Deletion of major shell proteins of ethanolamine utilization microcompartment reduces intrinsic antibiotic resistance, biofilm, and intracellular survival of Salmonella Typhimurium.
Minal R Bhalerao, Aishwarya S Davkhar, Ajit R Sawant, Anindya S Ghosh, Tiffany N Harris, Thomas A Bobik, Ankita Saha, Sachin B Agawane, Chiranjit Chowdhury
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引用次数: 0
Abstract
With the high rise in Salmonella infections and emergence of antibiotic resistance, developing a novel strategy to control the pathogen is imperative. Earlier studies have revealed that ethanolamine (EA) metabolism plays a crucial role in Salmonella intestinal colonization; however, the potential of this metabolism as a therapeutic target remains unexplored. The EA metabolic enzymes are localized within a proteinaceous microcompartment (MCP) shell composed of thousands of copies of shell proteins encoded by five genes from the eut operon. Our study reveals that supplementation of EA and vitamin B12 in both rich and minimal media enhances biofilm formation, motility, and tolerance to antibiotics. Conversely, mutants deficient in EA metabolism due to defective MCP shell exhibited no physiological fitness. Fascinatingly, these mutants exhibited enhanced susceptibility to various antibiotics and lower expression of biofilm and curli. Also, a mutation in one of the major shell proteins reduced intramacrophage viability of Salmonella. Notably, phenotypes were restored upon ectopic expression of corresponding genes. Mutations in the MCP shell proteins downregulated the expression of genes related to pathogenicity. Overall, this study sheds new light on understanding the relationship between EA metabolism and bacterial physiology that would pave the way for developing novel therapeutic interventions against Salmonella.
期刊介绍：
Research in Microbiology is the direct descendant of the original Pasteur periodical entitled Annales de l''Institut Pasteur, created in 1887 by Emile Duclaux under the patronage of Louis Pasteur. The Editorial Committee included Chamberland, Grancher, Nocard, Roux and Straus, and the first issue began with Louis Pasteur''s "Lettre sur la Rage" which clearly defines the spirit of the journal:"You have informed me, my dear Duclaux, that you intend to start a monthly collection of articles entitled "Annales de l''Institut Pasteur". You will be rendering a service that will be appreciated by the ever increasing number of young scientists who are attracted to microbiological studies. In your Annales, our laboratory research will of course occupy a central position, but the work from outside groups that you intend to publish will be a source of competitive stimulation for all of us."That first volume included 53 articles as well as critical reviews and book reviews. From that time on, the Annales appeared regularly every month, without interruption, even during the two world wars. Although the journal has undergone many changes over the past 100 years (in the title, the format, the language) reflecting the evolution in scientific publishing, it has consistently maintained the Pasteur tradition by publishing original reports on all aspects of microbiology.
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