Target intelligence / Profile preview

Mannitol-specific phosphotransferase system Enzyme II component (MtlA) (MtlA)

Target
MtlA
Molecular classification
Enzyme, Transporter, Phosphotransferase
01

Overview

The bacterial mannitol-specific phosphotransferase system (PTS) is a specialized multi-domain protein complex that mediates the coupled transport and phosphorylation of mannitol into the bacterial cell [UniProt, 2024]. It is primarily defined by the Enzyme II (EII) component, specifically MtlA, which integrates a membrane-bound IIC transporter domain with cytoplasmic IIA and IIB phosphoryl-transfer domains [PubMed, 2012]. This system utilizes a high-energy phosphate from phosphoenolpyruvate (PEP) to produce intracellular mannitol-6-phosphate, a key intermediate for glycolysis [Wikipedia, 2023]. In addition to its transport function, the mannitol PTS plays a critical role in signal transduction, particularly in carbon catabolite repression, which allows bacteria to prioritize carbon sources and regulate virulence factors [PubMed, 2004]. As the PTS is entirely absent in humans, it represents an attractive target for the development of novel antimicrobial agents that could provide high selectivity [PubMed, 2005]. Targeting this system with experimental inhibitors, such as mannitol analogs, can effectively starve the pathogen and disrupt its metabolic flexibility, offering a potential pathway to treat resistant bacterial infections.

Other names
Enzyme II mannitolMannitol-specific PTSMannitol permeaseEIIMtlBacterial mannitol-specific phosphotransferase system
02

Mechanism of action

Inhibition of mannitol uptake and phosphorylation, leading to carbon starvation and disruption of catabolite repression-mediated gene regulation [PubMed, 2005].

03

Biological functions

Carbohydrate transportProtein phosphorylationMetabolic regulationSignal transduction
04

Disease associations

Infection
05

Safety considerations

Bacterial resistance development via mtlA mutationsPotential lack of efficacy in environments with alternative carbon sourcesEnsuring selectivity against human glucose/polyol transporters [PubMed, 2012]
06

Interacting drugs

Experimental mannitol analogs

1 more in the full profile.

07

Biomarkers

Intracellular mannitol-6-phosphate concentrationmtlA mRNA expression levelsBacterial growth inhibition in mannitol-dependent conditions

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