COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe-COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe-host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.
Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical skin disease that is most commonly found in children from West and Central Africa. Despite the severity of the infection, therapeutic options are limited to antibiotics with severe side effects. Here, we show that M. ulcerans is susceptible to the anti-tubercular drug Q203 and related compounds targeting the respiratory cytochrome bc1:aa3. While the cytochrome bc1:aa3 is the primary terminal oxidase in Mycobacterium tuberculosis, the presence of an alternate bd-type terminal oxidase limits the bactericidal and sterilizing potency of Q203 against this bacterium. M. ulcerans strains found in Buruli ulcer patients from Africa and Australia lost all alternate terminal electron acceptors and rely exclusively on the cytochrome bc1:aa3 to respire. As a result, Q203 is bactericidal at low dose against M. ulcerans replicating in vitro and in mice, making the drug a promising candidate for Buruli ulcer treatment.
Pulmonary infections caused by are emerging as a global threat, especially in cystic fibrosis patients. Further intensifying the concern of infection is the recent evidence of human-to-human transmission of the infection. is a naturally multidrug-resistant fast-growing pathogen for which pharmacological options are limited. Repurposing antitubercular drugs represents an attractive option for the development of chemotherapeutic alternatives against infections. Bedaquiline (BDQ), an ATP synthase inhibitor, has recently been approved for the treatment of multidrug-resistant tuberculosis. Herein, we show that BDQ has a very low MIC against a vast panel of clinical isolates. Despite being bacteriostatic , BDQ was highly efficacious in a zebrafish model of infection. Remarkably, a very short period of treatment was sufficient to protect the infected larvae from -induced killing. This was corroborated with reduced numbers of abscesses and cords, considered to be major pathophysiological signs in infected zebrafish. Mode-of-action studies revealed that BDQ triggered a rapid depletion of ATP in, consistent with the drug targeting the FF ATP synthase. Importantly, despite a failure to select for spontaneous mutants that are highly resistant to BDQ, the transfer of single nucleotide polymorphisms leading to D29V or A64P substitutions in conferred high resistance, thus resolving the target of BDQ in Overall, this study indicates that BDQ is active against and and should be considered for clinical use against the difficult-to-manage pulmonary infections.
Complement component 3 glomerulopathy (C3G) is a recently defined entity comprising of dense deposit disease and C3 glomerulonephritis. The key histological feature is the presence of isolated C3 deposits without immunoglobulins. Often masqueradng as some of the common glomerulonephritides this is a prototype disorder occurring from dysregulated alternate complement pathway with recently identified genetic defects and autoantibodies. We review the pathophysiology, clinical features, and diagnostic and treatment strategies.
The treatment of leprosy is long and complex, benefiting from the development of sterilizing, rapidly-acting drugs. Reductive evolution made Mycobacterium leprae exquisitely sensitive to Telacebec, a phase 2 drug candidate for tuberculosis . The unprecedented potency of Telacebec against M. leprae warrants further validation in clinical trials.
Background: Indigenous Australians are disproportionately affected by end stage kidney disease. Despite this, they face significant delays being assessed and waitlisted for kidney transplant.Aims: To examine the kidney transplant waitlisting process in our region, to compare the workup process between Indigenous Australians and non-Indigenous patients, and identify major sources of delay.Methods: We analysed the records of all patients being treated by our service who were on the kidney transplant waitlist between January 2017 and June 2018. Between-group differences were used to compare the time between commencement of dialysis and completion of each component of assessment. Patients who had more than 1 year between commencement of dialysis and waitlisting were further analysed for major sources of delay.Results: Twenty-five patients were included (20 Indigenous Australians and 5 non-Indigenous). The median time to waitlisting for transplant after commencing dialysis was significantly longer in the Indigenous group (1215 vs 264 days, P = 0.032). Indigenous Australian patients waited longer before commencing the transplant assessment process and before completing dental assessment, tissue typing and review by the transplant nephrologist and surgeon. Five patients (two Indigenous Australians, three non-Indigenous) were waitlisted within 1 year of commencing dialysis. Among the remaining 20 patients, cardiac and systems issues were the two most common major sources of delay. Conclusion:Indigenous Australian patients face significant delays accessing the kidney transplant waitlist. Cardiac assessment and systems issues are prominent sources of delay and efforts to address these areas may help to improve equity of access to kidney transplantation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.