 60 min of exposure. The same effect was achieved in M. gordonae with 10 ppm for the same period. The maximum reduction of both NTM in biofilm was 3-log reduction and was achieved using 30 ppm for 60 min. The chlorine susceptibility of cells in biofilms was significantly lower than that of planktonic cells. The results highlight the resistance of both NTM to the concentrations used in routine water sanitation (0.2 ppm according to Argentine Food Code). Differences in chlorine resistance found between the two NTM in planktonic growth decrease when they are grown in biofilm. Conclusion: This suggests that current water disinfection procedures do not always achieve effective control of NTM in the public supply system, with the consequent health risk to susceptible population, and the need to take into account biofilms, because of their deep consequences in the way to analyze the survival of prokaryotic cells in different environments.


Subject(s)
Biofilms/drug effects , Disinfectants/pharmacology , Mycobacterium/drug effects , Nontuberculous Mycobacteria/drug effects , Sodium Hypochlorite/pharmacology , Disinfection , Mycobacterium/growth & development , Mycobacterium/physiology , Nontuberculous Mycobacteria/growth & development , Nontuberculous Mycobacteria/physiology , Plankton/drug effects , Plankton/physiology
11.
Toxins (Basel) ; 10(6)2018 05 30.
Article in English | MEDLINE | ID: mdl-29848960

ABSTRACT

Mycobacterium massiliense is a rapid growing, multidrug-resistant, non-tuberculous mycobacteria that is responsible for a wide spectrum of skin and soft tissue infections, as well as other organs, such as the lungs. Antimicrobial peptides had been described as broad-spectrum antimicrobial, chemotactic, and immunomodulator molecules. In this study we evaluated an antimicrobial peptide derived from scorpion Tityus obscurus as an anti-mycobacterial agent in vitro and in vivo. Bioinformatics analyses demonstrated that the peptide ToAP2 have a conserved region similar to several membrane proteins, as well as mouse cathelicidin. ToAP2 inhibited the growth of four M. massiliense strains (GO01, GO06, GO08, and CRM0020) at a minimal bactericidal concentration (MBC) of 200 µM. MBC concentration used to treat infected macrophages was able to inhibit 50% of the bacterial growth of all strains. ToAP2 treatment of infected mice with bacilli reduced the bacterial load in the liver, lung, and spleen, similarly to clarithromycin levels (90%). ToAP2 alone recruited monocytes (F4/80low Gr1), neutrophils (F4/80- Gr1), and eosinophils (F4/80+ Gr1+). ToAP2, together with M. massiliense infection, was able to increase F4/80low and reduce the percentage of F4/80high macrophages when compared with infected and untreated mice. ToAP2 has in vitro anti-microbial activity that is improved in vivo due to chemotactic activity.


Subject(s)
Anti-Bacterial Agents/toxicity , Antimicrobial Cationic Peptides/toxicity , Mycobacterium/drug effects , Scorpions , Animals , Anti-Bacterial Agents/therapeutic use , Leukocytes/drug effects , Leukocytes/immunology , Liver/drug effects , Liver/microbiology , Lung/drug effects , Lung/microbiology , Macrophages/microbiology , Mice, Inbred BALB C , Mice, Knockout , Mycobacterium/growth & development , Mycobacterium Infections/drug therapy , Mycobacterium Infections/microbiology , Spleen/drug effects , Spleen/microbiology
12.
Arch. argent. pediatr ; 116(3): 463-467, jun. 2018. ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-950028

ABSTRACT

La tuberculosis, considerada desde 2003 por la Organización Mundial de la Salud una emergencia global de salud, provoca una mortalidad anual de alrededor de 2 millones de personas, fundamentalmente, en países en vías de desarrollo. En la población pediátrica española, la incidencia es de 5 casos/100 000 niños de entre 5 y 14 años y 13 casos/100 000 niños de entre 0 y 4 años. La infección se transmite por vía respiratoria por enfermos bacilíferos. Los niños eliminan escasos bacilos en secreciones respiratorias y no suelen transmitir la infección. En España, el porcentaje de resistencias a isoniazida en la población general es de 5% y es superior en la población inmigrante, lo cual es importante tener en cuenta para el tratamiento de los casos. Se presenta un caso de tuberculosis por Mycobacterium africanum multirresistente al tratamiento, con evolución satisfactoria posterior a la terapia múltiple.


