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Updated: Dec 28, 2025

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
Published on: January 5, 2024
Phylogenetic analysis reveals an ancient gene duplication as the origin of the MdtABC efflux pump
Kamil Górecki1, Megan M McEvoy1,2,3
1Institute for Society & Genetics, University of California, Los Angeles, California, United States of America.
Abstract:
The efflux pumps from the Resistance-Nodulation-Division family, RND, are main contributors to intrinsic antibiotic resistance in Gram-negative bacteria. Among this family, the MdtABC pump is unusual by having two inner membrane components. The two components, MdtB and MdtC are homologs, therefore it is evident that the two components arose by gene duplication. In this paper, we describe the results obtained from a phylogenetic analysis of the MdtBC pumps in the context of other RNDs. We show that the individual inner membrane components (MdtB and MdtC) are conserved throughout the Proteobacterial species and that their existence is a result of a single gene duplication. We argue that this gene duplication was an ancient event which occurred before the split of Proteobacteria into Alpha-, Beta- and Gamma- classes. Moreover, we find that the MdtABC pumps and the MexMN pump from Pseudomonas aeruginosa share a close common ancestor, suggesting the MexMN pump arose by another gene duplication event of the original Mdt ancestor. Taken together, these results shed light on the evolution of the RND efflux pumps and demonstrate the ancient origin of the Mdt pumps and suggest that the core bacterial efflux pump repertoires have been generally stable throughout the course of evolution.
Insights
The MdtABC efflux pump in Gram-negative bacteria evolved from a single gene duplication event early in Proteobacteria evolution. This ancient duplication event predates major bacterial class divergences, highlighting stable bacterial pump evolution.
Area of Science:
- Microbiology
- Evolutionary Biology
- Molecular Biology
Background:
- Resistance-Nodulation-Division (RND) efflux pumps are crucial for intrinsic antibiotic resistance in Gram-negative bacteria.
- The MdtABC pump is unique within the RND family due to its two homologous inner membrane components, MdtB and MdtC.
Purpose of the Study:
- To investigate the evolutionary origins and phylogenetic context of the MdtBC inner membrane components within the RND family.
- To determine the duplication event's timing and its implications for RND efflux pump evolution.
Main Methods:
- Phylogenetic analysis of MdtBC pumps.
- Comparative analysis with other RND efflux pumps across bacterial species.
Main Results:
- The MdtB and MdtC inner membrane components are conserved across Proteobacterial species, originating from a single gene duplication.
- This gene duplication event is ancient, occurring before the divergence of Alpha-, Beta-, and Gamma-Proteobacteria.
- The MdtABC and MexMN pumps share a common ancestor, suggesting MexMN also arose from a gene duplication event.
Conclusions:
- The MdtABC pump system has ancient evolutionary origins within the RND family.
- Gene duplication events have played a significant role in the diversification of RND efflux pumps.
- Core bacterial efflux pump repertoires appear evolutionarily stable.
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