NMR Hydrophilic Metabolomic Analysis of Bacterial Resistance Pathways Using Multivalent Antimicrobials with Challenged and Unchallenged Wild Type and Mutated Gram-Positive Bacteria

Autor:	Michelle L. Aries, Mary J. Cloninger
Rok vydání:	2021
Předmět:	antibiotic resistance Magnetic Resonance Spectroscopy QH301-705.5 membrane disruption Article Catalysis dendrimers Inorganic Chemistry Bacillus cereus Drug Resistance Bacterial Humans Biology (General) quaternary ammonium compounds Physical and Theoretical Chemistry QD1-999 Molecular Biology Gram-Positive Bacterial Infections Spectroscopy DABCO metabolomics nuclear magnetic resonance Gram-positive bacteria Organic Chemistry General Medicine Anti-Bacterial Agents Computer Science Applications Chemistry Mutation Metabolome Metabolic Networks and Pathways
Zdroj:	International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 22; Issue 24; Pages: 13606 International Journal of Molecular Sciences, Vol 22, Iss 13606, p 13606 (2021)
ISSN:	1422-0067
DOI:	10.3390/ijms222413606
Popis:	Multivalent membrane disruptors are a relatively new antimicrobial scaffold that are difficult for bacteria to develop resistance to and can act on both Gram-positive and Gram-negative bacteria. Proton Nuclear Magnetic Resonance (1H NMR) metabolomics is an important method for studying resistance development in bacteria, since this is both a quantitative and qualitative method to study and identify phenotypes by changes in metabolic pathways. In this project, the metabolic differences between wild type Bacillus cereus (B. cereus) samples and B. cereus that was mutated through 33 growth cycles in a nonlethal dose of a multivalent antimicrobial agent were identified. For additional comparison, samples for analysis of the wild type and mutated strains of B. cereus were prepared in both challenged and unchallenged conditions. A C16-DABCO (1,4-diazabicyclo-2,2,2-octane) and mannose functionalized poly(amidoamine) dendrimer (DABCOMD) were used as the multivalent quaternary ammonium antimicrobial for this hydrophilic metabolic analysis. Overall, the study reported here indicates that B. cereus likely change their peptidoglycan layer to protect themselves from the highly positively charged DABCOMD. This membrane fortification most likely leads to the slow growth curve of the mutated, and especially the challenged mutant samples. The association of these sample types with metabolites associated with energy expenditure is attributed to the increased energy required for the membrane fortifications to occur as well as to the decreased diffusion of nutrients across the mutated membrane.
Databáze:	OpenAIRE
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