# FrlP, an ABC type I importer component of Bacillus subtilis: regulation and impact in bacterial fitness

**Authors:** Inês C. Gonçalves, Ana Pontes, Carla Gonçalves, Isabel de Sá-Nogueira

PMC · DOI: 10.1128/jb.00320-25 · 2025-10-30

## TL;DR

This study explores how Bacillus subtilis imports and uses fructosamines, revealing new insights into its transport mechanisms and fitness in ecological niches.

## Contribution

The study identifies FrlP and MsmX as key components for fructosamine uptake and highlights functional redundancy in ABC transporters.

## Key findings

- FrlONM and FrlP are essential for fructosevaline uptake in B. subtilis.
- MsmX can substitute for FrlP as an energy motor in the ABC importer.
- FrlP is specific to B. subtilis, suggesting its role in plant-associated fitness.

## Abstract

Bacillus subtilis is able to catabolize fructosamines, also known as Amadori rearrangement products. The frlBONMD-frlP operon mediates this process and is subjected to specific and global regulation. Although the degradation pathway favoring α-glycated amino acids is known, the mechanisms of substrate uptake have remained unclear. In this study, mutagenic and functional analyses revealed that FrlONM, a type I ABC importer, along with the nucleotide-binding domain (NBD) FrlP, is required for the uptake of fructosevaline. Transcriptional and translation frlP-lacZ fusions indicated that frlP is induced by fructosevaline and negatively regulated by the FrlR repressor. In addition, we show that MsmX, a multitask NBD of B. subtilis, is also able to serve as an energy motor of this type I ABC importer and that its presence alongside FrlP is vital for optimal growth on fructosevaline. To address the physiological significance of this functional redundancy, we assessed the distribution of ABC type I NBDs FrlP and MsmX across the Bacillaceae family. MsmX is homogeneously distributed in the Bacillaceae family tree, while FrlP is restricted to the Bacillus subtilis group, suggesting that the presence of FrlP together with other components of the fructosamines operon is important for bacterial fitness in plant-associated ecological niches.

Bacillus subtilis is widely applied in the industry as a microbial cell factory, as a biofertilizer for sustainable agriculture, in the animal feed industry and as human probiotic. In its natural environment, B. subtilis helps to shape the gut microbiome and the phytomicrobiome. Fructosamines, or Amadori rearrangement products, are ubiquitously found in nature and serve as precursors of toxic cell end-products implicated in the pathology of human diseases. This study provides a solid contribution to a deep knowledge of transport mechanisms, genetic regulation, and physiological relevance of fructosamines utilization in B. subtilis. Moreover, it highlights an unusual strategy to adapt to alterations in nutrient availability by swapping the energy providing domain of ABC transporters.

## Linked entities

- **Genes:** frlP (fructose-amino acid ABC transporter (ATP-binding subunit)) [NCBI Gene 937070], frlR (transcriptional regulator) [NCBI Gene 915920], msmX (multiple sugar (maltodextrins) transporter ATP-binding protein) [NCBI Gene 937422]
- **Proteins:** frlP (fructose-amino acid ABC transporter (ATP-binding subunit)), msmX (multiple sugar (maltodextrins) transporter ATP-binding protein)
- **Chemicals:** fructosevaline (PubChem CID 118222559)
- **Species:** Bacillus subtilis (taxon 1423)

## Full-text entities

- **Chemicals:** nucleotide (MESH:D009711), alpha-glycated amino acids (-), Fructosamines (MESH:D019270)
- **Species:** Bacillus subtilis subsp. subtilis (subspecies) [taxon 135461], Homo sapiens (human, species) [taxon 9606], Bacillus subtilis (species) [taxon 1423]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12632257/full.md

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Source: https://tomesphere.com/paper/PMC12632257