RETRACTED: ChpK and MazF of the toxin–antitoxin modules are involved in the virulence of Leptospira interrogans during infection

Komi, Komi Koukoura; Ge, Yubin; Xin, Xiao-yang; Ojcius, David M.; Sun, Dexter; Hu, Weilin; Zhao, Xin; Lin, Xiaojie; Yan, Jie

doi:10.1016/j.micinf.2014.10.010

Cited by 19 publications

(25 citation statements)

References 64 publications

(64 reference statements)

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“…Also, the RelBE TA system of Vibrio cholerae affects biofilm formation and intestinal colonization (Wang et al, 2015). Moreover, in both Leptospira interrogans and Rickettsia spp., type II TA mutants were affected in their induction of apoptosis in eukaryotic cells (Audoly et al, 2011; Komi et al, 2015). Thus, a growing body of evidence suggests that these emerging virulence factors display functional and regulatory roles in the expression of multiple virulence traits.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Profiling of Type II Toxin–Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967–HP0968 System

et al. 2016

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Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence of H. pylori in the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin–antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome of H. pylori 26695: HP0315–HP0316, HP0892–HP0893, and HP0894–HP0895. Here we characterized a heretofore undescribed type II TA system in H. pylori, HP0967–HP0968, which is encoded by the bicistronic operon hp0968–hp0967 and belongs to the Vap family. The predicted HP0967 protein is a toxin with ribonuclease activity whereas HP0968 is an antitoxin that binds to its own regulatory region. We found that all type II TA systems were expressed in H. pylori during early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, the hp0968–hp0967 pair was the most affected under these environmental conditions. Transcription of hp0968–hp0967 was strongly induced in a mature H. pylori biofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. The hp0968–hp0967 TA system was the most frequent among 317 H. pylori strains isolated from all over the world. This study is the first report on the transcription of type II TA genes in H. pylori under different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute a bona fide type II TA system in H. pylori, whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa.

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Section: Introductionmentioning

confidence: 99%

Transcriptional Profiling of Type II Toxin–Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967–HP0968 System

et al. 2016

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“…After blocking with 5% BSA-PBS and washing with PBS, the cells were incubated with 1:100 diluted rabbit anti- L . interrogans strain Lai-IgG made in our laboratory [29], and 1:500 diluted Alexa Fluor 594-conjugated goat anti-rabbit-IgG (Invitrogen, USA) for 1 h at room temperature, respectively, to stain intracellular leptospires. After washing with PBS again, the cells were incubated with 1 μg/mL DAPI (Invitrogen) for 15 min to stain the cell nucleus.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were incubated with 1:100 diluted rabbit anti- L . interrogans strain Lai-IgG made in our laboratory [29], rat anti-human or mouse LAMP-1-IgG (Abcam, UK) for overnight at 4°C. After washing with PBS, the cells were stained with 1:500 diluted Alexa Fluor594-conjugated goat anti-rabbit-IgG (Invitrogen) or Alexa Fluor488-conjugated goat anti-rat-IgG (Abcam) for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis

Ojcius

et al. 2017

PLoS ONE

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ObjectiveTo identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans.MethodsMajor infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry.ResultsPeripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver and kidneys of infected mice. Levels of macrophage- but not neutrophil-specific chemokines and VECAMs were significantly increased in the samples from infected mice and patients. All macrophages tested had a higher ability than neutrophils to phagocytose and kill leptospires. Higher ROS and NO levels and [Ca2+]i in the macrophages were involved in killing leptospires. Human macrophages displayed more phagolysosome formation and a stronger leptospire-killing ability to than mouse macrophages.ConclusionsMononuclear-macrophages but not neutrophils represent the main infiltrating and anti-leptospiral phagocytes during leptospirosis. A lower level of phagosome-lysosome fusion may be responsible for the lower Leptospira-killing ability of human macrophages.

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“…Two out of 7 genes encode type IV secretion system proteins. Since our data suggested that MazE-lp and the MazEF-lp complex represses the expression of these genes by binding to the promoter region of mazE-lp, it may be possible that MazE-lp and the MazEF-lp complex are important not only for the repression of their own expression, but also for the functional regulation of the type IV secretion system, which is involved in the pathogenicity of L. pneumophila [Komi et al, 2015]. It should be noted that the transcription activity of mazEFlp and icmR promoters from L. pneumophila was measured in the presence or absence of MazE-lp or MazEF-lp complex in E. coli.…”

Section: Discussionmentioning

confidence: 93%

“…Since 91.6% of ORFs contain AACU sequences, MazF-lp, a 4-base cutter, would cause cell dormancy and cell death. It has been indicated that the ChpK and MazF proteins in TA modules are involved in the virulence of Leptospira interrogans during infection [Komi et al, 2015]. It is possible that the cellular function of MazF is divided into two groups based on the length of their recognition sequence.…”

Section: Discussionmentioning

confidence: 99%

Identification of MazF Homologue in <b><i>Legionella pneumophila</i></b> Which Cleaves RNA at the AACU Sequence

et al. 2018

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MazF is a sequence-specific endoribonuclease that is widely conserved in bacteria and archaea. Here, we found an MazF homologue (MazF-lp; LPO-p0114) in Legionella pneumophila. The mazF-lp gene overlaps 14 base pairs with the upstream gene mazE-lp (MazE-lp; LPO-p0115). The induction of mazF-lp caused cell growth arrest, while mazE-lp co-induction recovered cell growth in Escherichia coli. In vivo and in vitro primer extension experiments showed that MazF-lp is a sequence-specific endoribonuclease cleaving RNA at AACU. The endoribonuclease activity of purified MazF-lp was inhibited by purified MazE-lp. We found that MazE-lp and the MazEF-lp complex specifically bind to the palindromic sequence present in the 5′-untranslated region of the mazEF-lp operon. MazE-lp and MazEF-lp both likely function as a repressor for the mazEF-lp operon and for other genes, including icmR, whose gene product functions as a secretion chaperone for the IcmQ pore-forming protein, by specifically binding to the palindromic sequence in 5′-UTR of these genes.

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RETRACTED: ChpK and MazF of the toxin–antitoxin modules are involved in the virulence of Leptospira interrogans during infection

Cited by 19 publications

References 64 publications

Transcriptional Profiling of Type II Toxin–Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967–HP0968 System

Transcriptional Profiling of Type II Toxin–Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967–HP0968 System

Mononuclear-macrophages but not neutrophils act as major infiltrating anti-leptospiral phagocytes during leptospirosis

Identification of MazF Homologue in <b><i>Legionella pneumophila</i></b> Which Cleaves RNA at the AACU Sequence

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