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Acta Dermato-venereologica Sep 2023
Topics: Humans; Trephining; Hand; Upper Extremity; High-Throughput Nucleotide Sequencing
PubMed: 37731212
DOI: 10.2340/actadv.v103.13360 -
Scientific Reports Sep 2023The β-lactamase of Mycobacterium tuberculosis, BlaC, hydrolyzes β-lactam antibiotics, hindering the use of these antibiotics for the treatment of tuberculosis....
The β-lactamase of Mycobacterium tuberculosis, BlaC, hydrolyzes β-lactam antibiotics, hindering the use of these antibiotics for the treatment of tuberculosis. Inhibitors, such as avibactam, can reversibly inhibit the enzyme, allowing for the development of combination therapies using both antibiotic and inhibitor. However, laboratory evolution studies using Escherichia coli resulted in the discovery of single amino acid variants of BlaC that reduce the sensitivity for inhibitors or show higher catalytic efficiency against antibiotics. Here, we tested these BlaC variants under more physiological conditions using the M. marinum infection model of zebrafish, which recapitulates hallmark features of tuberculosis, including the intracellular persistence of mycobacteria in macrophages and the induction of granuloma formation. To this end, the M. tuberculosis blaC gene was integrated into the chromosome of a blaC frameshift mutant of M. marinum. Subsequently, the resulting strains were used to infect zebrafish embryos in order to test the combinatorial effect of ampicillin and avibactam. The results show that embryos infected with an M. marinum strain producing BlaC show lower infection levels after treatment than untreated embryos. Additionally, BlaC K234R showed higher infection levels after treatment than those infected with bacteria producing the wild-type enzyme, demonstrating that the zebrafish host is less sensitive to the combinatorial therapy of β-lactam antibiotic and inhibitor. These findings are of interest for future development of combination therapies to treat tuberculosis.
Topics: Animals; Mycobacterium tuberculosis; Zebrafish; Mycobacterium marinum; beta-Lactamases; Tuberculosis; Ampicillin; Anti-Bacterial Agents; Escherichia coli
PubMed: 37717068
DOI: 10.1038/s41598-023-42152-8 -
Microbiology Resource Announcements Oct 2023The complete genome sequence of mycobacterial strain YM-3, isolated from cultured yellowtail in 1986, was determined. The strain was , a closely related subspecies of ,...
The complete genome sequence of mycobacterial strain YM-3, isolated from cultured yellowtail in 1986, was determined. The strain was , a closely related subspecies of , so the strain was isolated earlier than the first report of the subspecies in 2005.
PubMed: 37712690
DOI: 10.1128/MRA.00498-23 -
Biomaterials Nov 2023Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant public health threat with high rates of infection and mortality. Rapid and reliable...
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant public health threat with high rates of infection and mortality. Rapid and reliable theranostics of TB are essential to control transmission and shorten treatment duration. In this study, we report two cationic aggregation-inducing emission luminogens (AIEgens) named TTVP and TTPy, which have different functional charged moieties, to investigate their potential for simultaneous tracing and photodynamic therapy in TB infection. TTVP and TTPy exhibit intrinsic positive charges, excellent water solubility, and near-infrared (NIR) emission. Based on ionic-function relationships, TTVP, with more positive charges, demonstrates a stronger binding affinity to Mycobacterium marinum (M.m), (a close genetic relative of Mtb), compared to TTPy. Both TTVP and TTPy exhibit high efficiency in generating reactive oxygen species (ROS) when exposed to white light irradiation, enabling effective photodynamic killing of M.m in vitro. Additionally, we achieved long-term, real-time, noninvasive, continuous tracing, and evaluated therapeutic performance in vivo. Notably, TTVP outperformed TTPy in intracellular killing of M.m, suggesting a possible correlation between the labeling and photodynamic killing abilities of AIEgens. These findings provide valuable insights and a design basis for cationic AIEgens in TB research, offering potential advancements in TB theranostics.
Topics: Humans; Tuberculosis; Photochemotherapy; Mycobacterium tuberculosis; Light; Reactive Oxygen Species
PubMed: 37690379
DOI: 10.1016/j.biomaterials.2023.122301 -
Life Sciences Oct 2023The intracellular production of reactive oxygen species (ROS), composed of oxygen-reduced molecules, is important not only because of their lethal effects on... (Review)
Review
The intracellular production of reactive oxygen species (ROS), composed of oxygen-reduced molecules, is important not only because of their lethal effects on microorganisms but also due to their potential inflammatory and metabolic regulation properties. The ROS pro-inflammatory properties are associated with the second signal to inflammasome activation, leading to cleaving pro-IL-1β and pro-IL18 before their secretion, as well as gasdermin-D, leading to pyroptosis. Some microorganisms can modulate NLRP3 and AIM-2 inflammasomes through ROS production: whilst Mycobacterium bovis, Mycobacterium kansasii, Francisella novicida, Brucella abortus, Listeria monocytogenes, Influenza virus, Syncytial respiratory virus, Porcine reproductive and respiratory syndrome virus, SARS-CoV, Mayaro virus, Leishmania amazonensis and Plasmodium sp. enhance inflammasome assembly, Hepatitis B virus, Mycobacterium marinum, Mycobacterium tuberculosis, Francisella tularensis and Leishmania sp. disrupt it. This process represents a recent cornerstone in our knowledge of the immunology of intracellular pathogens, which is reviewed in this mini-review.
