Papers by Claudia Argüelles
Memórias do Instituto Oswaldo Cruz, 2020
Bacillus Calmette Guerin (BCG) vaccines comprise a family of related strains. Whole genome sequen... more Bacillus Calmette Guerin (BCG) vaccines comprise a family of related strains. Whole genome sequencing has allowed the better characterisation of the differences between many of the BCG vaccines. As sequencing technologies improve, updating of publicly available sequence data becomes common practice. We hereby announce the draft genome of four commonly used BCG vaccines in Brazil, Argentina and Venezuela.

Infection and Drug Resistance, 2021
Purpose Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the only vaccine licensed against t... more Purpose Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the only vaccine licensed against tuberculosis. Despite the protection offered by the vaccine, in some circumstances children and immunocompromised individuals can develop associated infections, known as BCGitis. Drug susceptibility patterns of BCG clinical strains have rarely been described. We aimed to describe the susceptibility pattern of BCG clinical strains isolated in two different countries. Methods We performed culture-based drug susceptibility testing of thirty one BCG strains isolated from patients in Brazil (n=5, 16%) and Argentina (n=26, 84%) using the broth micro-dilution method (phenotypic method). Final antibiotic concentrations for susceptibility testing ranged from 0.5 to 16 mg/L for amikacin, 0.3125 to 10 mg/L for ethambutol, 0.05 to 1.6 mg/L for isoniazid and 0.25 to 8 mg/L for rifampicin, streptomycin and ofloxacin. Additionally, we compared the results with genetic data obtained by whole genome seque...

The British Journal of Radiology, 2021
We previously demonstrated, for the first time, the abscopal effect of Boron Neutron Capture Ther... more We previously demonstrated, for the first time, the abscopal effect of Boron Neutron Capture Therapy (BNCT) in an ectopic model of syngeneic colon cancer in BDIX rats. Objective: The aim of the present study was to evaluate the local and regional therapeutic efficacy and abscopal effect of BNCT mediated by boronophenyl-alanine, combined with Bacillus Calmette-Guerin (BCG) as an immunotherapy agent in this model. Methods: The local effect of treatment was evaluated in terms of tumor response in the irradiated tumor-bearing right hind flank. Metastatic spread to tumor-draining lymph nodes was analyzed as an indicator of regional effect. The abscopal effect of treatment was assessed as tumor growth inhibition in the contralateral (non-irradiated) left hind flank inoculated with tumor cells 2 weeks post-irradiation. The experimental groups BNCT, BNCT + BCG, BCG, Beam only (BO), BO +BCG, SHAM (tumor-bearing, no treatment, same manipulation) were studied. Results: BNCT and BNCT + BCG indu...

American Journal of Respiratory and Critical Care Medicine, 2009
Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity aga... more Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. Methods: For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Measurements and Main Results: Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. Conclusions: The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.

La tuberculosis (TB) es una enfermedad pulmonar o generalizada causada por micobacterias del comp... more La tuberculosis (TB) es una enfermedad pulmonar o generalizada causada por micobacterias del complejo Mycobacterium tuberculosis (M.tuberculosis), siendo el M.tuberculosis el agente mas comun en humanos. Es una de las enfermedades mas antiguas que afecta al hombre y hoy en dia continua siendo una de las que causa mas morbi-mortalidad en el mundo. Es por esto que un diagnostico rapido, accesible y confiable es una de las prioridades en la lucha contra la TB. La “antigua” o “vieja” Tuberculina (OT, del nombre en ingles Old Tuberculin), introducida por Koch (un filtrado del caldo de cultivo de M.tuberculosis) y posteriormente el Derivado Proteico Purificado (Tuberculina mejorada por Florence Seibert), fueron utilizados por muchos anos en pruebas cutaneas como herramienta diagnostica. En la actualidad, como alternativa a esta prueba, se han aprobado pruebas ex vivo basadas en el principio de que celulas T de individuos sensibilizados con antigenos de M.tuberculosis producen interferon g...
Revista Argentina de microbiología

Revista Argentina de microbiología
The bacillus Calmette-Guérin (BCG) was obtained in 1920 after successive passages leading to the ... more The bacillus Calmette-Guérin (BCG) was obtained in 1920 after successive passages leading to the attenuation of a Mycobacterium bovis strain. For the following 40 years, BCG had been replicated, resulting in substrains with genotypic and phenotypic differences. Several genomic studies have compared two BCG strains, M. bovis and Mycobacterium tuberculosis, and observed that deleted regions in the different strains could be related to differences in antigenic properties. In this work, a working seed lot was obtained from a lyophilized secondary seed lot from the BCG Pasteur strain 1173 P2 and genetically characterized. The genome was analyzed by PCR directed to five regions (RD1, RD2, RD14, RD15, DU2), using the seed lot and different available strains as templates. No genetic differences were found in the fragments studied as compared to the Pasteur strain. A total of 20 passages were carried out and no differences were found in the size of the fragments amplified by PCR. In conclusi...
International Journal of Molecular Medicine, 2007
Revista Argentina de microbiología

American Journal of Respiratory and Critical Care Medicine, 2009
Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathog... more Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.
Uploads
Papers by Claudia Argüelles