Tuberculosis, considered since 2003 by the World Health Organization a global health emergency, causes annual mortality of approximately 2 million people, mainly in developing countries. In the Spanish pediatric population, the incidence is 5 cases/100 000 children between 5 and 14 years and 13 cases/100 000 children between 0 and 4 years. The infection is transmitted through the respiratory tract by baciliferous patients. Children eliminate few bacilli in respiratory secretions and do not usually transmit the infection. In Spain, the resistance to isoniazid in the general population is 5%, being higher in the immigrant population, which is important to take into account for the treatment of cases. A case of tuberculosis due to Mycobacterium africanum multiresistant to treatment is presented, with satisfactory evolution after multiple therapy.


Subject(s)
Humans , Female , Child, Preschool , Tuberculosis, Multidrug-Resistant/diagnosis , Mycobacterium/isolation & purification , Antitubercular Agents/administration & dosage , Treatment Outcome , Mycobacterium/drug effects , Antitubercular Agents/pharmacology
13.
Arch Argent Pediatr ; 116(3): e463-e467, 2018 06 01.
Article in Spanish | MEDLINE | ID: mdl-29756725

ABSTRACT

Tuberculosis, considered since 2003 by the World Health Organization a global health emergency, causes annual mortality of approximately 2 million people, mainly in developing countries. In the Spanish pediatric population, the incidence is 5 cases/100 000 children between 5 and 14 years and 13 cases/100 000 children between 0 and 4 years. The infection is transmitted through the respiratory tract by baciliferous patients. Children eliminate few bacilli in respiratory secretions and do not usually transmit the infection. In Spain, the resistance to isoniazid in the general population is 5%, being higher in the immigrant population, which is important to take into account for the treatment of cases. A case of tuberculosis due to Mycobacterium africanum multiresistant to treatment is presented, with satisfactory evolution after multiple therapy.


La tuberculosis, considerada desde 2003 por la Organización Mundial de la Salud una emergencia global de salud, provoca una mortalidad anual de alrededor de 2 millones de personas, fundamentalmente, en países en vías de desarrollo. En la población pediátrica española, la incidencia es de 5 casos/100 000 niños de entre 5 y 14 años y 13 casos/100 000 niños de entre 0 y 4 años. La infección se transmite por vía respiratoria por enfermos bacilíferos. Los niños eliminan escasos bacilos en secreciones respiratorias y no suelen transmitir la infección. En España, el porcentaje de resistencias a isoniazida en la población general es de 5% y es superior en la población inmigrante, lo cual es importante tener en cuenta para el tratamiento de los casos. Se presenta un caso de tuberculosis por Mycobacterium africanum multirresistente al tratamiento, con evolución satisfactoria posterior a la terapia múltiple.


Subject(s)
Antitubercular Agents/administration & dosage , Mycobacterium/isolation & purification , Tuberculosis, Multidrug-Resistant/diagnosis , Antitubercular Agents/pharmacology , Child, Preschool , Female , Humans , Mycobacterium/drug effects , Spain , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology
14.
Folia Microbiol (Praha) ; 63(4): 499-505, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29497981

ABSTRACT

Antibiotic-resistant bacteria have been observed with increasing frequency over the past decades, driving the search for new drugs and stimulating the interest in natural products sources. Endophytic fungi from medicinal plants represent a great source of novel bioactive compounds useful to pharmaceutical and agronomical purposes. Diaporthe terebinthifolii is an endophytic species isolated from Schinus terebinthifolius, a plant used in popular medicine for several health problems. The strain D. terebinthifolii LGMF907 was previously reported by our group to produce secondary metabolites with biological activity against phytopathogens. Based on these data, strain LGMF907 was chosen for bioprospecting against microorganisms of clinical importance and for characterization of major secondary metabolites. In this study, different culture conditions were evaluated and the biological activity of this strain was expanded. The crude extracts demonstrated high antibacterial activity against Escherichia coli, Micrococcus luteus, Saccharomyces cerevisiae, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant S. aureus. The compounds diaporthin and orthosporin were characterized and also showed activity against the clinical microorganisms evaluated. This study discloses the first isolation of diaporthin and orthosporin from D. terebinthifolii, and revealed the potential of this endophytic fungus to produce secondary metabolites with antimicrobial activity.


