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.

A single dose of TELACEBEC (Q203), a phase 2 clinical candidate for tuberculosis, eradicates Mycobacterium ulcerans in a mouse model of Buruli ulcer infection without relapse up to 19 weeks post treatment. Clinical use of Q203 could dramatically simplify the clinical management of Buruli ulcer, a neglected mycobacterial disease.

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.

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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.

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