Clinicians are currently observing the global emergence of plasmid-mediated resistance genes. A recent study identified the presence of mcr-9 colistin resistance in a canine urinary tract infection in Portugal. The causative agent, Enterobacter hormaechei, carried the gene on an IncHI2 plasmid. This discovery is particularly concerning because the strain remained phenotypically susceptible to colistin during testing. Such findings highlight a "silent" dissemination of resistance genes that standard laboratory tests might overlook.

Genetic Architecture of the mcr-9 Variant

The researchers utilized whole-genome sequencing to map the IncHI2 plasmid. Consequently, they identified a highly conserved genetic region involved in metal homeostasis and copper tolerance. This region includes the rcnR-rcnA-pcoE-ISSgsp1-pcoS-IS903-mcr-9-wbuC operon. Furthermore, the structural similarity of this plasmid to human-sourced sequences suggests a high potential for cross-species transmission. Because these plasmids are mobile, they facilitate the spread of multidrug resistance across various environments.

Why mcr-9 colistin resistance Remains Silent

Phenotypic resistance to colistin often depends on specific regulatory triggers. In this Portuguese strain, the absence of qseC and qseB regulatory genes likely explains the colistin-susceptible phenotype. Additionally, these two genes are essential for the activation and expression of the mcr-9 gene. Therefore, the bacteria carry the genetic potential for resistance without exhibiting it under standard conditions. However, the gene can become active if it transfers to a host that possesses the necessary regulatory machinery.

One Health and Genomic Surveillance

This case reinforces the critical need for a One Health approach to antimicrobial resistance (AMR). Since companion animals can harbor silent resistance genes, they may serve as unrecognized reservoirs for human infection. Moreover, genomic surveillance must go beyond phenotypic testing to capture the true prevalence of mobile resistance. Specifically, in India, where the AMR burden is high, implementing such rigorous monitoring is vital for preserving the efficacy of last-resort antibiotics like colistin.

Frequently Asked Questions

What is the clinical significance of mcr-9 colistin resistance?

While mcr-9 often appears silent, it represents a major public health threat. It is a mobile gene that can transfer between different bacterial species. If the gene moves into a host with the right regulatory genes, it can cause high-level colistin resistance, complicating the treatment of multidrug-resistant infections.

How does silent carriage impact antibiotic stewardship?

Silent carriage means that standard antimicrobial susceptibility testing may not detect the resistance potential of a strain. This can lead to the undetected spread of resistance genes within hospitals and communities. Consequently, clinicians must rely on genomic surveillance to identify these hidden threats and tailor infection control measures.

Is mcr-9 colistin resistance common in companion animals?

Recent studies suggest that mcr-9 is increasingly detected in companion animals, including dogs. This underscores the potential for zoonotic transmission of resistance genes. Therefore, a One Health framework that includes veterinary monitoring is essential to combat the global rise of antimicrobial resistance.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice and is not intended to replace professional judgment. Refer to the latest local and national guidelines for clinical practice.

References

Menezes J et al. Silent carriage of mcr-9 on IncHI2 plasmid in an Enterobacter hormaechei strain causing a urinary tract infection in a dog from Portugal. Vet Microbiol. 2026 Jun 01. doi: undefined. PMID: 42224776.

Kieffer N et al. A novel plasmid-encoded resistance gene, mcr-9, that confers inducible colistin resistance in Enterobacteriaceae. mBio. 2019;10(3):e00965-19. doi: 10.1128/mBio.00965-19.

Carroll LM et al. Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate. mBio. 2019;10(3):e00853-19. doi: 10.1128/mBio.00853-19.