Subject(s)
Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Bacteria/drug effects , Bioprospecting , Saccharomyces cerevisiae/drug effects , Saccharomycetales/metabolism , Anti-Infective Agents/chemistry , Culture Media , Endophytes/chemistry , Endophytes/metabolism , Escherichia coli/drug effects , Fermentation , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium/drug effects , Saccharomycetales/chemistry , Staphylococcus aureus/drug effects
16.
Mem Inst Oswaldo Cruz ; 112(11): 775-778, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29091138

ABSTRACT

BACKGROUND: Mycobacterium abscessus complex (MABC) includes species with high resistance rates among mycobacterial pathogens. In fact, MABC infections may not respond to clarithromycin treatment, which has historically been very effective against MABC infection. Molecular markers have been proposed to detect both acquired (rrl polymorphisms) and inducible (erm(41) polymorphisms) clarithromycin resistance in MABC isolates. OBJECTIVES: This study aimed to evaluate the susceptibility profile and molecular markers of clarithromycin resistance in MABC. METHODS: The clarithromycin susceptibility profile was determined by broth microdilution with reads on days 3, 5, 7 and 14. Mutations in the rrl and erm(41) genes were evaluated by polymerase chain reaction (PCR) using specific primers, followed by sequencing. FINDINGS: A total of 14 M. abscessus subsp. abscessus isolates and 28 M. abscessus subsp. massiliense isolates were evaluated, and clarithromycin resistance was observed in all isolates for up to three days of incubation. None of the 42 isolates exhibited a point mutation in the rrl gene, while all the isolates had a T28 polymorphism in the erm(41) gene. Moreover, all 28 M. abscessus subsp. massiliense isolates had a deletion in the erm(41) gene. MAIN CONCLUSIONS: While all the MABC isolates exhibited acquired clarithromycin resistance, no isolates exhibited a point mutation in the rrl gene in this study. The M. abscessus subsp. massiliense isolates demonstrated clarithromycin resistance, which is an uncommon phenotype. The molecular data for the rrl and erm(41) genes were not consistent with the phenotypic test results of clarithromycin susceptibility, indicating a lack of correlation between molecular clarithromycin resistance markers for both acquired and inducible resistance.


Subject(s)
Anti-Bacterial Agents/pharmacology , Clarithromycin/pharmacology , Drug Resistance, Bacterial/genetics , Mutation/genetics , Mycobacterium/drug effects , Mycobacterium/genetics , Drug Resistance, Bacterial/drug effects , Genes, Bacterial/genetics , Humans , Microbial Sensitivity Tests
17.
Mem. Inst. Oswaldo Cruz ; 112(11): 775-778, Nov. 2017. tab
Article in English | LILACS | ID: biblio-894846

ABSTRACT

BACKGROUND Mycobacterium abscessus complex (MABC) includes species with high resistance rates among mycobacterial pathogens. In fact, MABC infections may not respond to clarithromycin treatment, which has historically been very effective against MABC infection. Molecular markers have been proposed to detect both acquired (rrl polymorphisms) and inducible (erm(41) polymorphisms) clarithromycin resistance in MABC isolates. OBJECTIVES This study aimed to evaluate the susceptibility profile and molecular markers of clarithromycin resistance in MABC. METHODS The clarithromycin susceptibility profile was determined by broth microdilution with reads on days 3, 5, 7 and 14. Mutations in the rrl and erm(41) genes were evaluated by polymerase chain reaction (PCR) using specific primers, followed by sequencing. FINDINGS A total of 14 M. abscessus subsp. abscessus isolates and 28 M. abscessus subsp. massiliense isolates were evaluated, and clarithromycin resistance was observed in all isolates for up to three days of incubation. None of the 42 isolates exhibited a point mutation in the rrl gene, while all the isolates had a T28 polymorphism in the erm(41) gene. Moreover, all 28 M. abscessus subsp. massiliense isolates had a deletion in the erm(41) gene. MAIN CONCLUSIONS While all the MABC isolates exhibited acquired clarithromycin resistance, no isolates exhibited a point mutation in the rrl gene in this study. The M. abscessus subsp. massiliense isolates demonstrated clarithromycin resistance, which is an uncommon phenotype. The molecular data for the rrl and erm(41) genes were not consistent with the phenotypic test results of clarithromycin susceptibility, indicating a lack of correlation between molecular clarithromycin resistance markers for both acquired and inducible resistance.


