Haematological, biochemical and immunological biomarkers, antibacterial activity, and survival in Nile tilapia Oreochromis niloticus after treatment using antimicrobial peptide LL-37 against Streptococcus agalactiae

Sousa, Elielma Lima de; Assane, Inácio Mateus; Santos-Filho, Norival A.; Cilli, Eduardo Maffud; Jesus, Raphael Barbetta de; Pilarski, Fabiana

doi:10.1016/j.aquaculture.2020.736181

Cited by 15 publications

(8 citation statements)

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“…As the first defensive line for an organism’s immune system against the threat of antibiotic-resistant strains, − antimicrobial peptides (AMPs) have a broad antibacterial spectrum, fast bactericidal rate, and a lower likelihood of resistance development, which make them a favorable alternative to antibiotics. Protegrin-1 (PG-1) is a pig-derived AMP with four cysteine residues stabilized by two disulfide bonds (Figure D).…”

Section: Introductionmentioning

confidence: 99%

PEGylation of the Antimicrobial Peptide PG-1: A Link between Propensity for Nanostructuring and Capacity of the Antitrypsin Hydrolytic Ability

Wang

et al. 2021

J. Med. Chem.

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The increasing prevalence of antibacterial resistance globally underscores the urgent need for updated antimicrobial peptides (AMPs). Here, we describe a strategy for inducing the self-assembly of protegrin-1 (PG-1) into nanostructured antimicrobial agents with significantly improved pharmacological properties. Our strategy involves PEGylation in the terminals of PG-1 and subsequent self-assembly in aqueous media in the absence of exogenous excipients. Compared with the parent PG-1, the therapeutic index (TI) of NPG 750 (TI Gram-negative bacteria = 17.07) and CPG 2000 (TI All = 26.02) was increased. Importantly, NPG 750 and CPG 2000 offered higher stability toward trypsin degradation. Mechanistically, NPG 750 and CPG 2000 exerted their bactericidal activity by membrane-active mechanisms due to which microbes were not prone to develop resistance. Our findings proved PEGylation as a simple yet versatile strategy for generating AMP-derived bioactive drugs with excellent antitrypsin hydrolytic ability and lower cytotoxicity. This provides a theoretical basis for the further clinical application of AMPs.

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Section: Introductionmentioning

confidence: 99%

PEGylation of the Antimicrobial Peptide PG-1: A Link between Propensity for Nanostructuring and Capacity of the Antitrypsin Hydrolytic Ability

Wang

et al. 2021

J. Med. Chem.

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“…Based on these aspects and the results from our previous studies (de Sousa et al . 2021), LL‐37 in vivo toxicity against the Nile tilapia can be expected to be negligible.…”

Section: Discussionmentioning

confidence: 99%

“…2020; de Sousa et al . 2021). HDPs are short polypeptide sequences (~12–50 residues) produced by all living organisms as a host defence mechanism against infection (Yeaman and Yount 2003; Haney et al .…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity and antimicrobial activity of synthetic peptides alone or in combination with conventional antimicrobials against fish pathogenic bacteria

et al. 2021

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Aims This study aimed to evaluate the in vitro cytotoxicity and efficacy of synthetic host defence peptides (HDPs), alone or in combination with florfenicol (FFC), oxytetracycline (OTC) or thiamphenicol (TAP), against different pathogenic bacteria isolated from diseased fish. Methods and Results Solid‐phase synthesis, purification and characterization of several HDPs were performed manually, using the fluorenylmethyloxycarbonyl protecting group in different resins and via high‐performance liquid chromatography‐mass spectrometry, respectively. The in vitro cytotoxicity and antimicrobial activity of HDPs, FFC, OTC and TAP against Nile tilapia red blood cells (RBCs) and relevant fish pathogenic bacteria (Aeromonas, Citrobacter, Edwardsiella, Streptococcus, Lactococcus and Vibrio) was determined using the haemolysis assay and broth microdilution method, respectively. The checkerboard assay was used to evaluate the synergy between the most active HDPs and other antimicrobials against the tested strains. MUC 7 12‐mer, FFC, OTC and TAP were not cytotoxic to Nile tilapia RBCs, in all tested concentrations. LL‐37, (p‐BthTX‐I)2 and Hylin‐a1 were not cytotoxic at concentrations up to 78·13, 19·53 and 9·77 μg ml−1, respectively. HDPs demonstrated potent antimicrobial activity (minimum inhibitory concentration ≤31·25 µg ml−1) against Aeromonas jandaei (KR‐12‐a5), Citrobacter freundii (Kr‐12‐a5; (p‐BthTX‐I)2; LL‐37; and Hylin a1), Streptococcus agalactiae (Hylin a1; (p‐BthTX‐I)2 and LL‐37), Lactococcus garviae (Hylin a1), and Vibrio fluvialis (KR‐12‐a5). The combinations of (p‐BthTX‐I)2 with TAP and LL‐37 with FFC showed synergistic activity against C. freundii (fractional inhibitory concentration index of 0·25 and 0·50, respectively). Conclusions Synthetic HDPs have the potential as a good treatment option for bacterial diseases in aquaculture. Significance and Impact of the Study The in vivo effectiveness of synthetic HDPs such as KR‐12‐a5; LL‐37; (p‐BthTX‐I)2 and Hylin a1 can be tested alone or in combination with conventional antimicrobials as a treatment option to reduce the use of antimicrobials in aquaculture.

