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1.
Elife ; 92020 12 08.
Article in English | MEDLINE | ID: mdl-33287959

ABSTRACT

Under eubiotic conditions commensal microbes are known to provide a competitive barrier against invading bacterial pathogens in the intestinal tract, on the skin or on the vaginal mucosa. Here, we evaluate the role of lung microbiota in Pneumococcus colonization of the lungs. In eubiosis, the lungs of mice were dominantly colonized by Lactobacillus murinus. Differential analysis of 16S rRNA gene sequencing or L. murinus-specific qPCR of DNA from total organ homogenates vs.broncho alveolar lavages implicated tight association of these bacteria with the host tissue. Pure L. murinus conditioned culture medium inhibited growth and reduced the extension of pneumococcal chains. Growth inhibition in vitro was likely dependent on L. murinus-produced lactic acid, since pH neutralization of the conditioned medium aborted the antibacterial effect. Finally, we demonstrate that L. murinus provides a barrier against pneumococcal colonization in a respiratory dysbiosis model after an influenza A virus infection, when added therapeutically.


Subject(s)
Lactobacillus/metabolism , Lung/microbiology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/physiology , Animals , Carrier State , Culture Media, Conditioned , Female , Lactic Acid/metabolism , Lactic Acid/pharmacology , Mice , Mice, Inbred C57BL , Symbiosis
3.
Nat Biotechnol ; 38(5): 600-608, 2020 05.
Article in English | MEDLINE | ID: mdl-32066956

ABSTRACT

The western corn rootworm (WCR) decimates maize crops worldwide. One potential way to control this pest is treatment with entomopathogenic nematodes (EPNs) that harbor bacterial symbionts that are pathogenic to insects. However, WCR larvae sequester benzoxazinoid secondary metabolites that are produced by maize and use them to increase their resistance to the nematodes and their symbionts. Here we report that experimental evolution and selection for bacterial symbionts that are resistant to benzoxazinoids improve the ability of a nematode-symbiont pair to kill WCR larvae. We isolated five Photorhabdus symbionts from different nematodes and increased their benzoxazinoid resistance through experimental evolution. Benzoxazinoid resistance evolved through multiple mechanisms, including a mutation in the aquaporin-like channel gene aqpZ. We reintroduced benzoxazinoid-resistant Photorhabdus strains into their original EPN hosts and identified one nematode-symbiont pair that was able to kill benzoxazinoid-sequestering WCR larvae more efficiently. Our results suggest that modification of bacterial symbionts might provide a generalizable strategy to improve biocontrol of agricultural pests.


Subject(s)
Aquaporins/genetics , Benzoxazines/pharmacology , Drug Resistance, Bacterial , Nematoda/microbiology , Photorhabdus/physiology , Zea mays/growth & development , Animals , Bacterial Proteins/genetics , Evolution, Molecular , Genetic Engineering , Mutation , Nematoda/pathogenicity , Pest Control, Biological , Photorhabdus/drug effects , Photorhabdus/genetics , Plant Diseases/prevention & control , Zea mays/parasitology
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