25 results on '"Molicotti, Paola"'
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2. Use of bedaquiline in spinal osteomyelitis and soft tissue abscess caused by multidrug-resistant Mycobacterium tuberculosis: A case report.
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De Vito A, Fiore V, Urru V, Bozzi E, Geremia N, Princic E, Canu D, Molicotti P, Are R, Babudieri S, and Madeddu G
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- Abscess drug therapy, Adult, Amikacin pharmacology, Amikacin therapeutic use, Antitubercular Agents adverse effects, Diarylquinolines pharmacology, Diarylquinolines therapeutic use, Humans, Linezolid pharmacology, Male, Moxifloxacin pharmacology, Moxifloxacin therapeutic use, Off-Label Use, Rifabutin pharmacology, Rifabutin therapeutic use, Young Adult, Mycobacterium tuberculosis, Osteomyelitis drug therapy, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Spinal chemically induced, Tuberculosis, Spinal diagnostic imaging, Tuberculosis, Spinal drug therapy
- Abstract
Introduction: Spinal Tuberculosis (STB) represents between 1% and 2% of total tuberculosis cases. STB management remains challenging; the first-line approach consists of medical treatment, while surgery is reserved for patients with complications. No data regarding STB treatment with bedaquiline-containing regimens are available in the literature., Case Description: Herein, we report the case of a 21-year-old man from Côte d'Ivoire with a multidrug resistance STB with subcutaneous abscess. After approval of the hospital off-label drug committee, we started bedaquiline 400 mg daily for two weeks, followed by 200 mg three times per week, for 22 weeks, associated with linezolid 600 mg daily, rifabutin 450 mg daily, and amikacin 750 mg daily (interrupted after eight weeks). During treatment, we performed a weekly EKG. No QT prolongation was shown, but inverted T waves appeared, requiring several cardiological consultations and cardiac MRI, but no cardiac dysfunction was found. After 24 weeks, bedaquiline was replaced with moxifloxacin 400 mg daily. The patient continued treatment for another year. We performed another computer tomography at the end of treatment, confirming the cure., Discussion: A salvage regimen containing bedaquiline proved effective in treating multidrug-resistance tuberculosis spinal infection without causing severe adverse effects. However, further studies are needed to evaluate better bedaquiline bone penetration and the correct duration of treatment with bedaquiline in MDR spinal tuberculosis., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier España, S.L.U.)
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- 2022
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3. The bifunctional protein GlmU is a key factor in biofilm formation induced by alkylating stress in Mycobacterium smegmatis.
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Di Somma A, Caterino M, Soni V, Agarwal M, di Pasquale P, Zanetti S, Molicotti P, Cannas S, Nandicoori VK, and Duilio A
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- Acetyltransferases antagonists & inhibitors, Acetyltransferases genetics, Alkylation, Bacterial Proteins antagonists & inhibitors, Bacterial Proteins genetics, Gene Expression Profiling, Multienzyme Complexes antagonists & inhibitors, Multienzyme Complexes genetics, Mycobacterium smegmatis enzymology, Mycobacterium smegmatis genetics, Mycobacterium tuberculosis enzymology, Mycobacterium tuberculosis genetics, N-Acetylneuraminic Acid metabolism, Nucleotidyltransferases antagonists & inhibitors, Nucleotidyltransferases genetics, Nucleotidyltransferases metabolism, Acetyltransferases metabolism, Bacterial Proteins metabolism, Biofilms growth & development, Methyl Methanesulfonate pharmacology, Multienzyme Complexes metabolism, Mycobacterium smegmatis growth & development, Mycobacterium tuberculosis growth & development
- Abstract
Living organisms have developed specific defence mechanisms to counteract hostile environmental conditions. Alkylation stress response mechanisms also occur in Mycobacterium tuberculosis (MTB) the pathogen responsible for tuberculosis. The effect of alkylating agents on the cellular growth of MTB was investigated using methyl methanesulfonate (MMS) as methyl donor demonstrating that limited doses of alkylating agents might affect MTB cell viability. A global investigation of Mycobacterium smegmatis response to alkylating stress was then pursued by differential proteomics to identify the most affected cellular pathways. Quantitative analysis of proteomic profiles demonstrated that most of the proteins upregulated in the presence of alkylating agents are involved in biofilm formation and/or cell wall biosynthesis. Tailored experiments confirmed that under stress conditions M. smegmatis elicits physical defence mechanisms by increasing biofilm formation. Among the upregulated proteins, we identified the GlmU bifunctional enzyme as a possible factor involved in biofilm production. Experiments with both conditional deletion and overexpressing glmU mutants demonstrated that down regulation of GlmU decreased M. smegmatis capabilities to produce biofilm whereas overexpression of the enzyme increased biofilm formation. These results were supported by inhibition of GlmU acetyltransferase activity with two different inhibitors, suggesting the involvement of this enzyme in the M. smegmatis defence mechanisms., (Copyright © 2019 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
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- 2019
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4. Tuberculides and extrapulmonary TB: an atypical manifestation.
