Publications by authors named "Charlotte Avanzi"

We found Mycobacterium leprae, the most common etiologic agent of Hansen disease or leprosy, in tissues from 9 (18.75%) of 48 nine-banded armadillos (Dasypus novemcinctus) collected across continental Ecuador. Finding evidence of a wildlife reservoir is the first step to recognizing leprosy zoonotic transmission pathway in Ecuador or elsewhere.

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The new world was considered free of leprosy before the arrival of Europeans. In Suriname, historical migration routes suggest that leprosy could have been introduced from West Africa by the slave trade, from Asia by indentured workers, from Europe by the colonizers, and more recently by Brazilian gold miners. Previous molecular studies on environmental and ancient samples suggested a high variability of the strains circulating in the country, possibly resulting from the various migration waves.

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Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease's evolutionary history, the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England.

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This study investigates the efficacy of proteomic analysis of human remains to identify active infections in the past through the detection of pathogens and the host response to infection. We advance leprosy as a case study due to the sequestering of sufferers in leprosaria and the suggestive skeletal lesions that can result from the disease. Here we present a sequential enzyme extraction protocol, using trypsin followed by ProAlanase, to reduce the abundance of collagen peptides and in so doing increase the detection of non-collagenous proteins.

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Accelerated SuFEx Click Chemistry (ASCC) is a powerful method for coupling aryl and alkyl alcohols with SuFEx-compatible functional groups. With its hallmark favorable kinetics and exceptional product yields, ASCC streamlines the synthetic workflow, simplifies the purification process, and is ideally suited for discovering functional molecules. We showcase the versatility and practicality of the ASCC reaction as a tool for the late-stage derivatization of bioactive molecules and in the array synthesis of sulfonate-linked, high-potency, microtubule targeting agents (MTAs) that exhibit nanomolar anticancer activity against multidrug-resistant cancer cell lines.

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Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, . To begin unraveling the molecular mechanisms of pathogenicity of , we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection.

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Introduction: Leprosy, an infectious disease caused by , remains a public health concern in endemic countries, particularly in Brazil. In this study, we conducted an active surveillance campaign in the hyperendemic city of Castanhal in the northeastern part of the state of Pará using clinical signs and symptoms combined with serological and molecular tools to diagnose new cases and to identify drug resistance of circulating strains and their distribution in the community.

Methods: During an active surveillance of one week, we enrolled 318 individuals using three different strategies to enroll subjects for this study: (i) an active survey of previously treated cases from 2006 to 2016 found in the Brazil National Notifiable Disease Information System database ( = 23) and their healthy household contacts (HHC) ( = 57); (ii) an active survey of school children (SC) from two primary public schools in low-income neighborhoods ( = 178), followed by visits to the houses of these newly diagnosed SC ( = 7) to examine their HHC ( = 34) where we diagnosed additional new cases ( = 6); (iii) and those people who spontaneously presented themselves to our team or the local health center with clinical signs and/or symptoms of leprosy ( = 6) with subsequent follow-up of their HHC when the case was confirmed ( = 20) where we diagnosed two additional cases ( = 2).

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Article Synopsis
  • The covalent modification of bacterial polysaccharides may influence their production, export, and biological functions, but it's unclear how mycobacteria, like Mycobacterium tuberculosis (Mtb), utilize similar mechanisms.
  • Research shows that specific succinyl groups on Mtb's lipoarabinomannan play a key role in determining the mannose-capping of this molecule, affecting its overall biological activity.
  • The absence of succinyl groups on Mtb's primary cell envelope polysaccharides results in heightened pro-inflammatory responses in both murine and human macrophages, highlighting succinylation as a vital factor in Mtb's regulation of inflammation.
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Bacteria from the genus include pathogens that cause serious diseases in humans and remain as difficult infectious agents to treat. Central to these challenges are the composition and organization of the mycobacterial cell envelope, which includes unique and complex glycans. Inositol is an essential metabolite for mycobacteria due to its presence in the structural core of the immunomodulatory cell envelope glycolipids phosphatidylinositol mannoside (PIM) and PIM-anchored lipomannan (LM) and lipoarabinomannan (LAM).

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Coupled with its rarity in non-endemic areas, the clinical heterogeneity of leprosy makes diagnosis very challenging. We report a diagnosis of multibacillary leprosy in a 22-year-old Indian woman, adopted at the age of 10 and living in Italy. The patient presented with painful skin lesions on the face, trunk, and lower and upper extremities, associated with dysesthesia and a motor deficit in her left leg following corticosteroid therapy interruption.

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We examined armadillos from museum collections in the United States using molecular assays to detect leprosy-causing bacilli. We found Mycobacterium leprae bacilli in samples from the United States, Bolivia, and Paraguay; prevalence was 14.8% in nine-banded armadillos.

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Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against .

