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In depth phosphoproteomeic analysis reveal the underlying signaling of antibiotic resistance

ABSTRACT: Antimicrobial resistance is widespread across the globe. Here we presented a dynamic view of protein phosphoregulations during resistance development. Specific phosphorylation motifs and highly conserved phosphorylated residues on transcription factors were identified involving in regulating resistance for the first time implying the extent of phosphorylation regulation is far more important than we thought. Much effort need to be done in understanding the contribution of each signaling pathway to the development of resistance. Therefore, the dataset presented here could be a valuable resource for future works to decipher signaling mechanisms involved in AMR.

ORGANISM(S): Escherichia Coli

SUBMITTER: Simone Lemeer

PROVIDER: PXD008947 | JPOST Repository | Thu Feb 23 00:00:00 GMT 2023

REPOSITORIES: jPOST

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			Action	DRS
	20170419_OR13_MH_W3110_0129_blk_1.raw	Raw
	20170419_OR13_MH_W3110_0129_blk_2.raw	Raw
	20170419_OR13_MH_W3110_0129_blk_3.raw	Raw
	20170419_OR13_MH_W3110_0129_cipro_1.raw	Raw
	20170419_OR13_MH_W3110_0129_cipro_2.raw	Raw

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Project description:<p>The study of antimicrobial resistance (AMR) in infectious diarrhea has generally been limited to cultivation, antimicrobial susceptibility testing and targeted PCR assays. When individual strains of significance are identified, whole genome shotgun (WGS) sequencing of important clones and clades is performed. Genes that encode resistance to antibiotics have been detected in environmental, insect, human and animal metagenomes and are known as "resistomes". While metagenomic datasets have been mined to characterize the healthy human gut resistome in the Human Microbiome Project and MetaHIT and in a Yanomani Amerindian cohort, directed metagenomic sequencing has not been used to examine the epidemiology of AMR. Especially in developing countries where sanitation is poor, diarrhea and enteric pathogens likely serve to disseminate antibiotic resistance elements of clinical significance. Unregulated use of antibiotics further exacerbates the problem by selection for acquisition of resistance. This is exemplified by recent reports of multiple antibiotic resistance in Shigella strains in India, in Escherichia coli in India and Pakistan, and in nontyphoidal Salmonella (NTS) in South-East Asia. We propose to use deep metagenomic sequencing and genome level assembly to study the epidemiology of AMR in stools of children suffering from diarrhea. Here the epidemiology component will be surveillance and analysis of the microbial composition (to the bacterial species/strain level where possible) and its constituent antimicrobial resistance genetic elements (such as plasmids, integrons, transposons and other mobile genetic elements, or MGEs) in samples from a cohort where diarrhea is prevalent and antibiotic exposure is endemic. The goal will be to assess whether consortia of specific mobile antimicrobial resistance elements associate with species/strains and whether their presence is enhanced or amplified in diarrheal microbiomes and in the presence of antibiotic exposure. This work could potentially identify clonal complexes of organisms and MGEs with enhanced resistance and the potential to transfer this resistance to other enteric pathogens.</p> <p>We have performed WGS, metagenomic assembly and gene/protein mapping to examine and characterize the types of AMR genes and transfer elements (transposons, integrons, bacteriophage, plasmids) and their distribution in bacterial species and strains assembled from DNA isolated from diarrheal and non-diarrheal stools. The samples were acquired from a cohort of pediatric patients and controls from Colombia, South America where antibiotic use is prevalent. As a control, the distribution and abundance of AMR genes can be compared to published studies where resistome gene lists from healthy cohort sequences were compiled. Our approach is more epidemiologic in nature, as we plan to identify and catalogue antimicrobial elements on MGEs capable of spread through a local population and further we will, where possible, link mobile antimicrobial resistance elements with specific strains within the population.</p>

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In depth phosphoproteomeic analysis reveal the underlying signaling of antibiotic resistance

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