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Biondi G, Sotgiu G, Molicotti P, Montesu MA, Puggioni GM, and Satta R
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- Adult, Biopsy, Female, Humans, Italy, Lymph Nodes pathology, Lymphadenitis microbiology, Lymphadenitis pathology, Skin pathology, Tuberculin Test, Tuberculosis, Cutaneous microbiology, Tuberculosis, Cutaneous pathology, Lymph Nodes microbiology, Lymphadenitis diagnosis, Mycobacterium tuberculosis isolation & purification, Tuberculosis, Cutaneous diagnosis
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- 2019
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5. Design, synthesis and antitubercular activity of 4-alkoxy-triazoloquinolones able to inhibit the M. tuberculosis DNA gyrase.
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Carta A, Bua A, Corona P, Piras S, Briguglio I, Molicotti P, Zanetti S, Laurini E, Aulic S, Fermeglia M, and Pricl S
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- Animals, Antifungal Agents chemical synthesis, Antifungal Agents chemistry, Antitubercular Agents chemical synthesis, Antitubercular Agents chemistry, Chlorocebus aethiops, Dose-Response Relationship, Drug, Drug Design, Microbial Sensitivity Tests, Models, Molecular, Molecular Structure, Mycobacterium tuberculosis enzymology, Quinolones chemical synthesis, Quinolones chemistry, Saccharomyces cerevisiae drug effects, Structure-Activity Relationship, Topoisomerase II Inhibitors chemical synthesis, Topoisomerase II Inhibitors chemistry, Vero Cells, Antifungal Agents pharmacology, Antitubercular Agents pharmacology, DNA Gyrase metabolism, Mycobacterium tuberculosis drug effects, Quinolones pharmacology, Topoisomerase II Inhibitors pharmacology
- Abstract
A number of new F-triazolequinolones (FTQs) and alkoxy-triazolequinolones (ATQs) were designed, synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv. Five out of 21 compounds exhibited interesting minimum inhibitory concentration (MIC) values (6.6-57.9 μM), ATQs generally being more potent than FTQs. Two ATQs, 21a and 30a, were endowed with the best anti-Mtb potency (MIC = 6.9 and 6.6 μM, respectively), and were not cytotoxic in a Vero cell line. Tested for activity against M. tuberculosis DNA gyrase in a DNA supercoiling activity assay, 21a and 30a showed IC
50 values (27-28 μM) comparable to that of ciprofloxacin (10.6 μM). 21a was next selected for screening against several Mtb strains obtained from clinical isolates, including multi-drug-resistant (MDR) variants. Importantly, this compound was effective in all cases, with very promising MIC values (4 μM) in the case of some isoniazid/rifampicin-resistant Mtb strains. Finally, computer-based simulations revealed that the binding mode of 21a in the Mtb gyrase cleavage core complexed with DNA and the relevant network of intermolecular interactions are utterly similar to those described for ciprofloxacin, yielding a molecular rationale for the comparable anti-mycobacterial and DNA gyrase inhibition activity of this quinolone., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)- Published
- 2019
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6. Tuberculosis in Sardinia: An investigation into the relationship between natives and immigrants.
- Author
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Ruggeri M, Molicotti P, Cubeddu M, Cannas S, Bua A, and Zanetti S
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- Antitubercular Agents pharmacology, Epidemiologic Studies, Genotype, Genotyping Techniques, Humans, Italy epidemiology, Microbial Sensitivity Tests, Minisatellite Repeats, Molecular Epidemiology, Molecular Typing, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis genetics, Tuberculosis transmission, Disease Transmission, Infectious, Emigrants and Immigrants, Genetic Variation, Mycobacterium tuberculosis classification, Mycobacterium tuberculosis isolation & purification, Population Groups, Tuberculosis epidemiology
- Abstract
Objective/background: Tuberculosis (TB) has had a recrudescence in the last few decades in Italy as a result of many factors, among which migration from countries where TB is endemic is one of them. In Sardinia, a major island of Italy, there was no knowledge of the mechanisms of transmission of TB in the immigrant subpopulation and the impact it may have on the native subpopulation and on the community as a whole. Therefore, a molecular epidemiological study was carried out to get a clearer picture of the number and genetic features of Mycobacterium tuberculosis strains isolated from immigrants and from natives in Sardinia., Methods: Two groups of clinical isolates of M. tuberculosis, one collected from immigrants and the other one from Sardinians, were analyzed in this study. The genotyping was executed through the variable number tandem repeat-mycobacterial interspersed repetitive units technique and a first-line antimycobacterial drug-susceptibility test was also carried out., Results: Thirty-six clinical isolates from immigrants and 25 from Sardinians were analyzed. Variable number tandem repeat-mycobacterial interspersed repetitive units technique showed that all of them belonged to different strains and there was a quite high allelic diversity among them. Moreover, data collected allowed the finding of, with a good approximation, the phylogenetic relations among the strains isolated and the best-known phylogenetic groups., Conclusion: The study pointed out that since every strain is different, there was no TB transmission in any of the subpopulations and between immigrants and natives. This showed that the presence of immigrants was not a risk factor for contracting TB in the community., (Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2016
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7. Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries.
