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Chronic obstructive pulmonary disease (COPD) and bronchiectasis represent chronic airway diseases associated with significant morbidity and mortality. Bacteria and viruses are commonly implicated in acute exacerbations; however the significance of fungi in these airways remains poorly defined. While COPD and bronchiectasis remain recognized risk factors for the occurrence of Aspergillus-associated disease including chronic and invasive aspergillosis, underlying mechanisms that lead to the progression from colonization to invasive disease remain uncertain. Nonetheless, advances in molecular technologies have improved our detection, identification and understanding of resident fungi characterizing these airways. Mycobiome sequencing has revealed the complex varied and myriad profile of airway fungi in COPD and bronchiectasis, including their association with disease presentation, progression, and mortality. In this review, we outline the emerging evidence for the clinical importance of fungi in COPD and bronchiectasis, available diagnostic modalities, mycobiome sequencing approaches and association with clinical outcomes.

Aspergillus terreus species complex is an opportunistic fungal pathogen increasingly implicated in invasive infection, as well as chronic respiratory disease. Currently, an understanding of A. terreus pathogenicity is impeded by a limited number of whole-genome sequences of this fungal pathogen. We here describe a high-quality whole-genome assembly of European A. terreus clinical isolate M6925, derived by single-molecule real-time sequencing with short-read polishing.

The wider availability of information on genomes has become essential for future advances in fungal biology, pathogenesis and epidemiology, and for the discovery of new drugs and diagnostics. MycopathologiaGENOMES is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.

Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( https://integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced diversity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than individual microbes, providing a fresh approach to the understanding of respiratory infection. Ministry of Health (MOH) Nanyang Technological University This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Transition Award (NMRC/TA/0048/2016 to S.H.C.); the Clinician-Scientist Individual Research Grant (MOH-000141 to S.H.C.); NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS) (NIM/03/2018 to S.H.C.); the British Lung Foundation through the GSK/British Lung Foundation Chair of Respiratory Research (to J.D.C.) and the Scottish Government Chief Scientist Office (SCAF/17/03). K.T.-A. gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1.

Pseudomonas aeruginosa is a major pathogen responsible for both acute and chronic infection. Known as a colonising pathogen of the cystic fibrosis (CF) lung, it is implicated in other settings such as bronchiectasis. It has the ability to cause acute disseminated or localised infection particularly in the immunocompromised. Human hormones have been highlighted as potential regulators of bacterial virulence through crosstalk between analogous "quorum sensing" (QS) systems present in the bacteria that respond to mammalian hormones. Pseudomonas aeruginosa is known to utilise interconnected QS systems to coordinate its virulence and evade various aspects of the host immune system activated in response to infection. Several human hormones demonstrate an influence on P. aeruginosa growth and virulence. This inter-kingdom signalling, termed "microbial endocrinology" has important implications for host-microbe interaction during infection and, potentially opens up novel avenues for therapeutic intervention. This phenomenon, supported by the existence of sexual dichotomies in both microbial infection and chronic lung diseases such as CF is potentially explained by sex hormones and their influence on the infective process. This review summarises our current understanding of the microbial endocrinology of P. aeruginosa, including its endogenous QS systems and their intersection with human endocrinology, pathogenesis of infection and the host immune system.

Background Non-tuberculous mycobacteria (NTM) infection is an increasing problem worldwide. The epidemiology of NTM in most Asian countries is unknown. This study investigated the epidemiology, and clinical profile of inpatients in whom NTM was isolated from various anatomical sites in a Singaporean population attending a major tertiary referral centre. Methods Demographic profile, clinical data, and characteristics of patients hospitalized with NTM isolates at a major tertiary hospital over two-year period were prospectively assessed (2011–2012). Data collected included patient demographics, ethnicity, smoking status, co-morbidities, NTM species, intensive care unit (ICU) treatment, and mortality. Results A total of 485 patients (62.1% male) with 560 hospital admissions were analysed. The median patient age was 70 years. Thirteen different NTM species were isolated from this cohort. Mycobacterium abscessus (M. abscessus) (38.4%) was most frequently isolated followed by Mycobacterium fortuitum (M. fortuitum) (16.6%), Mycobacterium avium complex (MAC) (16.3%), Mycobacterium kansasii (M. kansasii) (15.4%), and Mycobacterium gordonae (M. gordonae) (6.8%). Most (91%) NTM was isolated from the respiratory tract. The three most common non-pulmonary sites were; blood (2.7%), skin wounds and abscesses (2.1%), and gastric aspirates (1.1%). A third (34.4%) of the study population had prior pulmonary tuberculosis (PTB). There was a significant association between isolated NTM species, and patient age (p=0.0002). Eleven (2.2%) patients received intensive care unit (ICU) treatment during the study period and all cause mortality within 1 year of the study was 16.9% (n=82). Of these, 72 (87.8%) patients died of pulmonary causes. Conclusions The profile of NTM species in Singapore is unique. M. abscessus is the commonest NTM isolated, with a higher prevalence in males, and in the elderly. High NTM prevalence is associated with high rates of prior PTB in our cohort. Published version

Patients with cystic fibrosis (CF) suffer from chronic airway infection and inflammation. Traditionally, bacteria have been regarded the main CF pathogens while fungi have emerged and more recently warranted greater attention. Fungi are increasingly found to colonize CF airways; however, their precise clinical impact continues to spark controversy. While the clinical relevance of allergic bronchopulmonary aspergillosis (ABPA) in CF has been established, the roles of non-ABPA Aspergillus fumigatus, Candida albicans, and other more rare emerging fungi remain poorly understood. Here, we summarize and discuss recent findings in this field and refer toward unresolved questions.