Articles you may be interested inA semiempirical theoretical study of the [2+2] cycloaddition between ketene and formaldehyde AIP Conf. Proc. 330, 222 (1995); 10.1063/1.47652 Molecular beam electric resonance study of the ground and excited states of cyanoacetylene

Two new drugs, delamanid and bedaquiline, have recently been approved for treatment of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis. Here, we report a case of clofazimine, bedaquiline, and low-level delamanid resistances acquired during treatment of a patient with XDR tuberculosis.

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Bedaquiline as a potential agent in the treatment of Mycobacterium abscessus infections To the Editor: Mycobacterium abscessus is increasingly being recognised as a significant human pathogen, especially in patients with cystic fibrosis, and the specific M. abscessus subspecies seems to influence the clinical outcome [1]. The pulmonary manifestation of this nontuberculous mycobacteria (NTM) infection is one of the most difficult to treat forms, leading to substantial morbidity and mortality in this population [1, 2]. M. abscessus strains are highly resistant to most antibacterial drugs [2]. The recent development of liposomal amikacin for inhalation for patients with cystic fibrosis suggested a therapeutic breakthrough. However, even though sputum conversion was improved in a phase 2 study, the primary end-point (change from baseline to day 84 on a semi-quantitative mycobacterial growth scale) was not reached [3]. We analysed the minimal inhibitory concentration (MIC) of another promising new anti-tuberculous drug, bedaquiline, using 20 clinical isolates of M. abscessus. No systematic studies on the distribution of MIC for M. abscessus have been performed previously. Bedaquiline is a diarylquinoline drug recently licensed for the treatment of multidrug-resistant Mycobacterium tuberculosis infections. It acts through inhibition of the mycobacterial F 1 F 0-ATP synthase, [4] and is characterised by excellent intracellular bactericidal activity and a high accumulation rate [4]. In previous studies, bedaquiline showed excellent in vitro activity against M. tuberculosis, including multidrug-resistant strains [5]. The new drug has been successfully and safely used in the treatment of both adult and paediatric multidrug-resistant and extensively drug-resistant tuberculosis alike [6, 7], even over extended periods of as long as 18 months [8]. As for other NTM, in vitro drug susceptibility testing of M. abscessus strains using conventional drugs is recommended only after treatment failure occurs [2]. We present the in vitro bedaquiline MIC results of 20 clinical strains of M. abscessus isolated in our centre between 2011 and 2016 from patients with pulmonary NTM disease, including three patients with cystic fibrosis. In this study, 4/20 strains (20%) were classified as M. abscessus subspecies bolletii, while all others belonged to the M. abscessus subspecies abscessus. The thirdM. abscessus subspecies, M. abscessus subspecies massiliense was not identified among our strains. MIC was determined by a modified agar dilution method on Middlebrook 7H10 agar, as described previously [9]. MIC was defined as the lowest drug concentration that inhibited at least 99% of the bacterial proportion after a twofold serial dilution of the respective drug (MIC99). Results are shown in table 1. All M. abscessus strains tested exhibited a MIC for bedaquiline of ⩽1 µg•mL −1 , and 17/20 (85%) had a MIC of ⩽0.5 µg•mL −1. Median MIC for all M. abscessus strains was 0.5 µg•mL −1 , only slightly higher than that for M. tuberculosis (0.4 µg•mL −1)...

A general strategy and a specific tactic for affinity purification of polypeptides synthesized on solid supports are desbribed and demonstrated. The desired peptide chains were distinguished from terminated peptide chains before removal from the support by attachment of an affinity reagnet (cysteinyl-methionine) bearing an affinity group (thiol) and a binding group (carboxylic acid). After cleavage from the synthetic support, the affinity-labeled peptides (Cys-Met-peptides) were bound to an affinity receptor (organomercurial-agarose) and thus separated from terminated peptides and all other peptides lacking the affinity group. The desired synthetic peptide was obtained by separation of the affinity reagent (loss of Cys-Met by cyanogen bromide cleavage). This general affinity purification strategy is independent of the length or amino acid sequence of the desired peptide. After assembly of ribonuclease-(111-124)-tetradecapeptide, using radiolabeled acetic anhudride for termination of uncoupled in termediates, essentially all (greater than 98.5%) of the acetylated delection peptides were removed by employing the organomercurial Cys-Met tactic. Similarly, the purity of crude synthetic histone H4-(1-37)-heptatriacontapeptide was increased six-fold by using this tactic to remove terminated peptides. A related dimeric Cys-Met tactic is outlined for affinity purification of peptides containing internal cysteine and methionine residues.