Paolo Miotto
A5088302359- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Diagnosis and treatment of tuberculosis
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Pneumonia and Respiratory Infections
- Cancer therapeutics and mechanisms
- Bacteriophages and microbial interactions
- Infectious Diseases and Tuberculosis
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA modifications and cancer
- MicroRNA in disease regulation
- Biosensors and Analytical Detection
- Genomics and Phylogenetic Studies
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- HIV/AIDS drug development and treatment
- Infectious Diseases and Mycology
- Advanced Biosensing Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Antibiotic Use and Resistance
- COVID-19 diagnosis using AI
- Advanced biosensing and bioanalysis techniques
- Cell Image Analysis Techniques
Vita-Salute San Raffaele University
2016-2025
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2025
IRCCS Ospedale San Raffaele
2007-2022
San Raffaele University of Rome
2006-2018
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
2006
A clear understanding of the genetic basis antibiotic resistance in Mycobacterium tuberculosis is required to accelerate development rapid drug susceptibility testing methods based on sequence. Raw genotype–phenotype correlation data were extracted as part a comprehensive systematic review develop standardised analytical approach for interpreting associated mutations rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin,...
ABSTRACT Antibiotic-resistant tuberculosis poses a global threat, causing the deaths of hundreds thousands people annually. While whole-genome sequencing (WGS), with its unprecedented level detail, promises to play an increasingly important role in diagnosis, data analysis is daunting challenge. Here, we present simple-to-use web service (free for academic use at http://phyresse.org ). Delineating both lineage and resistance, it provides state-of-the-art methodology life scientists...
Molecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for
The Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) presents here a data compendium of 12,289 Mycobacterium tuberculosis global clinical isolates, all which have undergone whole-genome sequencing and had their minimum inhibitory concentrations to 13 antitubercular drugs measured in single assay. It is the largest matched phenotypic genotypic dataset M. date. Here, we provide summary detailing breadth collected, along with description how isolates...
The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in binary manner (classifying strains as either susceptible or resistant). Here, we used multivariable linear mixed model alongside whole genome sequencing quantitative microtiter plate assay relate genomic mutations minimum inhibitory concentration (MIC) 15,211...
In many countries, regular monitoring of the emergence resistance to anti-tuberculosis drugs is hampered by limitations phenotypic testing for drug susceptibility. We therefore evaluated use genetic sequencing surveillance in tuberculosis.Population-level surveys were done hospitals and clinics seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, Ukraine) evaluate estimate Mycobacterium tuberculosis isolates rifampicin, isoniazid, ofloxacin, moxifloxacin,...
Pyrazinamide (PZA) is a prodrug that converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations offers potential for rapid detection pyrazinamide resistance (PZA(r)). However, genetic variants are highly variable and scattered over full length pncA, complicating development molecular test. We performed large multicenter study assessing sequence variations 1,950 clinical isolates, including 1,142...
Resistance to fluoroquinolones (FLQ) and second-line injectable drugs (SLID) is steadily increasing, especially in eastern European countries, posing a serious threat effective tuberculosis (TB) infection control adequate patient management. The availability of rapid molecular tests for the detection extensively drug-resistant TB (XDR-TB) critical areas with high rates multidrug-resistant (MDR-TB) XDR-TB limited conventional drug susceptibility testing (DST) capacity. We conducted...
ABSTRACT Low-level rifampin resistance associated with specific rpoB mutations (referred as “disputed”) in Mycobacterium tuberculosis is easily missed by some phenotypic methods. To understand the mechanism which are systematically MGIT testing, we performed an silico analysis of their effect on structural interaction between RpoB protein and rifampin. We also characterized 24 representative clinical isolates determining MICs 7H10 agar testing them extended protocol. analyzed 2,097 line...
Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) clinical data. We developed unified analysis pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) identify variants assign lineage MTBC sequence Stringent thresholds quality control measures...
Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, understanding resistance mechanisms poor, which hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine determinants, we combined experimental evolution, protein modelling, genome sequencing, phenotypic data.
There were approximately 10 million tuberculosis (TB) cases in 2020, of which 500,000 drug-resistant. Only one third drug-resistant TB diagnosed and enrolled on appropriate treatment, an issue partly driven by a lack rapid, accurate drug-susceptibility testing (DST) tools deployable peripheral settings. In 2014, World Health Organization (WHO) published target product profiles (TPPs) detailed minimal optimal criteria to address high-priority diagnostic needs, including DST. Since then, the...
ABSTRACT Mycobacterium tuberculosis is one of the leading causes death worldwide, and multidrug-resistant (MDR-TB) associated with a high case fatality rate. Rapid identification resistant strains crucial for early administration appropriate therapy, prevention development further resistance, to curtail spread MDR strains. The Genotype MTBDR (Hain Lifescience, Nehren, Germany) reverse hybridization line probe assay designed rapid detection rpoB katG gene mutations in clinical isolates....
Only few small RNAs (sRNAs) have been characterized in Mycobacterium tuberculosis and their role regulatory networks is still poorly understood. Here we report a genome-wide characterization of sRNAs M. integrating experimental computational analyses. Global RNA-seq analysis exponentially growing cultures H37Rv had previously identified 1373 sRNA species. In the present show that 258 (19%) these were also by microarray expression. This set included 22 intergenic sRNAs, 84 mapping within...
Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify serum miRNA signature be used the diagnosis tuberculosis (TB). To account variations due genetic makeup, we enrolled adults from two study settings Europe Africa. The following categories subjects were considered: healthy (H), active pulmonary TB (PTB), TB, HIV...
Continued progress in addressing challenges associated with detection and management of tuberculosis requires new diagnostic tools. These tools must be able to provide rapid accurate information for detecting resistance guide selection the treatment regimen each patient. To achieve this goal, globally representative genotypic, phenotypic, clinical data are needed a standardized curated platform. A global partnership academic institutions, public health agencies, nongovernmental organizations...
Antibiotic resistance among bacterial pathogens poses a major global health threat. Mycobacterium tuberculosis complex (MTBC) is estimated to have the highest rates of any pathogen globally. Given low growth rate and need for biosafety level 3 laboratory, only realistic avenue scale up drug susceptibility testing (DST) this rely on genotypic techniques.
Tight control of inflammatory gene expression by antagonistic environmental cues is key to ensure immune protection while preventing tissue damage. Prostaglandin E2 (PGE2) modulates macrophage activation during homeostasis and disease, but the underlying mechanisms remain incompletely characterized. Here we dissected genomic properties lipopolysaccharide (LPS)-induced genes whose antagonized PGE2. The latter molecule targeted a set enhancers that, already in unstimulated macrophages,...
We sought to identify resistance patterns and key drivers of recent multidrug-resistant tuberculosis (MDR-TB) transmission in a TB-prevalent area Peru. Cross-sectional study including MDR Mycobacterium complex (Mtbc) strains identified Callao-Peru between April 2017 February 2019. Mtbc DNA was extracted for whole genome sequencing which used phylogenetic inference, clustering, mutation analyses. Clusters indicative were defined based on strain-to-strain distance ≤5 (D5) single nucleotide...
ABSTRACT Transcriptional responses in bacteria following antibiotic exposure offer insights into mechanism of action, bacterial responses, and characterization antimicrobial resistance. We aimed to define the transcriptional response (TAR) Mycobacterium tuberculosis (Mtb) isolates for clinically relevant drugs by pooling analyzing Mtb microarray RNA-seq data sets. generated 99 transcription profiles across 17 antibiotics, with 76% using 3–24 hours 49% within one doubling WHO critical...