Large-Scale Comparison of Toxin and Antitoxins in Listeria monocytogenes

Agüero, J.A; Akarsu, Hatice; Aguilar-Bultet, Lisandra; Oevermann, Anna; Falquet, Laurent

doi:10.3390/toxins12010029

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…None of the TA modules has been experimentally analyzed so far, although a few studies have been performed on chromosomally encoded TAs of L. monocytogenes strains [ 31 , 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

Plasmidome of Listeria spp.—The repA-Family Business

Chmielowska

Korsak

Chapkauskaitse

et al. 2021

IJMS

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Bacteria of the genus Listeria (phylum Firmicutes) include both human and animal pathogens, as well as saprophytic strains. A common component of Listeria spp. genomes are plasmids, i.e., extrachromosomal replicons that contribute to gene flux in bacteria. This study provides an in-depth insight into the structure, diversity and evolution of plasmids occurring in Listeria strains inhabiting various environments under different anthropogenic pressures. Apart from the components of the conserved plasmid backbone (providing replication, stable maintenance and conjugational transfer functions), these replicons contain numerous adaptive genes possibly involved in: (i) resistance to antibiotics, heavy metals, metalloids and sanitizers, and (ii) responses to heat, oxidative, acid and high salinity stressors. Their genomes are also enriched by numerous transposable elements, which have influenced the plasmid architecture. The plasmidome of Listeria is dominated by a group of related replicons encoding the RepA replication initiation protein. Detailed comparative analyses provide valuable data on the level of conservation of these replicons and their role in shaping the structure of the Listeria pangenome, as well as their relationship to plasmids of other genera of Firmicutes, which demonstrates the range and direction of flow of genetic information in this important group of bacteria.

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“…None of the TA modules has been experimentally analyzed so far, although a few studies have been performed on chromosomally encoded TAs of L. monocytogenes strains [ 31 , 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

Plasmidome of Listeria spp.—The repA-Family Business

Chmielowska

Korsak

Chapkauskaitse

et al. 2021

IJMS

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“…Only a few studies on TASs of L. monocytogenes have been conducted so far and those were also limited to few strains and few TAS pairs [ 42 , 43 ]. The strain ATCC19117 was studied using in silico approach where few TASs pair were found (lmo0887-0888, lmo0113-0114, and Imo1301-1302) with subsequent 3D structure and possible inhibitory peptide analysis [ 44 ]. As an endoribonuclease, the toxin PemK selectively identifies and cut the tetrad sequence UAUU in a target mRNA without the need for ribosomes.…”

Section: Discussionmentioning

confidence: 99%

“…In CASTp analysis, one largest pocket was found as active sites with SA surface area of 74.975 and volume of 24.651 amino acids. The majority of viruses with toxin-antitoxin in their system pose a significant threat to individual’s health [ 44 ]. Although tremendous progress has been made in investigating the roles of toxin-antitoxins in recent years, many functional and structural aspects of toxin-antitoxins and their effectors remain elusive.…”

Section: Discussionmentioning

confidence: 99%

In silico annotation of a hypothetical protein from Listeria monocytogenes EGD-e unfolds a toxin protein of the type II secretion system

Tasneem¹,

Gupta²,

Momin³

et al. 2023

Genomics Inform

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The gram-positive bacterium Listeria monocytogenes is an important foodborne intracellular pathogen that is widespread in the environment. The functions of hypothetical proteins (HP) from various pathogenic bacteria have been successfully annotated using a variety of bioinformatics strategies. In this study, a HP Imo0888 (NP_464414.1) from the Listeria monocytogenes EGD-e strain was annotated using several bioinformatics tools. Various techniques, including CELLO, PSORTb, and SOSUIGramN, identified the candidate protein as cytoplasmic. Domain and motif analysis revealed that the target protein is a PemK/MazF-like toxin protein of the type II toxin-antitoxin system (TA) which was consistent with BLASTp analysis. Through secondary structure analysis, we found the random coil to be the most frequent. The Alpha Fold 2 Protein Structure Prediction Database was used to determine the three-dimensional (3D) structure of the HP using the template structure of a type II TA PemK/MazF family toxin protein (DB ID_AFDB: A0A4B9HQB9) with 99.1% sequence identity. Various quality evaluation tools, such as PROCHECK, ERRAT, Verify 3D, and QMEAN were used to validate the 3D structure. Following the YASARA energy minimization method, the target protein's 3D structure became more stable. The active site of the developed 3D structure was determined by the CASTp server. Most pathogens that harbor TA systems create a crucial risk to human health. Our aim to annotate the HP Imo088 found in Listeria could offer a chance to understand bacterial pathogenicity and identify a number of potential targets for drug development.

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“…Moreover, the "guilt-by-association" strategy used throughout the annotation process, i.e., targeting loci directly neighboring orphan toxin or antitoxin genes, facilitated the discovery of new TA protein families. In the case of Listeria monocytogenes, TASmania-assisted large-scale genomic comparisons led to the identification of 14 putative TA genes [51].…”

Section: Type II Ta Systems In Pathogenic Bacteriamentioning

confidence: 99%

Targeting Type II Toxin–Antitoxin Systems as Antibacterial Strategies

Równicki

Lasek

Trylska

et al. 2020

Toxins

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The identification of novel targets for antimicrobial agents is crucial for combating infectious diseases caused by evolving bacterial pathogens. Components of bacterial toxin–antitoxin (TA) systems have been recognized as promising therapeutic targets. These widespread genetic modules are usually composed of two genes that encode a toxic protein targeting an essential cellular process and an antitoxin that counteracts the activity of the toxin. Uncontrolled toxin expression may elicit a bactericidal effect, so they may be considered “intracellular molecular bombs” that can lead to elimination of their host cells. Based on the molecular nature of antitoxins and their mode of interaction with toxins, TA systems have been classified into six groups. The most prevalent are type II TA systems. Due to their ubiquity among clinical isolates of pathogenic bacteria and the essential processes targeted, they are promising candidates for the development of novel antimicrobial strategies. In this review, we describe the distribution of type II TA systems in clinically relevant human pathogens, examine how these systems could be developed as the targets for novel antibacterials, and discuss possible undesirable effects of such therapeutic intervention, such as the induction of persister cells, biofilm formation and toxicity to eukaryotic cells.

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Large-Scale Comparison of Toxin and Antitoxins in Listeria monocytogenes

Cited by 4 publications

References 38 publications

Plasmidome of Listeria spp.—The repA-Family Business

Plasmidome of Listeria spp.—The repA-Family Business

In silico annotation of a hypothetical protein from Listeria monocytogenes EGD-e unfolds a toxin protein of the type II secretion system

Targeting Type II Toxin–Antitoxin Systems as Antibacterial Strategies

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