Multi-strain probiotics are widely regarded as effective products for improving gut microbiota stability and host health, providing advantages over single-strain probiotics. However, in general, it is unclear to what extent different strains would cooperate or compete for resources, and how the establishment of a common biofilm microenvironment could influence their interactions. In this work, we develop an integrative experimental and computational approach to comprehensively assess the metabolic functionality and interactions of probiotics across growth conditions. Our approach combines co-culture assays with genome-scale modelling of metabolism and multivariate data analysis, thus exploiting complementary data- and knowledge-driven systems biology techniques. To show the advantages of the proposed approach, we apply it to the study of the interactions between two widely used probiotic strains of Lactobacillus reuteri and Saccharomyces boulardii, characterising their production potential for compounds that can be beneficial to human health. Our results show that these strains can establish a mixed cooperative-antagonistic interaction best explained by competition for shared resources, with an increased individual exchange but an often decreased net production of amino acids and short-chain fatty acids. Overall, our work provides a strategy that can be used to explore microbial metabolic fingerprints of biotechnological interest, capable of capturing multifaceted equilibria even in simple microbial consortia.

The present study represents a genome-wide transcriptomic analysis of the response of the model streptomycete Streptomyces coelicolor A3(2) M145 to fermentor culture in Modified Evans Media limited, respectively, for nitrogen, phosphate and carbon undertaken as part of the ActinoGEN consortium to provide a publicly available reference microarray dataset.

Heather honey was tested for its effect on the formation of biofilms by Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Salmonella Enteriditis and Acinetobacter baumanii in comparison with Manuka honey. At 0.25 mg/mL, Heather honey inhibited biofilm formation in S. aureus, A. baumanii, E. coli, S. Enteriditis and P. aeruginosa, but promoted the growth of E. faecalis and K. pneumoniae biofilms. Manuka honey inhibited biofilm formation in K. pneumoniae, E. faecalis, and S. Enteriditis, A. baumanii, E. coli and P. aeruginosa, but promoted S. aureus biofilm formation. Molecular docking with Autodock Vina was performed to calculate the predictive binding affinities and ligand efficiencies of Manuka and Heather honey constituents for PaDsbA1, the main enzyme controlling the correct folding of virulence proteins in Pseudomonas aeruginosa. A number of constituents, including benzoic acid and methylglyoxal, present in Heather and/or Manuka honey, revealed high ligand efficiencies for the target enzyme. This helps support, to some extent, the decrease in P. aeruginosa biofilm formation observed for such honeys.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are important human pathogens and a significant health hazard for hospitals and the food industry. They are resistant to β-lactam antibiotics including methicillin and extremely difficult to treat. In this study, we show that the Staphylococcus aureus COL (MRSA) strain, with a known complete genome, can easily survive and grow under acidic and alkaline conditions (pH5 and pH9, respectively), both planktonically and as a biofilm. A microarray-based analysis of both planktonic and biofilm cells was performed under acidic and alkaline conditions showing that several genes are up- or down-regulated under different environmental conditions and growth modes. These genes were coding for transcription regulators, ion transporters, cell wall biosynthetic enzymes, autolytic enzymes, adhesion proteins and antibiotic resistance factors, most of which are associated with biofilm formation. These results will facilitate a better understanding of the physiological adjustments occurring in biofilm-associated S. aureus COL cells growing in acidic or alkaline environments, which will enable the development of new efficient treatment or disinfection strategies.

Probiotics are bacterial strains that are known to provide host health benefits. Limosilactobacillus reuteri is a well-documented lactic acid bacterium that has been cultured from numerous human sites. The strain investigated was L. reuteri DSM 20016, which has been found to produce useful metabolites. The strain was explored using genomic and proteomic tools, manual searches, and databases, including KEGG, STRING, BLAST Sequence Similarity Search, and UniProt. This study located over 200 key genes that were involved in human health benefit pathways. L. reuteri DSM 20016 has metabolic pathways to produce acetate, propionate, and lactate, and there is evidence of a pathway for butanoate production through a FASII mechanism. The bacterium produces histamine through the hdc operon, which may be able to suppress proinflammatory TNF, and the bacterium also has the ability to synthesize folate and riboflavin, although whether they are secreted is yet to be explored. The strain can bind to human Caco2 cells through srtA, mapA/cnb, msrB, and fbpA and can compete against enteric bacteria using reuterin, which is an antimicrobial that induces oxidative stress. The atlas could be used for designing metabolic engineering approaches to improve beneficial metabolite biosynthesis and better probiotic-based cures.

This study aims to establish whether commercially available food oils can be used by Streptomyces clavuligerus as sole carbon sources for growth and clavulanic acid production. Batch cultures in bioreactors showed that Strep. clavuligerus growth and clavulanic acid yields in a P-limited medium containing 0.6% (v/v) olive oil were respectively 2.5- and 2.6-fold higher than in a glycerol-containing medium used as control. Glycerol- and olive oil-grown cells present different macromolecular composition, particularly lipid and protein content. Streptomyces clavuligerus uses olive oil as the sole carbon and energy source for growth and clavulanic acid production. Yields and production rates in olive oil are comparable to those reported for oil-containing complex media. Differences in yields and in the macromolecular composition indicate that different metabolic pathways convert substrate into product. This is the first report of oils being used as the sole carbon source by Strep. clavuligerus. Apart from economic benefits, interesting questions are raised about Strep. clavuligerus physiology. Defined culture media allow physiological studies to be performed in the absence of interference by other compounds. Understanding how Strep. clavuligerus catabolises oils may have an economic impact in clavulanic acid production.