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Molicotti P, Bua A, and Zanetti S
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- Cost-Benefit Analysis, Developing Countries, Humans, Clinical Laboratory Techniques economics, Clinical Laboratory Techniques methods, Diagnostic Tests, Routine economics, Diagnostic Tests, Routine methods, Mycobacterium tuberculosis isolation & purification, Tuberculosis diagnosis
- Abstract
Tuberculosis remains one of the major causes of global death from a single infectious agent. This situation is worsened by the HIV/AIDS pandemic because one-third of HIV/AIDS patients are co-infected with Mycobacterium tuberculosis. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely manner, allowing continued M. tuberculosis transmission within communities. Diagnosis of tuberculosis can be made using indirect and direct methods. The indirect tests, such as interferon-gamma release assays, provide a new diagnostic method for M. tuberculosis infection, but do not discriminate between infection and active disease. The most common direct method for diagnosing TB worldwide is sputum smear microscopy (developed more than 100 years ago), where bacteria are observed in sputum samples examined under a microscope. In countries with more developed laboratory capacities, cases of tuberculosis may also be diagnosed using culture methods (the current gold standard) or, increasingly, using rapid molecular tests. In this review, we discuss the traditional methods for the diagnosis of tuberculosis. We also discuss other inexpensive assays that can be used to detect the presence of M. tuberculosis.
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- 2014
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8. In honor of Professor Giovanni Fadda: a fighter against tuberculosis.
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Zanetti S, Sechi LA, Molicotti P, Delogu G, and Rubino S
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- History, 20th Century, History, 21st Century, Humans, Molecular Typing methods, Mycobacterium tuberculosis classification, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis immunology, Tuberculosis epidemiology, Tuberculosis prevention & control, Tuberculosis Vaccines immunology, Virulence Factors genetics, Virulence Factors metabolism, Microbiology history, Mycobacterium tuberculosis pathogenicity, Tuberculosis microbiology
- Published
- 2013
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9. Performance of QuantiFERON TB in a student population at low risk of tuberculosis.
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Molicotti P, Bua A, and Zanetti S
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- Humans, Mycobacterium tuberculosis immunology, Tuberculosis prevention & control, Tuberculosis Vaccines therapeutic use, Vaccination methods
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- 2012
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10. Tuberculosis patients are characterized by a low-IFN-γ/high-TNF-α response to methylated HBHA produced in M. smegmatis.
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Molicotti P, Bua A, Cubeddu M, Cannas S, Delogu G, and Zanetti S
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- Bacterial Proteins genetics, Cells, Cultured, Humans, Membrane Proteins genetics, Mycobacterium smegmatis genetics, Recombinant Proteins genetics, Recombinant Proteins immunology, Bacterial Proteins immunology, Interferon-gamma metabolism, Leukocytes, Mononuclear immunology, Membrane Proteins immunology, Mycobacterium tuberculosis immunology, Tuberculosis immunology, Tumor Necrosis Factor-alpha metabolism
- Abstract
Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with heparin-binding hemagglutinin (HBHA). Tuberculosis (TB) patients showed an HBHA-specific T-cell response characterized by low-IFN-γ/high-TNF-α secretion, while asymptomatic subjects with latent infection (LTBI) and TB patients under therapy showed a pattern with high IFN-γ/low TNF-α. These results underscore the usefulness of HBHA in helping to distinguish LTBI subjects versus TB patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)
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- 2011
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11. Methylated HBHA produced in M. smegmatis discriminates between active and non-active tuberculosis disease among RD1-responders.