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“…Typical symptoms of the Streptococcus -infected tilapia include blackening of the fish surface, prominent or turbid eyeballs, whiteness, bleeding, abdominal spots, and bleeding on the inner side of the lid ( Perera et al, 1994 ). Previous research studies on tilapia infected by S. agalactiae and S. iniae focused mainly on the isolation, identification and typing of strains, screening of drugs for the prevention and treatment of Streptococcus -infected tilapia, the drug resistance, and vaccine development ( Suanyuk et al, 2008 ; Cai et al, 2020 ; De Sousa et al, 2021 ). Most research studies on the immune mechanism of tilapia mainly focused on the kidney and spleen ( Zhu et al, 2015 ; Zhu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative Transcriptomic Analysis Reveals the Regulated Expression Profiles in Oreochromis niloticus in Response to Coinfection of Streptococcus agalactiae and Streptococcus iniae

et al. 2022

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Tilapia (Oreochromis sp.) is one of the important economical fishes in the world. Streptococcosis is commonly found in tilapia, causing severe and devastating effects in tilapia cultures. Streptococcus agalactiae and Streptococcus iniae are the predominant pathogens causing tilapia streptococcosis. To understand the molecular mechanisms underlying differential streptococcal infection patterns, Nile tilapias (Oreochromis niloticus) were infected by 1 × 107 CFU/mL S. agalactiae, 1 × 107 CFU/mL S. iniae, and 1 × 107 CFU/mL S. agalactiae and S. iniae (1:1), respectively, and transcriptome analysis was conducted to the intestine samples of Nile tilapia (Oreochromis niloticus) at 6, 12, 24 h, and 7 days post-infection. A total of 6,185 genes that differentially expressed among groups were identified. Eight differentially expressed genes (DEGs) including E3 ubiquitin-protein ligase TRIM39-like, C-X-C motif chemokine 10-like(CXCL 10), C-C motif chemokine 19-like, interleukin-1 beta-like, IgM heavy chain VH region, partial, IgG Fc-binding protein, proteasome subunit beta type-8 (PSMB8), and ATP synthase F(0) complex subunit B1, mitochondrial that involved in the immune system were selected, and their expression levels in the coinfection group were significantly higher than those in either of the single infection groups. These genes were associated with four different KEGG pathways. Additionally, the differential expression of eight DEGs was validated by using the RT-qPCR approach, and their immunological importance was discussed. The results provided insights into the responses of tilapia against S. agalactiae and S. iniae at the transcriptome level, promoting our better understanding of immune responses for aquatic animal against Streptococcus.

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Haematological, biochemical and immunological biomarkers, antibacterial activity, and survival in Nile tilapia Oreochromis niloticus after treatment using antimicrobial peptide LL-37 against Streptococcus agalactiae

Cited by 15 publications

References 58 publications

PEGylation of the Antimicrobial Peptide PG-1: A Link between Propensity for Nanostructuring and Capacity of the Antitrypsin Hydrolytic Ability

PEGylation of the Antimicrobial Peptide PG-1: A Link between Propensity for Nanostructuring and Capacity of the Antitrypsin Hydrolytic Ability

Cytotoxicity and antimicrobial activity of synthetic peptides alone or in combination with conventional antimicrobials against fish pathogenic bacteria

Comparative Transcriptomic Analysis Reveals the Regulated Expression Profiles in Oreochromis niloticus in Response to Coinfection of Streptococcus agalactiae and Streptococcus iniae

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