Lung cancer: a new frontier for microbiome research and clinical translation.

The lung microbiome has been shown to reflect a range of pulmonary diseases-for example: asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Studies have now begun to show microbiological changes in the lung that correlate with lung cancer (LC) which could provide new insights into lung carcinogenesis and new biomarkers for disease screening. Clinical studies have suggested that infections with tuberculosis or pneumonia increased the risk of LC possibly through inflammatory or immunological changes. These have now been superseded by genomic-based microbiome sequencing studies based on bronchoalveolar lavage, sputum or saliva samples. Although some discrepancies exist, many have suggested changes in particular bacterial genera in LC samples particularly, Granulicatella, Streptococcus and Veillonella. Granulicatella is of particular interest, as it appeared to show LC stage-specific increases in abundance. We propose that these microbial community changes are likely to reflect biochemical changes in the LC lung, linked to an increase in anaerobic environmental niches and altered pyridoxal/polyamine/nitrogenous metabolism to which Granulicatella could be particularly responsive. These are clearly preliminary observations and many more expansive studies are required to develop our understanding of the LC microbiome.

Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.

Enemy at the gates: interaction-specific stomatal responses to pathogenic challenge.

Stomata regulate gas exchange and their closure in response to pathogens may, in some cases, contribute to resistance. However, in the cereal mildew and rust systems, stomatal closure follows establishment of compatible infections. In incompatible systems, expression of major (R) gene controlled hypersensitive responses (HR), causes drastic, permanent stomatal dysfunction: stomata become locked open following powdery mildew attack and locked shut following rust attack. Thus, stomatal locking can be a hitherto unsuspected negative consequence of R gene resistance that carries a physiological cost affecting plant performance.