Phosphorothioate-DNA bacterial diet reduces the ROS levels in C. elegans while improving locomotion and longevity

DNA phosphorothioation (PT) is widely distributed in the human gut microbiome. In this work, PT-diet effect on nematodes was studied with PT-bioengineering bacteria. We found that the ROS level decreased by about 20–50% and the age-related lipofuscin accumulation was reduced by 15–25%. Moreover, the PT-feeding worms were more active at all life periods, and more resistant to acute stressors. Intriguingly, their lifespans were prolonged by ~21.7%. Comparative RNA-seq analysis indicated that many gene expressions were dramatically regulated by PT-diet, such as cysteine-rich protein (scl-11/12/13), sulfur-related enzyme (cpr-2), longevity gene (jnk-1) and stress response (sod-3/5, gps-5/6, gst-18/20, hsp-12.8). Both the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that neuroactivity pathways were upregulated, while phosphoryl transfer and DNA-repair pathways were down-regulated in good-appetite young worms. The findings pave the way for pro-longevity of multicellular organisms by PT-bacterial interference.

Panton Valentine leucocidin enhances community-acquired methicillin-resistant Staphylococcus aureus colonisation of the gut

ObjectiveCommunity-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) independently emerged and became epidemic at the end of the 20th century. Since gut carriage was reported for CA-MRSA and since the common feature of historical CA-MRSA is to harbour Panton Valentine leucocidin (PVL), the question of the possible involvement of this toxin in gut carriage was investigated in mice and cellular models.MethodsCA-MRSA of three lineages (USA300, USA1100, and ST80) and their isogenic Δpvl derivatives, were tested in competition for gut colonisation in mice and in a model of bacterial adhesion to mucus-producing intestinal epithelial cells.ResultsMice inoculated with CA-MRSA and their Δpvl derivatives had their gut successfully colonised by the three lineages regardless of the presence of PVL; however, the wild type (WT) CA-MRSA outcompeted the Δpvl derivatives by at least 3 log after 40 days for all lineages tested. In vitro competition of CA-MRSA with their Δpvl derivatives showed no fitness disequilibrium after 6 weeks, ensuring that the results obtained in mice did not result from direct bacterial interference. Direct fluorescence assay of mice intestine showed S. aureus localised at the mucosal surface of the intestine and within the intestinal crypts, but not within epithelial cells, suggesting a bacterial tropism for the mucus layer. Significant difference in adhesion to intestinal epithelial cells between WT and pvl knockout was only observed on mucus-producing cells, and not on non-producing ones.ConclusionPVL enhances CA-MRSA gut colonisation in mice by a mechanism involving adhesion-colonisation of the mucus layer.

Alternative treatment approaches of urinary tract infections caused by uropathogenic Escherichia coli strains

Urinary tract infections (UTIs) are the most widespread and annoying infections affecting millions of people every year annually. The biggest problems of urinary diseases are recurrences, increasing resistance of uropathogens to commonly used antibiotics, as well as the high health care costs of afflicted persons. Uropathogenic Escherichia coli strains (UPECs) are the most dominant etiologic agents of community-acquired infections of this type. During UTI pathogenesis, UPECs utilize various virulence factors, especially mono- and polyadhesive appendages of the chaperone-usher secretion pathway (CUP) required for adhesion, invasion and biofilm formation. Commonly used antibiotics for UTI treatment are usually effective, but their long-term utility may affect gut microbiota of the treated individuals and cause selection of drug resistant uropathogenic variants. Due to increasing resistance of UPEC strains to antibiotics via the evolution of specific defense mechanisms, there is a need to develop alternative methods and therapeutic strategies to fight UTIs (vaccines, receptor analogues, pilicides and curlicides, bacterial interference or phagotherapy). Such therapeutic approaches usually target processes enabling uropathogens to survive within the urinary tract and cause recurrent infections.

Biodegradation of the Allelopathic Chemical Pterostilbene by a Sphingobium sp. Strain from the Peanut Rhizosphere

ABSTRACT Many plants produce allelopathic chemicals, such as stilbenes, to inhibit pathogenic fungi. The degradation of allelopathic compounds by bacteria associated with the plants would limit their effectiveness, but little is known about the extent of biodegradation or the bacteria involved. Screening of tissues and rhizosphere of peanut (Arachis hypogaea) plants revealed substantial enrichment of bacteria able to grow on resveratrol and pterostilbene, the most common stilbenes produced by the plants. Investigation of the catabolic pathway in Sphingobium sp. strain JS1018, isolated from the rhizosphere, indicated that the initial cleavage of pterostilbene was catalyzed by a carotenoid cleavage oxygenase (CCO), which led to the transient accumulation of 4-hydroxybenzaldehyde and 3,5-dimethoxybenzaldehyde. 4-Hydroxybenzaldehyde was subsequently used for the growth of the isolate, while 3,5-dimethoxybenzaldehyde was further converted to a dead-end metabolite with a molecular weight of 414 (C24H31O6). The gene that encodes the initial oxygenase was identified in the genome of strain JS1018, and its function was confirmed by heterologous expression in Escherichia coli. This study reveals the biodegradation pathway of pterostilbene by plant-associated bacteria. The prevalence of such bacteria in the rhizosphere and plant tissues suggests a potential role of bacterial interference in plant allelopathy. IMPORTANCE Pterostilbene, an analog of resveratrol, is a stilbene allelochemical produced by plants to inhibit microbial infection. As a potent antioxidant, pterostilbene acts more effectively than resveratrol as an antifungal agent. Bacterial degradation of this plant natural product would affect the allelopathic efficacy and fate of pterostilbene and thus its ecological role. This study explores the isolation and abundance of bacteria that degrade resveratrol and pterostilbene in peanut tissues and rhizosphere, the catabolic pathway for pterostilbene, and the molecular basis for the initial cleavage of pterostilbene. If plant allelopathy is an important process in agriculture and management of invasive plants, the ecological role of bacteria that degrade the allelopathic chemicals must be equally important.