- Author
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Delogu G, Chiacchio T, Vanini V, Butera O, Cuzzi G, Bua A, Molicotti P, Zanetti S, Lauria FN, Grisetti S, Magnavita N, Fadda G, Girardi E, and Goletti D
- Subjects
- Adult, CD4-Positive T-Lymphocytes immunology, Demography, Female, Humans, Immunologic Memory, Interferon-gamma immunology, Lectins immunology, Male, Methylation, Middle Aged, ROC Curve, Reagent Kits, Diagnostic, Recombinant Proteins immunology, Time Factors, Antigens, Bacterial immunology, Lectins biosynthesis, Mycobacterium smegmatis metabolism, Mycobacterium tuberculosis immunology, Tuberculosis diagnosis, Tuberculosis immunology
- Abstract
Background: A challenge in tuberculosis (TB) research is to develop a new immunological test that can help distinguish, among subjects responsive to QuantiFERON TB Gold In tube (QFT-IT), those who are able to control Mtb replication (remote LTBI, recent infection and past TB) from those who cannot (active TB disease). IFN-γ response to the Heparin-binding-hemagglutinin (HBHA) of Mtb has been associated with LTBI, but the cumbersome procedures of purifying the methylated and immunological active form of the protein from Mtb or M. bovis Bacillus Calmette et Guerin (BCG) have prevented its implementation in a diagnostic test. Therefore, the aim of the present study was to evaluate the IFN-γ response to methylated HBHA of Mtb produced in M. smegmatis (rHBHAms) in individuals at different stages of TB who scored positive to QFT-IT., Methodology/principal Findings: 87 individuals at different stages of TB who scored positive to QFT-IT were selected. IFN-γ response to in vitro whole blood stimulation with rHBHAms was evaluated by short-term and long-term tests and detected by ELISA or flow cytometry. We demonstrated that the IFN-γ response to rHBHAms is mediated by CD4(+) T-cells with an effector-memory phenotype. This response, evaluated by short-term-tests, is significantly lower in active TB than in remote LTBI (p = 0.0010) and past TB (p = 0.0152). These results were confirmed by long-term tests. The qualitative data confirmed that IFN-γ responses higher than the cut-off point identified by ROC analysis are associated with the status of non-active disease., Conclusions: In this study we show that the T-cell response to a recombinant and methylated HBHA of Mtb produced in M. smegmatis is useful to discriminate between active and non-active TB disease among those responsive to QFT-IT in a whole blood system. Further studies are needed to improve the accuracy of the assay.
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- 2011
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12. Molecular characterization of Sardinian Mycobacterium tuberculosis isolates by IS6110 restriction fragment length polymorphism, MIRU-VNTR and rep-PCR.
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Masala S, Molicotti P, Bua A, Zumbo A, Delogu G, Sechi LA, and Zanetti S
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- Humans, Italy epidemiology, Molecular Epidemiology, Polymorphism, Restriction Fragment Length, Bacterial Typing Techniques methods, DNA Transposable Elements genetics, Minisatellite Repeats genetics, Mycobacterium tuberculosis classification, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, Polymerase Chain Reaction methods, Tuberculosis diagnosis, Tuberculosis epidemiology, Tuberculosis microbiology
- Abstract
An evaluation of the utility of rep PCR typing compared to the 15 loci discriminatory set of MIRU-VNTR was undertaken. Twenty-nine isolates of Mycobacterium tuberculosis from patients were examined. Genomic DNA was extracted from the isolates by standard method. The number of copies of tandem repeats of the 15 MIRU-VNTR loci was determined by PCR amplification and agarose gel electrophoresis of the amplicons. M. tuberculosis outbreak-related strains were distinguished from other isolates. MIRU-VNTR typing identified 4 major clusters of strains. The same isolates clustered together after RFLP typing, but rep-PCR identified only 3 of them. The concordance between RFLP and MIRU-VNTR typing was complete, with the exception of two isolates with identical RFLP patterns that differed in the number of tandem repeat copies at two MIRU-VNTR alleles. A further isolate, even sharing the same RFLP pattern, differed by one repeat from the rest of its cluster. We also tested the use of an automated rep-PCR for clinical laboratory applications but it failed to identify the link between two pairs of epidemiologically related strains clustered by the other 2 techniques. For superior discrimination, ease of comparison of results and lower cost, MIRU-VNTR typing should be the favored PCR-based typing tool.
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- 2010
13. Usefulness of the QuantiFERON-TB-Gold in tube in a population at risk of bovine tubercular infection.
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Bua A, Molicotti P, Cannas S, Cubeddu M, Ruggeri M, Contena S, Delogu R, and Zanetti S
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- Adult, Aged, Agricultural Workers' Diseases immunology, Agricultural Workers' Diseases microbiology, Animals, Cattle, Female, Humans, Male, Middle Aged, Mycobacterium tuberculosis immunology, Reagent Kits, Diagnostic, Risk Factors, Tuberculosis immunology, Tuberculosis microbiology, Young Adult, Agricultural Workers' Diseases diagnosis, Immunologic Tests methods, Mycobacterium tuberculosis isolation & purification, Tuberculosis diagnosis, Tuberculosis, Bovine microbiology
- Abstract
The effectiveness of the QuantiFERON-TB-Gold in tube was compared with PPD to detect tuberculosis infection in the staff of cattle-farms, as a consequence of an outbreak of bovine tuberculosis in livestock. The data revealed the advantage of the immunological test for the specific detection of subjects infected by Mycobacterium tuberculosis complex.
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- 2009
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14. Phages specific for mycobacterial lipoarabinomannan help serodiagnosis of tuberculosis.