Subject(s)
Humans , Clarithromycin/pharmacology , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Mutation/genetics , Mycobacterium/drug effects , Mycobacterium/genetics , Microbial Sensitivity Tests , Genes, Bacterial
18.
Epidemiol Infect ; 145(14): 3020-3034, 2017 10.
Article in English | MEDLINE | ID: mdl-28903800

ABSTRACT

The purpose of this study was to develop a method for identifying newly diagnosed tuberculosis (TB) patients at risk for TB adverse events in Tamaulipas, Mexico. Surveillance data between 2006 and 2013 (8431 subjects) was used to develop risk scores based on predictive modelling. The final models revealed that TB patients failing their treatment regimen were more likely to have at most a primary school education, multi-drug resistance (MDR)-TB, and few to moderate bacilli on acid-fast bacilli smear. TB patients who died were more likely to be older males with MDR-TB, HIV, malnutrition, and reporting excessive alcohol use. Modified risk scores were developed with strong predictability for treatment failure and death (c-statistic 0·65 and 0·70, respectively), and moderate predictability for drug resistance (c-statistic 0·57). Among TB patients with diabetes, risk scores showed moderate predictability for death (c-statistic 0·68). Our findings suggest that in the clinical setting, the use of our risk scores for TB treatment failure or death will help identify these individuals for tailored management to prevent these adverse events. In contrast, the available variables in the TB surveillance dataset are not robust predictors of drug resistance, indicating the need for prompt testing at time of diagnosis.


Subject(s)
Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Mycobacterium/drug effects , Public Health/methods , Tuberculosis/drug therapy , Adult , Aged , Female , Humans , Male , Mexico/epidemiology , Middle Aged , Treatment Failure , Tuberculosis/microbiology , Tuberculosis/mortality , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/mortality , Young Adult
19.
J Inorg Biochem ; 172: 138-146, 2017 07.
Article in English | MEDLINE | ID: mdl-28463762

ABSTRACT

Five new copper(II) complexes of the type [Cu(NO)(NN)(ClO4)2], in which NO=4-fluorophenoxyacetic acid hydrazide (4-FH) or 4-nitrobenzoic hydrazide (4-NH) and NN=1,10-phenanthroline (phen), 4-4'-dimethoxy-2-2'-bipyridine (dmb) or 2,2-bipyridine (bipy) were synthesized and characterized using various spectroscopic methods. The X-ray structural analysis of one representative compound indicates that the geometry around the copper ion is distorted octahedron, in which the ion is coordinated to hydrazide via the terminal nitrogen and the carbonyl oxygen, and to heterocyclic bases via their two nitrogen atoms. Two perchlorate anions occupy the apical positions, completing the coordination sphere. The cytotoxic activity of compounds was investigated in three tumor cell lines (K562, MDA-MB-231 and MCF-7). Concerning K562 cell line, the complexes with 1,10-phenanthroline exhibit high cytotoxic activity and are more active than carboplatin, free ligands and [Cu(phen)2]2+. Considering the cytotoxicity results, further investigations for the compounds [Cu(4-FH)(phen)(ClO4)2] I and [Cu(4-NH)(phen)(ClO4)2]∙H2O III were performed. Flow cytometric analysis revealed that these complexes induce apoptotic cell death in MDA-MB-231 cell line and bind to DNA with K values of 4.38×104 and 2.62×104, respectively. These compounds were also evaluated against wild type Mycobacterium tuberculosis (ATCC 27294) and exhibited antimycobacterial activity, displayed MIC values lower than those of the corresponding free ligands.


Subject(s)
Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Copper/chemistry , Heterocyclic Compounds/chemistry , Hydrazines/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cell Line, Tumor , Coordination Complexes/chemistry , Crystallography, X-Ray , Female , Humans , Inhibitory Concentration 50 , K562 Cells , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium/drug effects
20.
Microb Drug Resist ; 23(3): 294-300, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27429159

ABSTRACT

The objectives of this study were to determine the kinetic parameters of purified recombinant BlaMab and BlaMmas by spectrophotometry, analyze the genetic environment of the blaMab and blaMmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that BlaMab and BlaMmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. BlaMmas hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. BlaMab and BlaMmas showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A ß-lactamases by the presence of a more flexible Ω loop, which could impact in the hydrolysis efficiency against some antibiotics. A -35 consensus sequence (TCGACA) and embedded at the 3' end of MAB_2874, which may constitute the blaMab and blaMmas promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of ß-lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.


Subject(s)
Mycobacterium/genetics , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Catalysis/drug effects , Consensus Sequence/genetics , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Hydrolysis/drug effects , Kinetics , Microbial Sensitivity Tests/methods , Mycobacterium/drug effects , Mycobacterium Infections/drug therapy , Mycobacterium Infections/microbiology , Promoter Regions, Genetic/drug effects , Promoter Regions, Genetic/genetics
SELECTION OF CITATIONS
SEARCH DETAIL