Multiple Toxin-Antitoxin Systems in Mycobacterium tuberculosis

Sala, Ambre; Bordes, Patricia; Genevaux, Pierre

doi:10.3390/toxins6031002

Cited by 233 publications

(245 citation statements)

References 99 publications

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“…Toxin-antitoxin systems are highly redundant. In Mycobacterium tuberculosis, more than 79 different toxinantitoxin systems have been identified [22]. We investigated one possible system, yoeB, in S aureus, but many others likely exist.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic-tolerant Staphylococcus aureus Biofilm Persists on Arthroplasty Materials

Urish

DeMuth

Kwan

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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Background The continued presence of biofilm may be one cause of the high risk of failure observed with irrigation and débridement with component retention in acute periprosthetic joint infection (PJI). There is a poor understanding of the role of biofilm antibiotic tolerance in PJI. Questions/purposes (1) Do increasing doses of cefazolin result in decreased viable biofilm mass on arthroplasty materials? (2) Is cefazolin resistance phenotypic or genotypic? (3) Is biofilm viability a function of biofilm depth after treatment with cefazolin? (4) Is the toxin-antitoxin system, yoeB expression, associated with antibiotic stress?Methods Methicillin-sensitive Staphylococcus aureus biofilm was cultured on total knee arthroplasty (TKA) materials and exposed to increasing doses of cefazolin (control, 0.5, 1.0, 10.0, 100.0 lg/mL). Quantitative confocal microscopy and quantitative culture were used to measure viable biofilm cell density. To determine if cefazolin resistance was phenotypic or genotypic, we measured minimum inhibitory concentration (MIC) after exposure to different cefazolin concentrations; changes in MIC would suggest genotypic features, whereas unchanged MIC would suggest phenotypic behavior. Finally, quantitative reverse transcription-polymerase chain reaction was used to quantify expression of yoeB levels between biofilm and planktonic bacteria after exposure to 1 lg/mL cefazolin for 3 hours. Results Although live biofilm mass was reduced by exposure to cefazolin when compared with biofilm mass in controls (39.2 9 10 3 ± 26.4 9 10 3 pixels), where the level after 0.5 lg/mL exposure also showed reduced mass (20.3 9 10 3 ± 11.9 9 10 3 pixels), no further reduction was seen after higher doses (mass at 1.0 lg/mL: 5.0 9 10 3 pixels ± 1.1 9 10 3 pixels; at 10.0 lg/mL: 6.4 9 10 3 ± 9.6 9 10 3 pixels; at 100.0 lg/mL: 6.4 9 10 3 ± 3.9 9 10 3 ). At the highest concentration tested (100 lg/ mL), residual viable biofilm was present on all three materials, and there were no differences in percent biofilm survival among cobalt-chromium (18.5% ± 15.1%),The project described was supported by the National Institutes of Health through Grant Number KL2 TR000146 (KLU 123Clin Orthop Relat Res (2016) 474:1649-1656 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® polymethylmethacrylate (22.8% ± 20.2%), and polyethylene (14.7% ± 10.4%). We found that tolerance was a phenotypic phenomenon, because increasing cefazolin exposure did not result in changes in MIC as compared with controls (MIC in controls: 0.13 ± 0.02; at 0.5 lg/mL: 0.13 ± 0.001, p = 0.96; at 1.0 lg/m: 0.14 ± 0.04, p = 0.95; at 10.0 lg/m: 0.11 ± 0.016, p = 0.47; at 100.0 lg/m: 0.94 ± 0.047, p = 0.47). Expression of yoeB after 1 lg/mL cefazolin for 3 hours in biofilm cells was greater in biofilm but not in planktonic cells (biofilm: 62.3-fold change, planktonic cells: À78.8-fold change, p \ 0.001). Conclusions Antibiotics are inadequate at complete removal of the biofilm from the surface o...

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Section: Discussionmentioning

confidence: 99%

Antibiotic-tolerant Staphylococcus aureus Biofilm Persists on Arthroplasty Materials

Urish

DeMuth

Kwan

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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“…In addition to transcriptional regulation, it is increasingly being recognized that post-translational regulation of gene expression is a key component of Mtb phase variation (27). Thus, several dozen toxins encoded by the Mtb genome contain the potential to target and degrade specific transcripts and are regulated by their cognate antitoxin pairs yet exhibit promiscuous binding affinities (35,36). Numerous small RNA molecules with the ability to disrupt gene expression have been identified (37).…”

Section: Discussionmentioning

confidence: 99%

The Mycobacterium tuberculosis Clp Gene Regulator Is Required for in Vitro Reactivation from Hypoxia-induced Dormancy

McGillivray

Golden

Kaushal

2015

Journal of Biological Chemistry

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“…Recent advances in genome sequencing and bioinformatics have revealed a high prevalence of toxin–antitoxin (TA) systems in prokaryotes, which has served as a starting point for diverse and intensive studies of TA systems [1,2,3,4,5]. Over the past decades, a large number of divergent structures and physiological functions of proteins from bacterial TA systems have been characterized.…”

Section: Biological Roles Of Ta Systemsmentioning

confidence: 99%

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

Lee

2016

Toxins

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Bacterial toxin–antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein–protein interactions. Accumulating knowledge about the structure–function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.

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Multiple Toxin-Antitoxin Systems in Mycobacterium tuberculosis

Cited by 233 publications

References 99 publications

Antibiotic-tolerant Staphylococcus aureus Biofilm Persists on Arthroplasty Materials

Antibiotic-tolerant Staphylococcus aureus Biofilm Persists on Arthroplasty Materials

The Mycobacterium tuberculosis Clp Gene Regulator Is Required for in Vitro Reactivation from Hypoxia-induced Dormancy

Structure, Biology, and Therapeutic Application of Toxin–Antitoxin Systems in Pathogenic Bacteria

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