Pharmacological Poly (ADP-Ribose) Polymerase Inhibitors Decrease Mycobacterium tuberculosis Survival in Human Macrophages

Doorn, Cassandra L.R. van; Steenbergen, Sanne A. M.; Walburg, Kimberley V.; Ottenhoff, Tom H. M.

doi:10.3389/fimmu.2021.712021

Cited by 9 publications

(10 citation statements)

References 63 publications

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“…Con el conocimiento de que el gen regulador eucariótico poli (ADP-ribosa) polimerasa 1 (PARP1) es el primer objetivo huésped de la pirazinamida, y que PARP1 regula procesos celulares fundamentales y funciones inmunitarias, se ha demostrado que inhibidores de PARP1 son capaces de inhibir el crecimiento intracelular de Mycobacterium tuberculosis y dosminuye su supervivencia en macrófagos, por lo que puede ser una terapia prometedora en los pacientes con tuberculosis. 15…”

Section: Discussionunclassified

Tuberculosis abdominal que mimetiza cáncer de ovario. Reporte de una serie de casos

Morales-Castelán¹,

Lara-Hernández²,

Hernández-Nava³

et al. 2022

GMM

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Introducción: La tuberculosis peritoneal (tuberculosis abdominal) puede ser confundida con una neoplasia maligna. Objetivo: Describir características clínicas y demográficas de pacientes con tuberculosis abdominal que semeja cáncer de ovario avanzado, diagnosticados en un centro oncológico de referencia nacional. Métodos: Se describen las características clínicas y patológicas de nueve pacientes con tuberculosis abdominal que clínicamente semejaba cáncer de ovario avanzado. Resultados: La mediana de edad fue de 47 años, el estrato socioeconómico más común fue bajo (44 %). El dolor abdominal y la pérdida ponderal se presentaron en 77.7 %, ascitis en 55.5 %, prueba COMBE positiva en 22.2 % y ausencia de antecedente de tuberculosis pulmonar en 100 %. La elevación de CA-125 se reportó en 77.7 %, con > 500 U/mL en 57.1 %. La tomografía indicó carcinomatosis en 50 % y tumor pélvico y ascitis en 37.5 %. Todas las pacientes fueron sometidas a cirugía; 62.5 % fueron diagnosticadas mediante estudio patológico transoperatorio como enfermedad neoplásica. Conclusión: La tuberculosis es considerada como la gran imitadora, por ello se debe tener en mente el diagnóstico de tuberculosis abdominal ante un caso sospechoso, aun cuando la presentación clínica, estudios de imagen e, incluso, el examen transoperatorio sugieran cáncer de ovario.

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Section: Discussionunclassified

Tuberculosis abdominal que mimetiza cáncer de ovario. Reporte de una serie de casos

Morales-Castelán¹,

Lara-Hernández²,

Hernández-Nava³

et al. 2022

GMM

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“…With the knowledge that eukaryotic regulatory gene poly(ADP-ribose) polymerase 1 (PARP1) is the primary host target of pyrazinamide, and that PARP1 regulates essential cellular processes and immune functions, PARP1 inhibitors have been shown to be able to inhibit Mycobacterium tuberculosis intracellular growth and to decrease its survival in macrophages, and thus it may be a promising therapy in patients with tuberculosis. 15…”

Section: Discussionmentioning

confidence: 99%

Abdominal tuberculosis mimicking ovarian cancer. A case series report

Morales-Castelán¹,

Lara-Hernández²,

Hernández-Nava³

et al. 2022

GMM

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Introduction: Peritoneal tuberculosis (abdominal tuberculosis) can be confused with a malignant neoplasm. Objective: To describe clinical and demographic characteristics of patients with abdominal tuberculosis mimicking advanced ovarian cancer, diagnosed in a national reference cancer center. Methods: Clinical and pathological characteristics of nine patients with abdominal tuberculosis that clinically resembled advanced ovarian cancer are described. Results: Median age was 47 years; the most common socioeconomic status was low (44%). Abdominal pain and weight loss occurred in 77.7%; ascites, in 55.5%; 22.2% had a positive COMBE test, and 100% had no history of pulmonary tuberculosis. CA-125 elevation was reported in 77.7%, with levels > 500 U/mL in 57.1%. Tomography reported carcinomatosis in 50% and pelvic tumor and ascites in 37.5%. All patients underwent surgery, where 62.5% were diagnosed by intraoperative pathology study as neoplastic disease. Conclusion: Tuberculosis is considered the great imitator, which is why abdominal tuberculosis diagnosis should be borne in mind when faced with a suspicious case, even when clinical presentation, imaging studies, and even intraoperative examination suggest ovarian cancer.

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“…In addition, some pathogens can also modulate NAD + metabolism to support their fitness through the activity of pathogenic-specific enzymes such as NADases, or by the modulation of the activity of host NAD + -dependent enzymes (i.e., Sirtuins, PARPs, and CD38) [ 172 , 173 ]. Very recently, the pharmacological inhibition of PARPs in patients affected by diabetes mellitus has been reported to decrease intracellular M. tuberculosis (Mtb) in human macrophages, identifying PARP targeting as a potential novel strategy for host-directed therapy against M. tuberculosis and possibly against other infectious diseases [ 174 ].…”

Section: Exploitation Of Dart/darg Biology For a Rational Design Of A...mentioning

confidence: 99%

The DarT/DarG Toxin–Antitoxin ADP-Ribosylation System as a Novel Target for a Rational Design of Innovative Antimicrobial Strategies

2023

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The chemical modification of cellular macromolecules by the transfer of ADP-ribose unit(s), known as ADP-ribosylation, is an ancient homeostatic and stress response control system. Highly conserved across the evolution, ADP-ribosyltransferases and ADP-ribosylhydrolases control ADP-ribosylation signalling and cellular responses. In addition to proteins, both prokaryotic and eukaryotic transferases can covalently link ADP-ribosylation to different conformations of nucleic acids, thus highlighting the evolutionary conservation of archaic stress response mechanisms. Here, we report several structural and functional aspects of DNA ADP-ribosylation modification controlled by the prototype DarT and DarG pair, which show ADP-ribosyltransferase and hydrolase activity, respectively. DarT/DarG is a toxin–antitoxin system conserved in many bacterial pathogens, for example in Mycobacterium tuberculosis, which regulates two clinically important processes for human health, namely, growth control and the anti-phage response. The chemical modulation of the DarT/DarG system by selective inhibitors may thus represent an exciting strategy to tackle resistance to current antimicrobial therapies.

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Pharmacological Poly (ADP-Ribose) Polymerase Inhibitors Decrease Mycobacterium tuberculosis Survival in Human Macrophages

Cited by 9 publications

References 63 publications

Tuberculosis abdominal que mimetiza cáncer de ovario. Reporte de una serie de casos

Tuberculosis abdominal que mimetiza cáncer de ovario. Reporte de una serie de casos

Abdominal tuberculosis mimicking ovarian cancer. A case series report

The DarT/DarG Toxin–Antitoxin ADP-Ribosylation System as a Novel Target for a Rational Design of Innovative Antimicrobial Strategies

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