The role of the type-III secretion system of Gram-negative bacteria in the regulation of chronic infections

Zigangirova, N. A.; Nesterenko, L. N.; Tiganova, I. L.; Kost, Elena A.

doi:10.3103/s0891416812030081

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Therapeutic agents that target virulence determinants of pathogenic bacteria have become an increasingly promising alternative to antibiotics [ 20 , 21 ]. T3SS proteins are attractive targets for “anti-virulence” compounds because they are often essential to the virulence of widely distributed Gram-negative bacterial pathogens of plants, animals, and humans.…”

Section: Discussionmentioning

confidence: 99%

Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayPseudomonas aeruginosaInfection in Mice

Sheremet

Zigangirova

Zayakin

et al. 2018

BioMed Research International

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Pseudomonas aeruginosa is a cause of high mortality in burn, immunocompromised, and surgery patients. High incidence of antibiotic resistance in this pathogen makes the existent therapy inefficient. Type three secretion system (T3SS) is a leading virulence system of P. aeruginosa that actively suppresses host resistance and enhances the severity of infection. Innovative therapeutic strategies aiming at inhibition of type three secretion system of P. aeruginosa are highly attractive, as they may reduce the severity of clinical manifestations and improve antibacterial immune responses. They may also represent an attractive therapy for antibiotic-resistant bacteria. Recently our laboratory developed a new small molecule inhibitor belonging to a class 2,4-disubstituted-4H-[1,3, 4]-thiadiazine-5-ones, Fluorothiazinon (FT), that effectively suppressed T3SS in chlamydia and salmonella in vitro and in vivo. In this study, we evaluate the activity of FT towards antibiotic-resistant clinical isolates of P. aeruginosa expressing T3SS effectors ExoU and ExoS in an airway infection model. We found that FT reduced mortality and bacterial loads and decrease lung pathology and systemic inflammation. In addition, we show that FT inhibits the secretion of ExoT and ExoY, reduced bacteria cytotoxicity, and increased bacteria internalization in vitro. Overall, FT shows a strong potential as an antibacterial therapy of antibiotic-resistant P. aeruginosa infection.

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Section: Discussionmentioning

confidence: 99%

Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayPseudomonas aeruginosaInfection in Mice

Sheremet

Zigangirova

Zayakin

et al. 2018

BioMed Research International

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“…Salmonella releases various proteins into the surrounding medium under in vitro culture conditions. One of these proteins is SipC protein, which in conjunction with the type III secretion system, acts both as membrane anchored translocation and as a translocated effector protein in the host cell (Scherer et al, 2000;Srikanth et al, 2011;Zigangirova et al, 2012). The nucleotide sequence of this SipC gene is wellknown and also available at the gene database ( Figure. 1).…”

Section: Introductionmentioning

confidence: 99%

Development of a lateral flow assay for the detection of Salmonella based on antibodies against peptides of the effect or protein SipC of the type III secretion system of Salmonella spp.

Fahlandt¹,

Schulz²,

Meyer³

2015

JEBAS

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KEYWORDS Salmonella SipCEffectors protein translocation Immunoassay lateral flow assay ABSTRACTPresent study was the first promising steps in developing a diagnostic procedure for detecting a Salmonella infection or contamination. The areas of application are human medicine, veterinary medicine and various industrial sectors. The development was based on the finding that high antigen areas are formed in the effectors protein SipC. These areas are used to generate antibodies against the synthetically produced peptides from 15-17 amino acids. By using a non-competitive lateral flow assay (FLA) developed under laboratory conditions, a Salmonella contamination could be successfully detected by the SipC protein released into the culture medium.

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Investigation of Proteus vulgaris and Elizabethkingia meningoseptica invasion on muscle oxidative stress and autophagy in Chinese soft-shelled turtle (Pelodiscus sinensis)

Bao

Deng³

et al. 2021

Sci Rep

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Muscle is an important structural tissue in aquatic animals and it is susceptible to bacterial and fungal infection, which could affect flesh quality and health. In this study, Chinese soft-shelled turtles were artificially infected with two pathogens, Proteus vulgaris and Elizabethkingia meningoseptica and the effects on muscle nutritional characteristics, oxidative stress and autophagy were assayed. Upon infection, the muscle nutritional composition and muscle fiber structure were notably influenced. Meanwhile, the mRNA expression of Nrf2 was down-regulated and Keap1 up-regulated, thus resulting in a decrease in antioxidant capacity and oxidative stress. However, with N-acetylcysteine treatment, the level of oxidative stress was decreased, accompanied by significant increases in antioxidant enzyme activities and the mRNA levels of SOD, CAT, GSTCD, and GSTO1. Interestingly, there was a significant increase in autophagy in the muscle tissue after the pathogen infection, but this increase could be reduced by N-acetylcysteine treatment. Our findings suggest that muscle nutritional characteristics were dramatically changed after pathogen infection, and oxidative stress and autophagy were induced by pathogen infection. However, N-acetylcysteine treatment could compromise the process perhaps by decreasing the ROS level and regulating Nrf2-antioxidant signaling pathways.

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The role of the type-III secretion system of Gram-negative bacteria in the regulation of chronic infections

Cited by 3 publications

References 36 publications

Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayPseudomonas aeruginosaInfection in Mice

Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayPseudomonas aeruginosaInfection in Mice

Development of a lateral flow assay for the detection of Salmonella based on antibodies against peptides of the effect or protein SipC of the type III secretion system of Salmonella spp.

Investigation of Proteus vulgaris and Elizabethkingia meningoseptica invasion on muscle oxidative stress and autophagy in Chinese soft-shelled turtle (Pelodiscus sinensis)

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