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Bua A, Rosu V, Molicotti P, Das Gupta SK, Ahmed N, Zanetti S, and Sechi LA
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- Antibodies, Bacterial blood, Antibodies, Bacterial immunology, Antigens, Bacterial biosynthesis, Antigens, Bacterial immunology, Bacteriophages metabolism, Epitopes biosynthesis, Epitopes immunology, Humans, Lipopolysaccharides biosynthesis, Peptide Library, Serologic Tests methods, Tuberculosis, Pulmonary immunology, Tuberculosis, Pulmonary metabolism, Bacteriophages immunology, Lipopolysaccharides immunology, Mycobacterium tuberculosis immunology, Tuberculosis, Pulmonary diagnosis
- Abstract
This study evaluated the possibility to use six phages specific to the Mycobacterium tuberculosis lipoarabinomannan (LAM) as tools for tubercular serodiagnosis. We analysed sera samples from 30 subjects with active tuberculosis (TB+), 30 with latent tubercular infection (LTBI) and 60 healthy subjects as controls (K). Our data indicated a good antibody response of the TB+ and LTBI patients against the phage Ri(7)17; the optical density (OD) values obtained from sera patients was statistically significant when compared to the control samples. Our results confirm that phage display technology might be useful to develop new tools for diagnosis of tuberculosis.
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- 2009
15. Performance of QuantiFERON-TB testing in a tuberculosis outbreak at a primary school.
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Molicotti P, Bua A, Mela G, Olmeo P, Delogu R, Ortu S, Sechi LA, and Zanetti S
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- Antigens, Bacterial analysis, Child, Female, Humans, Lung diagnostic imaging, Male, Mycobacterium tuberculosis immunology, Radiography, Sensitivity and Specificity, T-Lymphocytes chemistry, T-Lymphocytes immunology, Tuberculosis, Pulmonary epidemiology, Disease Outbreaks, Immunoassay, Interferon-gamma analysis, Mycobacterium tuberculosis isolation & purification, Tuberculin Test, Tuberculosis, Pulmonary diagnosis
- Abstract
This study compared the effectiveness of the QuantiFERON-TB Gold (QFT) assay with the Mantoux tuberculin skin test to detect Mycobacterium tuberculosis infection in 29 children during a school outbreak of tuberculosis. Of the 21 children with M. tuberculosis infection, 11 had a radiograph suggestive of the infection. The QFT assay was positive in all 21 of the children, and the Mantoux test was negative at first testing in 2 children (1 of whom was the sentinel case). The findings demonstrate that the QFT test is extremely useful in accurately identifying infected and uninfected children, permitting rapid intervention.
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- 2008
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16. [1,2,3]Triazolo[4,5-h]quinolones. A new class of potent antitubercular agents against multidrug resistant Mycobacterium tuberculosis strains.
- Author
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Carta A, Palomba M, Paglietti G, Molicotti P, Paglietti B, Cannas S, and Zanetti S
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- Anti-Bacterial Agents pharmacology, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Drug Design, Humans, Inhibitory Concentration 50, Microbial Sensitivity Tests, Models, Chemical, Anti-Bacterial Agents chemistry, Chemistry, Pharmaceutical methods, Drug Resistance, Bacterial, Drug Resistance, Multiple, Mycobacterium tuberculosis metabolism, Quinolones chemistry, Triazoles chemistry, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
In this preliminary study we report the activity of 3-methyl-9-substituted-6-oxo-6,9-dihydro-3H-[1,2,3]-triazolo[4,5-h]quinolone-carboxylic acids and their esters as a new class of antiinfective agents against MDR Mycobacterium tuberculosis. In antitubercular screening against H37Rv and 11 clinically isolated strains of M. tuberculosis several derivatives (1o,3a,c,i,j,p) showed MIC(90) in the range 0.5-3.2 microg/mL. 3c showed no cytotoxicity and proved to be the most potent derivative exhibiting MIC(90)=0.5 microg/mL against all M. tuberculosis strains and infected human macrophages (J774-A1) tested.
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- 2007
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17. In vitro efficacy of Linezolid on clinical strains of Mycobacterium tuberculosis and other mycobacteria.
- Author
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Molicotti P, Ortu S, Bua A, Cannas S, Sechi LA, and Zanetti S
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- Drug Resistance, Bacterial, Humans, Italy, Linezolid, Microbial Sensitivity Tests methods, Mycobacterium classification, Mycobacterium isolation & purification, Mycobacterium tuberculosis isolation & purification, Acetamides pharmacology, Anti-Infective Agents pharmacology, Mycobacterium drug effects, Mycobacterium tuberculosis drug effects, Oxazolidinones pharmacology
- Abstract
Linezolid, an oxazolidinone that acts by inhibiting protein synthesis, was evaluated in strains of tuberculosis and non-tubercular mycobacteria resistant to one or more drugs isolated in northern Sardinia. The in vitro activity of Linezolid (Pfizer) was assessed on different isolates of Mycobacterium spp. from clinical samples by the Proportional Method. Linezolid demonstrated an excellent activity against the 24 strains of M. tuberculosis and against M. gordonae, M. marinum, M. aurum, M. phlei, and M. avium, with MIC values ranging from 0.5 to 2 microg/ml. Linezolid can be used in combination with the standard antitubercular medications, or as an effective therapeutic alternative in infections caused by M. tuberculosis or by other species of non-tubercular mycobacteria.
