Differential expression of antimicrobial peptides in corneal infection and regulation of antimicrobial peptides and reactive oxygen species by type III secretion system of Pseudomonas aeruginosa

Sharma, Prerana; Guha, Sanjukta; Garg, Prashant; Roy, Sanhita

doi:10.1093/femspd/fty001

Cited by 18 publications

(29 citation statements)

References 54 publications

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“…Genes among the Clinical Isolates of P. aeruginosa P. aeruginosa has a repertoire of toxins secreted by different secretory pathways. T3SS is one of the major virulence factors that have been shown to subvert host immune responses, including reactive oxygen species generation, in human corneal epithelial cells [42,43]. In this study, we screened thirty four ocular clinical isolates causing corneal infections and determined the presence of genes associated with virulence such as the main T3SS effector genes, exoS, exoT, exoU and exoY, as well as pscU and pscT, responsible for T3SS machinery [44].…”

Section: Differential Expression Of T3ssmentioning

confidence: 99%

Characterization of Ocular Clinical Isolates of Pseudomonas aeruginosa from Non-Contact Lens Related Keratitis Patients from South India

et al. 2020

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P. aeruginosa is the most common Gram-negative organism causing bacterial keratitis. Pseudomonas utilizes various virulence mechanisms to adhere and colonize in the host tissue. In the present study, we examined virulence factors associated with thirty-four clinical P. aeruginosa isolates collected from keratitis patients seeking care at L V Prasad Eye Institute, Hyderabad. The virulence-associated genes in all the isolates were genotyped and characteristics such as antibiotic susceptibility, biofilm formation, swarming motility, pyoverdine production and cell cytotoxicity were analyzed. All the isolates showed the presence of genes related to biofilm formation, alkaline proteases and elastases; however, there was a difference in the presence of genes related to the type III secretion system (T3SS). A higher prevalence of exoU+ genotype was noted in the drug-resistant isolates. All the isolates were capable of forming biofilms and more than 70% of the isolates showed good swarming motility. Pyoverdine production was not associated with the T3SS genotype. In the cytotoxicity assay, the presence of exoS, exoU or both resulted in higher cytotoxicity compared to the absence of both the genes. Overall, our results suggest that the T3SS profile is a good indicator of P. aeruginosa virulence characteristics and the isolates lacking the effector genes may have evolved alternate mechanisms of colonization in the host.

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Section: Differential Expression Of T3ssmentioning

confidence: 99%

Characterization of Ocular Clinical Isolates of Pseudomonas aeruginosa from Non-Contact Lens Related Keratitis Patients from South India

et al. 2020

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“…In our earlier study we investigated the expression of AMPs from corneal scrapings of patients with P. aeruginosa corneal infections and saw differential expression of several AMPs, including human β defensins (hBD) 2, and 3, S100A9, S100A12 and LL-37. We also found that PAO1 subverts the expression of these AMPs in HCECs in vitro [ 6 ]. However, we observed that the expression of the AMPs increased significantly when cells were exposed to PAO1Δ pscC , a T3SS mutant that fails to transfer exotoxins to the host cells.…”

Section: Resultsmentioning

confidence: 99%

“…In the cornea, P. aeruginosa activates the Toll like receptors (TLRs) that results in prompt production of cytokines and chemokines, recruitment of immune cells to the cornea and development of corneal opacity [ 2 ]. The corneal epithelium provides the first line of defense against invading bacteria [ 3 ] and the host immune response to P. aeruginosa is regulated by TLR4-MD-2 and TLR5 leading to an elevated expression of proinflammatory cytokines and antimicrobial peptides (AMPs) [ 2 , 4 – 6 ]. One of the fundamental virulence factors of P. aeruginosa is the type III secretion system (T3SS) which consists of a syringe-like apparatus that functions in a highly controlled manner to transport bacterial toxins and other proteins into the host cells [ 7 ] and amend different functions of the host to survive [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…One of the fundamental virulence factors of P. aeruginosa is the type III secretion system (T3SS) which consists of a syringe-like apparatus that functions in a highly controlled manner to transport bacterial toxins and other proteins into the host cells [ 7 ] and amend different functions of the host to survive [ 8 ]. We and others have recently shown that wild-type PAO1 subverts the host immune responses including AMP expression [ 6 ] and attenuates generation of reactive oxygen species (ROS) in neutrophils and epithelial cells by its T3SS [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis

