Glutamate Decarboxylase-Mediated Nisin Resistance in
            <i>Listeria monocytogenes</i>

Begley, Máire; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

doi:10.1128/aem.00203-10

Cited by 47 publications

(49 citation statements)

References 25 publications

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“…No role for GadD3 in acid tolerance has been established, although a gadD3 insertion mutant has been shown to be defective for intracellular growth (11). Recently, the construction of a gadD3 deletion mutant has been reported by Begley et al (2). However, in this work it was demonstrated that unlike GadD1, GadD3 does not play a role in nisin resistance, but no role in acid resistance was investigated.…”

mentioning

confidence: 84%

Characterization of the Intracellular Glutamate Decarboxylase System: Analysis of Its Function, Transcription, and Role in the Acid Resistance of Various Strains of Listeria monocytogenes

Karatzas

Suur

O’Byrne

2012

Appl Environ Microbiol

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ABSTRACTThe glutamate decarboxylase (GAD) system is important for the acid resistance ofListeria monocytogenes. We previously showed that under acidic conditions, glutamate (Glt)/γ-aminobutyrate (GABA) antiport is impaired in minimal media but not in rich ones, like brain heart infusion. Here we demonstrate that this behavior is more complex and it is subject to strain and medium variation. Despite the impaired Glt/GABA antiport, cells accumulate intracellular GABA (GABAi) as a standard response against acid in any medium, and this occurs in all strains tested. Since these systems can occur independently of one another, we refer to them as the extracellular (GADe) and intracellular (GADi) systems. We show here that GADicontributes to acid resistance since in a ΔgadD1D2mutant, reduced GABAiaccumulation coincided with a 3.2-log-unit reduction in survival at pH 3.0 compared to that of wild-type strain LO28. Among 20 different strains, the GADisystem was found to remove 23.11% ± 18.87% of the protons removed by the overall GAD system. Furthermore, the GADisystem is activated at milder pH values (4.5 to 5.0) than the GADesystem (pH 4.0 to 4.5), suggesting that GADiis the more responsive of the two and the first line of defense against acid. Through functional genomics, we found a major role for GadD2 in the function of GADi, while that of GadD1 was minor. Furthermore, the transcription of thegadgenes in three common reference strains (10403S, LO28, and EGD-e) during an acid challenge correlated well with their relative acid sensitivity. No transcriptional upregulation of thegadT2D2operon, which is the most important component of the GAD system, was observed, whilegadD3transcription was the highest among allgadgenes in all strains. In this study, we present a revised model for the function of the GAD system and highlight the important role of GADiin the acid resistance ofL. monocytogenes.

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confidence: 84%

Characterization of the Intracellular Glutamate Decarboxylase System: Analysis of Its Function, Transcription, and Role in the Acid Resistance of Various Strains of Listeria monocytogenes

Karatzas

Suur

O’Byrne

2012

Appl Environ Microbiol

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“…gadT1 and gadT2 encode antiporters which import glutamate and export GABA. Deletion of gadD1 impairs the ability of a strain to tolerate exposure to both sublethal and lethal levels of nisin (200). It was discovered that the intracellular ATP levels were reduced in the ⌬gadD1 mutant, being only approximately 60% of those of the parent, suggesting that GadD1 contributes significantly to ATP pools and hence to tolerance of nisin (200).…”

Section: Gad Systemmentioning

confidence: 99%

Lantibiotic Resistance

Draper

Cotter

Hill

et al. 2015

Microbiol Mol Biol Rev

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135

129

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SUMMARY The dramatic rise in the incidence of antibiotic resistance demands that new therapeutic options will have to be developed. One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific. Such resistance mechanisms often arise due to altered gene regulation following detection of antimicrobials/cell wall damage by sensory proteins at the membrane. This facilitates alterations to the cell wall or changes in the composition of the membrane. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials. In rare cases, bacteria have been shown to possess specific antilantibiotic mechanisms. These are often species specific and include the nisin lytic protein nisinase and the phenomenon of immune mimicry.

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“…Assessing the extent of induced nisin resistance among multiple strains is important in light of previous studies demonstrating variation in innate nisin resistance linked to a genomic island that is variably present in ϳ50% of L. monocytogenes genomes (10). Our data indicate that while salt-induced nisin resistance does occur in all the strains tested, variation in the extent of the protective effect of salt does exist.…”

Section: Discussionmentioning

confidence: 56%

Nisin Resistance of Listeria monocytogenes Is Increased by Exposure to Salt Stress and Is Mediated via LiaR

Bergholz

Tang

Wiedmann

et al. 2013

Appl Environ Microbiol

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bGrowth of Listeria monocytogenes on refrigerated, ready-to-eat food is a significant food safety concern. Natural antimicrobials, such as nisin, can be used to control this pathogen on food, but little is known about how other food-related stresses may impact how the pathogen responds to these compounds. Prior work demonstrated that exposure of L. monocytogenes to salt stress at 7°C led to increased expression of genes involved in nisin resistance, including the response regulator liaR. We hypothesized that exposure to salt stress would increase subsequent resistance to nisin and that LiaR would contribute to increased nisin resistance. Isogenic deletion mutations in liaR were constructed in 7 strains of L. monocytogenes, and strains were exposed to 6% NaCl in brain heart infusion broth and then tested for resistance to nisin (2 mg/ml Nisaplin) at 7°C. For the wild-type strains, exposure to salt significantly increased subsequent nisin resistance (P < 0.0001) over innate levels of resistance. Compared to the salt-induced nisin resistance of wild-type strains, ⌬liaR strains were significantly more sensitive to nisin (P < 0.001), indicating that induction of LiaFSR led to cross-protection of L. monocytogenes against subsequent inactivation by nisin. Transcript levels of LiaR-regulated genes were induced by salt stress, and lmo1746 and telA were found to contribute to LiaR-mediated salt-induced nisin resistance. These data suggest that environmental stresses similar to those on foods can influence the resistance of L. monocytogenes to antimicrobials such as nisin, and potential cross-protective effects should be considered when selecting and applying control measures for this pathogen on ready-to-eat foods.

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Glutamate Decarboxylase-Mediated Nisin Resistance in Listeria monocytogenes

Cited by 47 publications

References 25 publications

Characterization of the Intracellular Glutamate Decarboxylase System: Analysis of Its Function, Transcription, and Role in the Acid Resistance of Various Strains of Listeria monocytogenes

Characterization of the Intracellular Glutamate Decarboxylase System: Analysis of Its Function, Transcription, and Role in the Acid Resistance of Various Strains of Listeria monocytogenes

Lantibiotic Resistance

Nisin Resistance of Listeria monocytogenes Is Increased by Exposure to Salt Stress and Is Mediated via LiaR

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