- Published
- 2006
18. Antimycobacterial agents. Novel diarylpyrrole derivatives of BM212 endowed with high activity toward Mycobacterium tuberculosis and low cytotoxicity.
- Author
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Biava M, Porretta GC, Poce G, Supino S, Deidda D, Pompei R, Molicotti P, Manetti F, and Botta M
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- Animals, Antitubercular Agents pharmacology, Antitubercular Agents toxicity, Chlorocebus aethiops, Microbial Sensitivity Tests, Models, Molecular, Morpholines pharmacology, Morpholines toxicity, Piperazines pharmacology, Piperazines toxicity, Pyrroles pharmacology, Pyrroles toxicity, Quantitative Structure-Activity Relationship, Vero Cells, Antitubercular Agents chemical synthesis, Morpholines chemical synthesis, Mycobacterium tuberculosis drug effects, Piperazines chemical synthesis, Pyrroles chemical synthesis
- Abstract
On the basis of suggestions derived either from a pharmacophoric model for antitubercular agents or from a structure-activity relationship analysis of many pyrroles previously described by us, we report here the design and synthesis of new analogues of 1,5-(4-chlorophenyl)-2-methyl-3-(4-methylpiperazin-1-yl)methyl-1H-pyrrole (BM212). Various substituents with different substitution patterns were added to both positions 1 and 5 of the pyrrole nucleus to evaluate their influence on the activity toward Mycobacterium tuberculosis (MTB) and atypical mycobacteria. Biological data showed that, although some nontuberculosis mycobacterial strains were found to be sensitive, MIC values were higher than those found toward MTB. The best compound (1-(4-fluorophenyl)-2-methyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole, 5) possessed a MIC of 0.4 microg/mL (better than BM212 and streptomycin) and a very high protection index (160), better than BM212, isoniazid, and streptomycin (6, 128, and 128, respectively). Finally, molecular modeling studies were performed to rationalize the activity of the new compounds in terms of both superposition onto a pharmacophoric model for antitubercular compounds and their hydrophobic character.
- Published
- 2006
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19. Rapid detection and identification of Mycobacterium tuberculosis by Real Time PCR and Bactec 960 MIGT.
- Author
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Ortu S, Molicotti P, Sechi LA, Pirina P, Saba F, Vertuccio C, Deriu A, Maida I, Mura MS, and Zanetti S
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- DNA Transposable Elements genetics, DNA, Bacterial chemistry, DNA, Bacterial genetics, Humans, Mycobacterium tuberculosis genetics, Sensitivity and Specificity, Taq Polymerase chemistry, Mycobacterium tuberculosis isolation & purification, Polymerase Chain Reaction methods, Tuberculosis microbiology
- Abstract
We have developed a Real-Time PCR assay to detect M. tuberculosis using the iCycler iQ detection system by TaqMan assay directly on the clinical specimen. A total of 513 clinical samples were taken from patients with suspected tuberculosis and other patients that had an active mycobacterial infection, as well as patients with diagnosed tuberculosis who were receiving antitubercular therapy. The sensitivity and specificity of this assay, 10% and 100%, respectively, were compared to those of conventional microbiological methods.
- Published
- 2006
20. Drug resistance and the genotypic characteristics of rpoB and katG in rifampicin- and/or isoniazid-resistant Mycobacterium tuberculosis isolates in central Vietnam.
- Author
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Thi Binh Nguyen Nguyen, Thi Kieu Diem Nguyen, Van Hue Truong, Thi Tuyet Ngoc Tran, van Bao Thang Phan, Thi Tuyen Nguyen, Hoang Bach Nguyen, Viet Quynh Tram Ngo, Van Tuan Mai, and Molicotti, Paola
- Subjects
TUBERCULOSIS microbiology ,ANTIBIOTICS ,GENETIC mutation ,STRATEGIC planning ,MOLECULAR diagnosis ,CONFIDENCE intervals ,DRUG resistance ,ISONIAZID ,MYCOBACTERIUM tuberculosis ,GENOTYPES ,RESEARCH funding ,DESCRIPTIVE statistics ,RIFAMPIN ,DRUG resistance in microorganisms ,POLYMERASE chain reaction - Abstract
Objectives: Tuberculosis (TB) and drug-resistant TB (DR-TB) are national health burdens in Vietnam. In this study, we investigated the prevalence of rifampicin (RIF) and/or isoniazid (isonicotinic acid hydrazide, INH) resistance in patients with suspected TB, and applied appropriate techniques to help rapidly target DR-TB. Methods: In total, 1,547 clinical specimens were collected and cultured using the BACTEC MGIT system (Becton Dickinson and Co.). A resazurin microtiter assay (REMA) was used to determine the proportions of RIF and/or INH resistance. A real-time polymerase chain reaction panel with TaqMan probes was employed to identify the mutations of rpoB and katG associated with DR-TB in clinical isolates. Genotyping of the identified mutations was also performed. Results: A total of 468 Mycobacterium tuberculosis isolates were identified using the REMA. Of these isolates, 106 (22.6%) were found to be resistant to 1 or both antibiotics. Of the resistant isolates, 74 isolates (69.8%) were resistant to isoniazid (INH) only, while 1 isolate (0.94%) was resistant to RIF only. Notably, 31 isolates (29.24%) were resistant to both antibiotics. Of the 41 phenotypically INH-resistant isolates, 19 (46.3%) had the Ser315Thr mutation. There were 8 different rpoB mutations in 22 (68.8%) of the RIF-resistant isolates. The most frequently detected mutations were at codons 531 (37.5%), 526 (18.8%), and 516 (6.3%). Conclusion: To help prevent new cases of DR-TB in Vietnam, it is crucial to gain a comprehensive understanding of the genotypic DR-TB isolates. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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21. Could inducible protein-10 and heparin-binding hemagglutinin improve the detection of Mycobacterium tuberculosis-infected subjects in a country with low incidence of tuberculosis?
