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ncbi / amr

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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Problems identifying MCR-9 genes #127

Closed HilaryESR closed 1 year ago

HilaryESR commented 1 year ago

We have noticed an issue with AMRfinder not identifying MCR 9 genes present in our isolates. For example, the isolate SRR21865985 contains MCR 9.2 - it is a full length copy of the gene and a 100% match to the MCR 9.2 gene in the AMRfinder database. However AMRfinder does not return this gene when we run it on either the assembly or a file of the proteins. Would you be able to look into this for us, as it seems like a bug?

I have attached an assembly file for this isolate (SRR21865985.fasta.gz) and an alignment of the MCR gene from this isolate with the 3 MCR 9 genes in the AMRfinder database.

We've also observed this problem in many other isolates which we know from PCR and abricate have MCR 9, but it is never detected by AMRfinder. The other MCR genes seem to be detected OK. We are using AMRfinder 3.11.4.

SRR21865985.fasta.gz

MCR9_alignment.fasta.gz

vbrover commented 1 year ago

Yes! There are two levels of "AMRness": "core" and "plus". The mcr-9 family is "plus", i.e., it is not that resistant as the "core" families. By default, amrfinder reports only core families. Please use the --plus option.

HilaryESR commented 1 year ago

Ah thanks for clarifying that! I had assumed that as the rest of the MCR genes seem to be in core, that MCR-9 would be as well. At least that is an easy fix!

evolarjun commented 1 year ago

Hi @HilaryESR,

Just to clarify why our curators recategorized MCR-9 from "core" to "plus". After we added mcr to the database and identified mcr-9 in a number of US isolates in NCBI Pathogen Detection. Our colleagues from NARMS became alarmed and tested isolates with mcr-9 for colistin resistance. They found that mcr-9 did not confer resistance to colistin:

We tested over 100 Salmonella enterica and Escherichia coli isolates with mcr-9 from the National Antimicrobial Resistance Monitoring System (NARMS) in the United States for their susceptibility to colistin and found that every isolate was susceptible, with an MIC of ≤1 μg/ml.

From the abstract of Tyson et al. 2020

vbrover commented 1 year ago

See also https://www.ncbi.nlm.nih.gov/pathogens/refgene/#mcr-9.