The Effect of CFTR Modulators on Airway Infection in Cystic Fibrosis.

The advent of Cystic fibrosis transmembrane receptor (CFTR) modulators in 2012 was a critical event in the history of cystic fibrosis (CF) treatment. Unlike traditional therapies that target downstream effects of CFTR dysfunction, CFTR modulators aim to correct the underlying defect at the protein level. These genotype-specific therapies are now available for an increasing number of CF patients, transforming the way we view the condition from a life-limiting disease to one that can be effectively managed. Several studies have demonstrated the vast improvement CFTR modulators have on normalization of sweat chloride, CFTR function, clinical endpoints, and frequency of pulmonary exacerbation. However, their impact on other aspects of the disease, such as pathogenic burden and airway infection, remain under explored. Frequent airway infections as a result of increased susceptibility and impaired innate immune response are a serious problem within CF, often leading to accelerated decline in lung function and disease progression. Current evidence suggests that CFTR modulators are unable to eradicate pathogenic organisms in those with already established lung disease. However, this may not be the case for those with relatively low levels of disease progression and conserved microbial diversity, such as young patients. Furthermore, it remains unknown whether the restorative effects exerted by CFTR modulators extend to immune cells, such as phagocytes, which have the potential to modulate the response of people with CF (pwCF) to infection. Throughout this review, we look at the potential impact of CFTR modulators on airway infection in CF and their ability to shape impaired pulmonary defences to pathogens.

COVID-19 Spotlights Connections between Disease and Multiple Lifestyle Factors.

The SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus 2), and the disease it causes (COVID-19), have had a profound impact on global human society and threaten to continue to have such an impact with newly emerging variants. Because of the widespread effects of SARS-CoV-2, understanding how lifestyle choices impact the severity of disease is imperative. This review summarizes evidence for an involvement of chronic, non-resolving inflammation, gut microbiome disruption (dysbiosis with loss of beneficial microorganisms), and impaired viral defenses, all of which are associated with an imbalanced lifestyle, in severe disease manifestations and post-acute sequelae of SARS-CoV-2 (PASC). Humans' physiological propensity for uncontrolled inflammation and severe COVID-19 are briefly contrasted with bats' low propensity for inflammation and their resistance to viral disease. This insight is used to identify positive lifestyle factors with the potential to act in synergy for restoring balance to the immune response and gut microbiome, and thereby protect individuals against severe COVID-19 and PASC. It is proposed that clinicians should consider recommending lifestyle factors, such as stress management, balanced nutrition and physical activity, as preventative measures against severe viral disease and PASC.

Bacterial Outer Membrane Vesicles: Role in Pathogenesis and Host-Cell Interactions.

Outer membrane vesicles (OMVs) are small, spherical structures released from the outer membranes of Gram-negative bacteria into the surrounding environment. Investigations into OMVs range from their biogenesis and cargo composition to their ability to transfer virulence factors and modulate host immune responses. This emerging understanding of OMVs has unveiled their pivotal role in the pathogenicity of infectious diseases, shedding light on their interactions with host cells, their contributions to inflammation, their potential involvement in antimicrobial resistance, and their promising use for the development of novel treatments and therapies. Numerous studies have associated the OMVs of pathogenic bacteria with the exacerbation of inflammatory diseases, underlining the significance of understanding the mechanisms associated with these vesicles to find alternatives for combating these conditions. Additionally, OMVs possess the ability to act as decoys, absorbing and neutralizing antibiotics, which significantly diminishes the efficacy of a broad spectrum of antimicrobial agents. Another subtopic of interest is OMVs produced by commensal microbiota. These vesicles are increasingly acknowledged for their mutualistic functions, significantly influencing their host's physiology and immune responses. Consequently, OMVs play a crucial role in maintaining a balanced gut microbiota by fostering symbiotic relationships that significantly contribute to the overall health and well-being of the host. This comprehensive review aims to provide an up-to-date review of OMVs derived from Gram-negative bacteria, summarizing current research findings, and elucidating the multifaceted role of these vesicles in diverse biological contexts.