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Biofilm growth is thought to be a significant obstacle to the successful treatment of infections. A search for agents capable of inhibiting biofilms led to our interest in 2-aminoimidazoles and related scaffolds, which have proven to display antibiofilm properties against a number of Gram-negative and Gram-positive bacteria, including and . The screening of a library of 30 compounds led to the identification of a compound, AB-2-29, which inhibits the formation of biofilms with an IC (the concentration required to inhibit 50% of biofilm formation) in the range of 12.

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Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and are implicated in the zoonotic transmission of leprosy in the United States. In Mexico, the existence of such a reservoir remains to be characterized. We describe a wild armadillo infected by M.

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A search for alternative treatments led to our interest in the two-component regulator DosRS, which, in , is required for the bacterium to establish a state of nonreplicating, drug-tolerant persistence in response to a variety of host stresses. We show here that the genetic disruption of impairs the adaptation of to hypoxia, resulting in decreased bacterial survival after oxygen depletion, reduced tolerance to a number of antibiotics in vitro and in vivo, and the inhibition of biofilm formation. We determined that three antimalarial drugs or drug candidates, artemisinin, OZ277, and OZ439, can target DosS-mediated hypoxic signaling in and recapitulate the phenotypic effects of genetically disrupting .

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Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae, an obligate intracellular bacterium. Timely detection is a challenge in leprosy diagnosis, relying on clinical examination and trained health professionals. Furthermore, adequate care and transmission control depend on early and reliable pathogen detection.

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Characterizing complex (MABSC) biofilms under host-relevant conditions is essential to the design of informed therapeutic strategies targeted to this persistent, drug-tolerant, population of extracellular bacilli. Using synthetic cystic fibrosis medium (SCFM) which we previously reported to closely mimic the conditions encountered by MABSC in actual cystic fibrosis (CF) sputum and a new model of biofilm formation, we show that MABSC biofilms formed under these conditions are substantially different from previously reported biofilms grown in standard laboratory media in terms of their composition, gene expression profile and stress response. Extracellular DNA (eDNA), mannose-and glucose-containing glycans and phospholipids, rather than proteins and mycolic acids, were revealed as key extracellular matrix (ECM) constituents holding clusters of bacilli together.

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Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions.

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Humans are considered as the main host for Mycobacterium leprae, the aetiological agent of leprosy, but spillover has occurred to other mammals that are now maintenance hosts, such as nine-banded armadillos and red squirrels. Although naturally acquired leprosy has also been described in captive nonhuman primates, the exact origins of infection remain unclear. Here we describe leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in Cantanhez National Park, Guinea-Bissau and Taï National Park, Côte d'Ivoire, West Africa.

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Article Synopsis
  • Hansen's disease (leprosy) has a long history in Europe but is mainly found today in tropical regions, with about 200,000 new cases each year; the genetic history of Mycobacterium leprae is still not fully understood.
  • This study reconstructed 19 ancient M. leprae genomes from various regions in Europe, revealing significant genetic diversity, particularly in leprosaria, and identified a new genotype in Belarus.
  • The research highlights common patterns of strain diversity across Europe, shows that leprosaria were hotspots for this diversity, and provides insights into the historical transmission of the disease.
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Molecular epidemiology investigations are notoriously challenging in the leprosy field mainly because the inherent characteristics of the disease as well as its yet uncultivated causative agents, Mycobacterium leprae and M. lepromatosis. Despite significant developments in understanding the biology of leprosy bacilli through genomic approaches, the exact mechanisms of transmission is still unclear and the factors underlying pathological variation of the disease in different patients remain as major gaps in our knowledge about leprosy.

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Background: Recent advances in sequencing have facilitated large-scale analyses of the metagenomic composition of different samples, including the environmental microbiome of air, water, and soil, as well as the microbiome of living humans and other animals. Analyses of the microbiome of ancient human samples may provide insights into human health and disease, as well as pathogen evolution, but the field is still in its very early stages and considered highly challenging.

Results: The metagenomic and pathogen content of Egyptian mummified individuals from different time periods was investigated via genetic analysis of the microbial composition of various tissues.

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Understanding the physiological processes underlying the ability of to become a chronic pathogen of the cystic fibrosis (CF) lung is important to the development of prophylactic and therapeutic strategies to better control and treat pulmonary infections caused by these bacteria. Gene expression profiling of a diversity of complex isolates points to amino acids being significant sources of carbon and energy for in both CF sputum and synthetic CF medium and to the bacterium undergoing an important metabolic reprogramming in order to adapt to this particular nutritional environment. Cell envelope analyses conducted on the same representative isolates further revealed unexpected structural alterations in major cell surface glycolipids known as the glycopeptidolipids (GPLs).

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Article Synopsis
  • Human settlement in Madagascar began in the first millennium with migrations from Southeast Asia, Africa, and the Middle East, leaving cultural and genetic legacies.
  • The study used whole-genome sequencing to analyze leprosy strains in Madagascar and the Comoros, identifying a new genotype (1D-Malagasy) prevalent in these regions and linked to local public health issues.
  • Findings indicate that leprosy likely originated from later migrations from East Africa, the Middle East, or South Asia, rather than being introduced by the early Austronesian settlers.
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