- Author
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Molicotti, Paola, Bua, Alessandra, Cubeddu, Marina, Ruggeri, Melania, Mura, Maria Stella, Pirina, Pietro, and Zanetti, Stefania
- Subjects
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MYCOBACTERIUM tuberculosis , *HEPARIN , *CARRIER proteins , *HEMAGGLUTININ , *DISEASE incidence , *BIOMARKERS , *INTERFERON gamma release tests , *DIAGNOSIS , *DIAGNOSTIC errors , *TUBERCULIN test , *TUBERCULOSIS , *CONTACT tracing , *ODDS ratio - Abstract
Background: This study aimed to evaluate inducible protein-10 (IP-10) as a biomarker besides interferon-gamma (IFN-?) to improve the identification of active tuberculosis (TB) and latent tubercular infection (LTBI) in a country with a low incidence of TB. Methods: Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with region-of-difference-1 (RD1)-specific peptides and with heparin-binding hemagglutinin (HBHA) to determine the release of IP-10 and IFN-?. Results: No statistically significant difference was observed between positive rates of IP-10 and IFN-? after RD1-specific peptide stimulation in the TB and LTBI groups; a different response was detected in QuantiFERON TB-gold test-negative (QFT-) subjects. A significantly different proportion of positive responses was observed between IP-10 and IFN-? following HBHA stimulation in the TB group and in the QFT- group but not in the LTBI group. Conclusions: The IP-10 test seemed to identify false-negative QFT results in some subjects with a positive IFN-?/IP-10/HBHA pattern. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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22. Epidemic of tuberculosis in a high school in Northern Sardinia
- Author
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Bua, Alessandra, Molicotti, Paola, Zanetti, Anna, Ruggeri, Melania, Cubeddu, Marina, Cannas, Sara, Peana, Nanni, Sali, Michela, Delogu, Giovanni, and Zanetti, Stefania
- Subjects
TUBERCULOSIS ,EPIDEMICS ,HEALTH of high school students ,CHEST X rays ,MYCOBACTERIUM tuberculosis - Abstract
Abstract: The aim of this study was to investigate the Mycobacterium tuberculosis transmission among high school student and teacher populations in a high school in Northern Sardinia. Tuberculin skin-test screening, chest-X-rays, QuantiFERON-TB Gold, microbiological examination, spoligotyping and variable numbers of tandem repeats (VNTR) analysis of M. tuberculosis isolates were performed. This study indicates the effectiveness of the epidemiological investigation. [Copyright &y& Elsevier]
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- 2012
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23. Antitubercular activity of quinolizidinyl/pyrrolizidinylalkyliminophenazines.
