Toxin-Antitoxin Systems Alter Adaptation of Mycobacterium smegmatis to Environmental Stress

Zhang, Lan-Yue; Wang, Chunliang; Yan, Mei-Yi; Geng, Yiman; Yin, Han; Jia, Hepeng; Zhu, Chuanzhi; Li, Zihui; Ren, Ge; Pan, Liping; Sun, Yicheng; Zhang, Zong-De

doi:10.1128/spectrum.02815-22

Cited by 7 publications

(7 citation statements)

References 45 publications

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“…M. smegmatis, a nonpathogenic bacterium, is the perfect model to study the varied pathogenicity of Mtb. 14 The bacterial membrane of M. smegmatis is rich in lipidic components that are very similar to those found in Mtb. 15 The protective effect of the liposome formations produced from lipids extracted from the bacterial membrane of M. smegmatis in a murine model of progressive pulmonary tuberculosis is well documented.…”

Section: Introductionmentioning

confidence: 86%

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Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria

Pu,

Wang,

Wang

et al. 2024

Mol. Pharmaceutics

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Tuberculosis (TB) is a chronic disease caused byMycobacterium tuberculosis (Mtb), which shows a long treatment cycle often leads to drug resistance, making treatment more difficult. Immunogens present in the pathogen’s cell membrane can stimulate endogenous immune responses. Therefore, an effective lipid-based vaccine or drug delivery vehicle formulated from the pathogen’s cell membrane can improve treatment outcomes. Herein, we extracted and characterized lipids fromMycobacterium smegmatis, and the extracts contained lipids belonging to numerous lipid classes and compounds typically found associated with mycobacteria. The extracted lipids were used to formulate biomimetic lipid reconstituted nanoparticles (LrNs) and LrNs-coated poly(lactic-co-glycolic acid) nanoparticles (PLGA-LrNs). Physiochemical characterization and results of morphology suggested that PLGA-LrNs exhibited enhanced stability compared with LrNs. And both of these two types of nanoparticles inhibited the growth of M. smegmatis. After loading different drugs, PLGA-LrNs containing berberine or coptisine strongly and synergistically prevented the growth of M. smegmatis. Altogether, the bacterial membrane lipids we extracted with antibacterial activity can be used as nanocarrier coating for synergistic antibacterial treatment of M. smegmatisan alternative model of Mtb, which is expected as a novel therapeutic system for TB treatment.

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Section: Introductionmentioning

confidence: 86%

“…M. smegmatis, a nonpathogenic bacterium, is the perfect model to study the varied pathogenicity of Mtb . The bacterial membrane of M.…”

Section: Introductionmentioning

confidence: 99%

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria

Pu,

Wang,

Wang

et al. 2024

Mol. Pharmaceutics

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“…The toxin-antitoxin (TA) systems were required to adapt to the environmental stresses rapidly 56 , stabilize the integron 57 , or form the persisted cell 58 . Toxin gene BJA_RS08285 involved in TA system was significantly up-regulated in dSH3_IP mutant bacteroid in symbiosis.…”

Section: Symbiotic Incompatibility Between Dsh3_ip Mutant Bacteroid A...mentioning

confidence: 99%

A novel intergenic dSH3-irr insertion mutation in Bradyrhizobium diazoefficiens causes its symbiotic incompatibility with soybean

jin

liu

et al. 2023

Preprint

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Legumes and rhizobia collaborate to fix nitrogen in the host plant nodules, but some inadvertent mutation may generate unexpected symbiosis. We reported an altered host range symbiosis of Bradyrhizobium diazoefficiens USDA110 mutant dSH3_IP when associating with Sophora flavescens. Recently, we found SH3_IP cannot symbiose with original host soybean (Glycine max), and mutant influenced iron response regulator, which forms convergent gene pair with dSH3 in strain USDA110. The reason of symbiotic mismatching between soybean and dSH3_IP was explored through dual RNA-seq transcriptome and symbiotic characterization. We discovered dSH3_IP bacteroid assimilated more nutrition, triggered stronger immune responses and perturbed the symbiotic components in soybean nodules. Anyway, the incompatible symbiosis between dSH3_IP and soybean originated from intergenic insertion of dSH3-irr, which importance was not uncovered previously and may be used as a potential regulatory element in the future to regulate the SNF efficiency by artificial genetic design.

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“…2 The function of them is controversial and enigmatic, which arranged from genome stability, nutritional stress, biofilm and persister formation in antibiotic tolerance, oxidative stress to phage defense. [3][4][5] Based on the properties and action mode of antitoxins, the toxin-antitoxin system could be divided into eight groups. 2 Among them, Type II is the most common and most studied, with both toxins and their cognate antitoxins being proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Toxin–antitoxin systems have also been found in chromosomes, which are believed to have been acquired via horizontal gene transfer 2 . The function of them is controversial and enigmatic, which arranged from genome stability, nutritional stress, biofilm and persister formation in antibiotic tolerance, oxidative stress to phage defense 3–5 . Based on the properties and action mode of antitoxins, the toxin–antitoxin system could be divided into eight groups 2 .…”

Section: Introductionmentioning

confidence: 99%

Helicobacter macacaeMazF interplays with Escherichia coli homologs and enhances antibiotic tolerance

Zeng

et al. 2023

Helicobacter

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BackgroundToxin‐antitoxin systems are highly variable, even among strains of the same bacterial species. The MazEF toxin‐antitoxin system is found in many bacteria and plays important roles in various biological processes such as antibiotic tolerance and phage defense. However, no interplay of MazEF systems between different species was reported.Materials and MethodsMazEF toxin‐antitoxin system of Helicobacter macacae was examined in three Escherichia coli strains with and without endogenous MazEF knockout. In vivo toxicity, antibiotic tolerance, and live/dead staining followed by flowcytometry analysis were performed to evaluate the functionality and interplay of the toxin‐antitoxin system between the two species.ResultsControlled ectopic expression of MazF of H. macacae (MazFhm) in E. coli did not affect its growth. However, in endogenous MazEF knockout E. coli strains, MazFhm expression caused a sharp growth arrest. The toxicity of MazFhm could be neutralized by both the antitoxin of MazE homolog of H.macacae and the antitoxin of MazE of E. coli, indicating interplay of MazEF toxin‐antitoxin systems between the two species. Induced expression of MazFhm enhanced tolerance to a lethal dose of levofloxacin, suggesting enhanced persister formation, which was further confirmed by live/dead cell staining.ConclusionsThe MazEF toxin‐antitoxin system of H. macace enhances persister formation and thus antibiotic tolerance in E. coli. Our findings reveal an interplay between the MazEF systems of H. macacae and E. coli, emphasizing the need to consider this interaction while evaluating the toxicity and functionality of MazF homologs from different species in future studies.

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Toxin-Antitoxin Systems Alter Adaptation of Mycobacterium smegmatis to Environmental Stress

Cited by 7 publications

References 45 publications

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria

Lipids Extracted from Mycobacterial Membrane and Enveloped PLGA Nanoparticles for Encapsulating Antibacterial Drugs Elicit Synergistic Antimicrobial Response against Mycobacteria

A novel intergenic dSH3-irr insertion mutation in Bradyrhizobium diazoefficiens causes its symbiotic incompatibility with soybean

Helicobacter macacaeMazF interplays with Escherichia coli homologs and enhances antibiotic tolerance

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