Topics: Swine; Animals; Reactive Oxygen Species; Inflammasomes; Oxygen; Hepatitis B virus; Microbial Interactions
PubMed: 37683723
DOI: 10.1016/j.lfs.2023.122076 -
MBio Oct 2023Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen. , the causative agent, has perfected many ways to replicate...
Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen. , the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the endoplasmic reticulum (ER)-Golgi lipid transfer protein OSBP8 in the / system. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defense mechanism against intracellular pathogens such as .
Topics: Humans; Vacuoles; Dictyostelium; Endoplasmic Reticulum; Mycobacterium marinum; Mycobacterium tuberculosis; Tuberculosis
PubMed: 37676004
DOI: 10.1128/mbio.00943-23 -
Journal of Cutaneous Pathology Dec 2023
Topics: Humans; Mycobacterium marinum; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Granuloma
PubMed: 37669877
DOI: 10.1111/cup.14527 -
Respirology Case Reports Oct 2023is a ubiquitous water-borne non-tuberculous mycobacterial (NTM) pathogen. In humans, infections are acquired through direct inoculation of skin wounds and are almost...
is a ubiquitous water-borne non-tuberculous mycobacterial (NTM) pathogen. In humans, infections are acquired through direct inoculation of skin wounds and are almost exclusively localized to skin and soft tissues. Pulmonary infection with is extremely rare, and to our knowledge, invasive endobronchial disease has not been reported. Here, we present a case of a 71-year-old immunocompetent male surfer with invasive endotracheal granulomatous disease. The patient was successfully cured with a regimen of azithromycin 250 mg daily, ethambutol 900 mg (15 mg/kg) daily and rifampicin 600 mg daily for 12 months following culture conversion. This case highlights several important concepts: Firstly, infection, including invasive endobronchial infection, should be considered a rare cause of NTM pulmonary disease. Secondly, endotracheal infection can be successfully eradicated with this selected therapeutic regimen. Finally, the absence of . skin or soft-tissue infection in this patient, raises the possibility that human disease might also be acquired via inhalation of . contaminated water in rare circumstances.
PubMed: 37664419
DOI: 10.1002/rcr2.1211 -
BioRxiv : the Preprint Server For... Aug 2023Intracellular lipid inclusions (ILI) are triacylglyceride rich organelles produced by mycobacteria thought to serve as energy reservoirs. It is believed that ILI are...
Intracellular lipid inclusions (ILI) are triacylglyceride rich organelles produced by mycobacteria thought to serve as energy reservoirs. It is believed that ILI are formed as a result of a mediated transition from replicative growth to non-replicating persistence (NRP). ILI rich (Mtb) bacilli have been reported during infection and in sputum, establishing their importance in Mtb pathogenesis. Studies conducted in mycobacteria such as or lab Mtb strains have demonstrated ILI formation in the presence of hypoxic, nitric oxide, nutrient limitation, or low nitrogen stress, conditions believed to emulate the host environment within which Mtb resides. Here, we show that and clinical Mtb isolates make ILI during active replication in axenic culture independent of environmental stressors. By tracking ILI formation dynamics we demonstrate that ILI are quickly formed in the presence of fresh media or exogenous fatty acids but are rapidly depleted while bacteria are still actively replicating. We also show that the cell envelope is an alternate site for neutral lipid accumulation observed during stationary phase. In addition, we screen a panel of 60 clinical isolates and observe variation in ILI production during early log phase growth between and among Mtb lineages. Finally, we show that expression level does not strictly correlate with ILI accumulation in fresh clinical isolates. Taken together, our data provide evidence of an active ILI formation pathway in replicating mycobacteria cultured in the absence of stressors, suggesting a decoupling of ILI formation from NRP.
PubMed: 37609245
DOI: 10.1101/2023.08.10.552809 -
The Medical Journal of Australia Sep 2023
Topics: Humans; Mycobacterium Infections, Nontuberculous; Seawater
PubMed: 37593915
DOI: 10.5694/mja2.52069