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Tonelli, Michele, Novelli, Federica, Tasso, Bruno, Sparatore, Anna, Boido, Vito, Sparatore, Fabio, Cannas, Sara, Molicotti, Paola, Zanetti, Stefania, Parapini, Silvia, and Loddo, Roberta
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ANTITUBERCULAR agents , *CLOFAZIMINE , *MYCOBACTERIUM tuberculosis , *CELL-mediated cytotoxicity , *NUCLEAR magnetic resonance spectroscopy , *COLUMN chromatography - Abstract
Novel riminophenazine derivatives, characterized by the presence of the basic and cumbersome quinolizidinylalkyl and pyrrolizidinylethyl moieties, have been synthesized and tested (Rema test) against Mycobacterium tuberculosis H 37 R v and H 37 R a , and six clinical isolates of Mycobacterium avium and Mycobacterium tuberculosis. Most compounds exhibited potent activity against the tested strains, resulting more active than clofazimine, isoniazid and ethambutol. The best compounds ( 4 , 5 , 12 and 13 ) exhibited a MIC in the range 0.82–0.86 μM against all strains of Mycobacterium tuberculosis and, with the exception of 4 a MIC around 3.3 μM versus M. avium . The corresponding values for clofazimine (CFM) were 1.06 and 4.23 μM, respectively. Cytotoxicity was evaluated against three cell lines and compound 4 displayed a selectivity index (SI) versus the human cell line MT-4 comparable with that of CFM (SI = 5.23 vs 6.4). Toxicity against mammalian Vero 76 cell line was quite lower with SI = 79. [ABSTRACT FROM AUTHOR]
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- 2014
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24. Synthesis and anti-mycobacterial activities of triazoloquinolones
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Carta, Antonio, Palomba, Michele, Briguglio, Irene, Corona, Paola, Piras, Sandra, Jabes, Daniela, Guglierame, Paola, Molicotti, Paola, and Zanetti, Stefania
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QUINOLONE antibacterial agents , *MYCOBACTERIUM tuberculosis , *ISONIAZID , *RIFAMPIN , *FLUOROQUINOLONES , *RING formation (Chemistry) , *MULTIDRUG resistance , *METHYL groups - Abstract
Abstract: A number of quinolone derivatives have been reported to possess anti-mycobacterial activity. Generally. Mycobacterium tuberculosis isolates expressing resistance to both isoniazid and rifampin are susceptible to fluoroquinolones. Benzotriazole is a hetero-bicyclic aromatic ring endowed with interesting chemical and biological properties and pharmacological activities. In a preliminary study we have recently reported the activity of triazolo[4,5-h]quinolone-carboxylic acids, a new class of benzotriazole derivatives active against multi-drug resistant M. tuberculosis (MDR-Mtb). In this study we confirm that this novel class of quinolones is endowed with a selective anti-mycobacterial activity, coupled with absence of cytotoxicity. The SAR analysis of the new derivatives in comparison with the previous series shows that the methyl group is the most effective substituent in both N-3 and N-9 positions of the ring system. [Copyright &y& Elsevier]
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- 2011
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25. Design, synthesis and antitubercular activity of 4-alkoxy-triazoloquinolones able to inhibit the M. tuberculosis DNA gyrase
- Author
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Erik Laurini, Antonio Carta, Sabrina Pricl, Paola Corona, Irene Briguglio, Alessandra Bua, Paola Molicotti, Suzana Aulic, Maurizio Fermeglia, Sandra Piras, Stefania Anna Lucia Zanetti, Carta, Antonio, Bua, Alessandra, Corona, Paola, Piras, Sandra, Briguglio, Irene, Molicotti, Paola, Zanetti, Stefania, Laurini, Erik, Aulic, Suzana, Fermeglia, Maurizio, and Pricl, Sabrina
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Models, Molecular ,Antifungal Agents ,medicine.drug_class ,Antitubercular Agents ,Microbial Sensitivity Tests ,Saccharomyces cerevisiae ,Quinolones ,In vitro and in silico studies ,01 natural sciences ,DNA gyrase ,03 medical and health sciences ,Minimum inhibitory concentration ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Chlorocebus aethiops ,medicine ,Animals ,Topoisomerase II Inhibitors ,Vero Cells ,030304 developmental biology ,Pharmacology ,0303 health sciences ,M. tuberculosis DNA gyrase ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Isoniazid ,M. tuberculosis clinical strain ,General Medicine ,Mycobacterium tuberculosis ,Quinolone ,Triazoloquinolone ,0104 chemical sciences ,Ciprofloxacin ,Biochemistry ,DNA Gyrase ,Drug Design ,Triazoloquinolones ,Vero cell ,DNA supercoil ,Antitubercular activity ,M. tuberculosis clinical strains ,DNA ,medicine.drug - Abstract
A number of new F-triazolequinolones (FTQs) and alkoxy-triazolequinolones (ATQs) were designed, synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv. Five out of 21 compounds exhibited interesting minimum inhibitory concentration (MIC) values (6.6-57.9 microM), ATQs generally being more potent than FTQs. Two ATQs, 21a and 30a, were endowed with the best anti-Mtb potency (MIC = 6.9 and 6.6 microM, respectively), and were not cytotoxic in a Vero cell line. Tested for activity against M. tuberculosis DNA gyrase in a DNA supercoiling activity assay, 21a and 30a showed IC50 values (27-28 microM) comparable to that of ciprofloxacin (10.6 microM). 21a was next selected for screening against several Mtb strains obtained from clinical isolates, including multi-drug-resistant (MDR) variants. Importantly, this compound was effective in all cases, with very promising MIC values (4 microM) in the case of some isoniazid/rifampicin-resistant Mtb strains. Finally, computer-based simulations revealed that the binding mode of 21a in the Mtb gyrase cleavage core complexed with DNA and the relevant network of intermolecular interactions are utterly similar to those described for ciprofloxacin, yielding a molecular rationale for the comparable anti-mycobacterial and DNA gyrase inhibition activity of this quinolone.
- Published
- 2019
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