Evaluation of nitroxyl donors' effect on mycobacteria

Reactive nitrogen and oxygen species: Friend or foe in the tuberculosis fight

“…We have read with great joy the letter to the editor, written by Yew et al, which analyzes and compares several recent articles [1][2][3][4] showing the intimate relationship between Mycobacterium tuberculosis' (Mtb) redox status -mainly due to the presence of Reactive Nitrogen and Oxygen Species (RNOS) -and tubercular drug efficacy. Given the fact that tuberculosis (TB) is an infectious disease for which there is a limited arsenal of effective drugs, it is crucial to find new drugs or to somehow enhance pre-existing treatments.…”

“…as well as NO) exerts a mycobactericidal effect[1] even when it is applied in successive sub-inhibitory doses.Another important but still poorly understood issue related to RNOS and Mtb, are the molecular mechanisms underlying the observed effects. From a biochemical point of view, the molecular mechanisms of Mtb's RNOS defense mediated by key proteins such as superoxide dismutase, catalase, alkylhydroperoxide reductases and the truncated hemoglobin N, among others, are well established [8].…”

Azanone (HNO): generation, stabilization and detection

“…21 In addition to these biological effects, HNO has also been shown to affect mycobacterium tuberculosis growth by interfering with its general physiological state. 22 Another therapeutic application for HNO in the cardiovascular system is its use as a powerful preconditioning agent, which helps to alleviate the negative consequences of an ischemic event and the consequent reperfusion injury. This injury is characterized by blood flow deprivation followed by necrosis and possible heart tissue hypoxia.…”

S -Nitrosated alpha-1-acid glycoprotein exhibits antibacterial activity against multidrug-resistant bacteria strains and synergistically enhances the effect of antibiotics

“…[10][11][12] However, NO is highly reactive with a short biological halflife. 15 Alpha-1-acid glycoprotein (AGP), an acute-phase protein, is mainly produced in the liver. It is well known that S-nitrosothiols, a stable NO reservoir, have a 10 2 -to 10 3 -fold stronger antimicrobial activity than NO alone.…”

“…Interestingly, delamanid, a new antituberculosis medication, possesses the proposed mechanism of action involving intracellular NO release. 15 Alpha-1-acid glycoprotein (AGP), an acute-phase protein, is mainly produced in the liver. It is also produced by immune cells, such as monocytes and macrophages, primarily during inflammation, resulting in locally high AGP concentrations at inflammatory sites.…”