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AMRFinderPlus - Identify AMR genes and point mutations, and virulence and stress resistance genes in assembled bacterial nucleotide and protein sequence.
https://www.ncbi.nlm.nih.gov/pathogens/antimicrobial-resistance/AMRFinder/
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Literature reference for aac(6')-Ib3 #128

Closed kalilamali closed 1 year ago

kalilamali commented 1 year ago
Hi, Could I get the reference to the literature used for: Gene symbol Subclass
aac(6')-Ib3 AMIKACIN/KANAMYCIN/TROBAMYCIN

The reference from the nucleotide acc (https://www.liebertpub.com/doi/10.1089/10766290260469516) states intermedium amikacin resistance but on this other paper the gene contribution seems limited: "Deleting acc (6′)-Ib3 had a more marked effect, increasing tobramycin and gentamicin sensitivity by 64- and 16-fold, respectively, and lowering the MICs below clinical resistance breakpoints while having no effect on amikacin resistance." https://www.mdpi.com/2079-6382/11/7/884 Thanks in advance, Karen.

vbrover commented 1 year ago

All genes are in the "Reference Gene Catalog": https://www.ncbi.nlm.nih.gov/pathogens/refgene/#aac(6')-Ib3 Add the column "Pubmed reference". It will point to https://pubmed.ncbi.nlm.nih.gov/9579076/.

evolarjun commented 1 year ago

Hi Karen,

Our primary aminoglycoside curator is on vacation right now, but for many of the genes you can get to the references used to fill out the phenotype information from our Reference Gene Catalog. You may have to click the "Choose columns" button and add the "Pubmed reference" column to the display to see it. In this case the reference PMID for the curation of WP_032488579.1 (aac(6')-Ib3) is 9579076

Thanks for your question, and I'll ping our curator when he gets back.

Arjun

feldgard commented 1 year ago

Looking at the MDPI paper (the knockout experiment paper), it appears they misidentified the resistance gene. The strain in which they knock out the aac(6')-Ib gene is "1260990", which according to Supplemental Table 1, we have assembled here: https://www.ncbi.nlm.nih.gov/pathogens//isolates/#SAMN15663259

This has an aac(6')-Ib4 gene, which does not confer amikacin resistance; positions 118 and 119 (sensu https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656343/) are QS, not QL (QL confers amikacin resistance; QS confers gentamicin resistance*). When I run this assembly through ResFinder, which is what the authors used, the closest hit in nucleotide space is aac(6')-Ib3, but the closest hit in protein space, which is what AMRFinderPlus uses, is aac(6')-Ib4 (and -Ib4 has the correct QS motif). So they do get the predicted result: knocking out a gentamicin resistance gene lowers the MIC of gentamicin, but not amikacin. Thanks for your question and my apologies for the delayed response.

Mike

*see: table 2 https://pubmed.ncbi.nlm.nih.gov/23730301/

kalilamali commented 1 year ago

Thank you so much for the very detailed and insightful answer!