Application of Continuous Culture for Assessing Antibiotic Activity Against Mycobacterium tuberculosis

Author(s):  
Charlotte L. Hendon-Dunn ◽  
Saba Anwar ◽  
Christopher Burton ◽  
Joanna Bacon
Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 114 ◽  
Author(s):  
Alfredo F. Braña ◽  
Aida Sarmiento-Vizcaíno ◽  
Ignacio Pérez-Victoria ◽  
Jesús Martín ◽  
Luis Otero ◽  
...  

The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (1), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete Streptomyces althioticus MSM3, isolated from samples of the intertidal seaweed Ulva sp. collected in the Cantabrian Sea (Northeast Atlantic Ocean). Particularly interesting is its strong antibiotic activity against Mycobacterium tuberculosis clinical isolates, resistant to antibiotics in clinical use. To the best of our knowledge, this is the first report on a member of the desertomycin family displaying such activity. Additionally, desertomycin G shows strong antibiotic activities against other relevant Gram-positive clinical pathogens such as Corynebacterium urealyticum, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecium, Enterococcus faecalis, and Clostridium perfringens. Desertomycin G also displays moderate antibiotic activity against relevant Gram-negative clinical pathogens such as Bacteroides fragilis, Haemophilus influenzae and Neisseria meningitidis. In addition, the compound affects viability of tumor cell lines, such as human breast adenocarcinoma (MCF-7) and colon carcinoma (DLD-1), but not normal mammary fibroblasts.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1071
Author(s):  
Erika A. Peláez Coyotl ◽  
Jacqueline Barrios Palacios ◽  
Gabriel Muciño ◽  
Daniel Moreno-Blas ◽  
Miguel Costas ◽  
...  

Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process. Previous studies have reported that autophagy-activating agents eliminate intracellular MDR MTB. Thus, combining a direct antibiotic activity against circulating bacteria with autophagy activation to eliminate bacteria residing inside cells could treat MDR TB. We show that the synthetic peptide, IP-1 (KFLNRFWHWLQLKPGQPMY), induced autophagy in HEK293T cells and macrophages at a low dose (10 μM), while increasing the dose (50 μM) induced cell death; IP-1 induced the secretion of TNFα in macrophages and killed Mtb at a dose where macrophages are not killed by IP-1. Moreover, IP-1 showed significant therapeutic activity in a mice model of progressive pulmonary TB. In terms of the mechanism of action, IP-1 sequesters ATP in vitro and inside living cells. Thus, IP-1 is the first antimicrobial peptide that eliminates MDR MTB infection by combining four activities: reducing ATP levels, bactericidal activity, autophagy activation, and TNFα secretion.


2015 ◽  
Vol 93 (11) ◽  
pp. 1305-1311 ◽  
Author(s):  
Alyssa E. Patterson ◽  
Andrew J. Flewelling ◽  
Trevor N. Clark ◽  
Stephen J. Geier ◽  
Christopher M. Vogels ◽  
...  

Ten lipophilic amines were prepared from the reductive amination of vanillin and the corresponding primary amines using sodium borohydride in methanol. All compounds have been obtained elementally pure and an X-ray diffraction study on the 4-n-butylaniline derivative has confirmed the molecular structure. Whilst the overall antibiotic activity of the derivatives was low, some of these compounds, particularly the boronate ester 2-methoxy-4-((2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamino)methyl)phenol (7), showed a promising degree of antimycobacterial activity against Mycobacterium tuberculosis H37Ra, where activity seemed to vary by the position of the boron substitution on the aniline ring.


2015 ◽  
Vol 6 ◽  
Author(s):  
Tatiane Coelho ◽  
Diana Machado ◽  
Isabel Couto ◽  
Raquel Maschmann ◽  
Daniela Ramos ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Christoph Hölscher ◽  
Jessica Gräb ◽  
Alexandra Hölscher ◽  
Annie Linnea Müller ◽  
Stephan C. Schäfer ◽  
...  

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