2020

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Pseudomonas aeruginosa is an opportunistic pathogen and a major cause of corneal infections worldwide. The bacterium secretes several toxins through its type III secretion system (T3SS) to subvert host immune responses. In addition, it is armed with intrinsic as well as acquired antibiotic resistance mechanisms that make treatment a significant challenge and new therapeutic interventions are needed. Type III secretion inhibitors have been studied as an alternative or in accompaniment to traditional antibiotics to inhibit virulence of bacteria. In this study, INP0341, a T3SS inhibitor, inhibited cytotoxicity by P. aeruginosa toward human corneal epithelial cells (HCEC) at 100 μM without affecting bacterial growth in the liquid media. An increased expression of antimicrobial peptides and reactive oxygen species generation was also observed in cells exposed to P. aeruginosa in the presence of INP0341. Furthermore, INP0341 efficiently attenuated corneal infection by P. aeruginosa in an experimental model of murine keratitis as evident from corneal opacity, clinical score and bacterial load. Thus, INP0341 appears to be a promising candidate to treat corneal infection caused by P. aeruginosa and can be further considered as an alternative therapeutic intervention.

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“…There is a T3SS in P. aeruginosa, shared with many other Gram-negative bacteria, which transfer effector toxins directly from the bacterium into the host cell cytosol [11]. P. aeruginosa can repress AMP expression in both epithelial cells and macrophages by its T3SS in vitro [12]. ExsA is an essential transcriptional activator of T3SS in P. aeruginosa.…”

mentioning

confidence: 99%

Effects of human β-defensin 3 fused with carbohydrate-binding domain on the function of type III secretion system in Pseudomonas aeruginosa PA14

Liu

Dong

et al. 2020

Braz J Microbiol

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Antimicrobial peptides are considered to be one of the candidate antimicrobial agents for antibiotic-resistant bacterial infection in the future. The effects of antimicrobial peptide hBD3-CBD on Pseudomonas aeruginosa PA14 and PA14 ΔexsA were analyzed by the bactericidal effects, hemolysis assays, pyocyanin pigment productions, and virulence factor expressions (exoU, exoS, hcnA, and lasB). Pyocyanin production and virulence factor expressions are important features of the type III secretion system in Pseudomonas aeruginosa. HBD3-CBD killed PA14 and PA14 ΔexsA with similar efficiency; it lowered the hemolysis levels of PA14 and PA14 ΔexsA and reduced the pyocyanin production, biofilm formation, and exoU, exoS, and lasB expressions in PA14. Compared with PA14, PA14 ΔexsA showed a lower hemolysis effect, pyocyanin production, exoU, and lasB expressions. The effects of hBD3-CBD on the PA14 toxin secretion were similar to the changes in the type III secretion system mutant isolate PA14 ΔexsA. Our results demonstrated that the type III secretion system was involved in the biological functions on PA 14 from hBD3-CBD. Keywords Antimicrobial peptide. hBD3. Pseudomonas aeruginosa. T3SS Antimicrobial peptides (AMPs) are polypeptides with broadspectrum antimicrobial activity against bacteria, fungi, and other microorganisms [1]. Their potent activity at low concentrations against many pathogenic organisms, including multiresistant strains, makes AMPs attractive candidates as antimicrobial agents to many inflammatory and infectious diseases [2]. Human beta-defensin-3 (hBD3) is a multifunctional peptide and widely expressed in oral and other tissues. The antiinfective effects of this polypeptide have been confirmed by several studies [3-5].

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Differential expression of antimicrobial peptides in corneal infection and regulation of antimicrobial peptides and reactive oxygen species by type III secretion system of Pseudomonas aeruginosa

Cited by 18 publications

References 54 publications

Characterization of Ocular Clinical Isolates of Pseudomonas aeruginosa from Non-Contact Lens Related Keratitis Patients from South India

Characterization of Ocular Clinical Isolates of Pseudomonas aeruginosa from Non-Contact Lens Related Keratitis Patients from South India

Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis

Effects of human β-defensin 3 fused with carbohydrate-binding domain on the function of type III secretion system in Pseudomonas aeruginosa PA14

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