Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic

Ferraboschi, Patrizia; Ciceri, Samuele; Grisenti, Paride

doi:10.3390/antibiotics10121534

Cited by 178 publications

(125 citation statements)

References 336 publications

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“…Thus, this may explain why lysozyme can more easily hydrolyze the wall of S. epidermidis 444 in comparison to L. rhamnosus GG. Moreover, several previous studies have demonstrated the ability of lysozyme to prevent biofilm formation (Leitch and Willcox 1999 ; Ferraboschi and Ciceri 2021 ). Hence, a concentration of 30 μg/mL was able to decrease the biofilm-forming capacities of a wide spectrum of hospital and reference strains of microorganisms such as Gardnerella vaginalis , Staphylococcus aureus , Staphylococcus epidermidis and Pseudomonas aeruginosa (Hukić et al 2018 ).…”

Section: Discussionmentioning

confidence: 97%

“…The obtained results were in accordance with other studies revealing that L. rhamnosus GG and S. epidermidis 444 can survive in a harsh environment. Thus, they can resist pH values as low as 2.5 but with a low survival rate and poor proliferative capacity (Nishiyama et al 2016 ; Ferraboschi and Ciceri 2021 ). Therefore, this may justify the decrease in the survival rate in the stomach.…”

Section: Discussionmentioning

confidence: 99%

“…When adding lysozyme and EDTA to oxytetracycline hydrochloride, an MBC was achieved as shown previously. Thus, bacterial cell wall lyses may be behind this increased inhibition that is possibly due to a better antibiotic access to the targeted cells(Ferraboschi and Ciceri 2021 ). Therefore, a synergistic effect took place where the antibiotic was able to better attack the proteins after a cell wall disruption by lysozyme.…”

Section: Discussionmentioning

confidence: 99%

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Lactobacillus rhamnosus and Staphylococcus epidermidis in gut microbiota: in vitro antimicrobial resistance

et al. 2022

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The gastrointestinal tract is one of the most complex microbiological niches containing beneficial and non-pathogenic bacterial strains of which some may evolve into virulent under specific conditions. Lactobacillus rhamnosus GG is of the most known beneficial species with an ability to protect the intestine as opposed to Staphylococcus epidermidis 444 which causes serious health risks due to its high antimicrobial resistance. This study investigates first the survival and coexistence ability of L. rhamnosus GG, and S. epidermidis 444 at different pH levels. Subsequently, lysozyme's antimicrobial and antibiofilm effect on these two strains was elucidated before adding different concentrations of oxytetracycline hydrochloride antibiotic. Results showed that 50% inhibition of L. rhamnosus GG, S. epidermidis 444, and a co-culture of these planktonic strains were obtained respectively at a lysozyme concentration of 30, 18, and 26 mg/mL after the addition of ethylenediamine tetra-acetic acid (EDTA). At a pH of 7.5, mixing lysozyme (at IC50) and EDTA with oxytetracycline hydrochloride (700 μg/mL) showed an additional bactericidal effect as compared to its known bacteriostatic effect. Similarly, the addition of lysozyme to the antibiotic further increased the biofilm eradication of S. epidermidis 444 and L. rhamnosus GG where a maximal eradication of 70% was reached. Therefore, the potential development of new drugs based on adding a lysozyme-EDTA mixture to different types of antibiotics may be highly promising.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lactobacillus rhamnosus and Staphylococcus epidermidis in gut microbiota: in vitro antimicrobial resistance

et al. 2022

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“…HEWL is a potential alternative to antibiotics: however, it is difficult to express in microbial expression systems in large quantity, which greatly limits its application [ 29 ]. To date, heterologous expression of HEWL has been attempted in microbial expression systems, but low expression levels are still a problem and an issue to be solved.…”

Section: Discussionmentioning

confidence: 99%

Recombinant expression of hen egg white lysozyme with the assistance of xylanase fusion partner inPichia pastoris

et al. 2022

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Due to its bacteriolytic activity, hen egg white lysozyme (HEWL) is widely used in the feed, food, and pharmaceutical industries. However, its application is hindered by low protein expression levels in microbial expression systems. In this work, a novel fusion protein expression strategy was proposed for increasing the expression level of HEWL. First, HEWL, fused with a highly expressed fusion protein partner xylanase XynCDBFV, is expressed in Pichia pastoris . Secondly, a linker including endogenous protease cleavage sites was introduced between two fusion proteins in order to separate them directly during the secretion process. Finally, the results show that the supernatant of XynCDBFV-HEWL has a higher HEWL expression level and activity compared with HEWL only. It should be noted that the expression of HEWL reaches to about 3.5 g/L, and the activity of HEWL against Micrococcus lysodeikticus reaches to 1.50 × 10 5 U/mL in a fed-batch fermentation, which is currently the highest level of recombinant expression of an egg white-derived lysozyme. Taken together, we acquired bioactive HEWL for large-scale recombinant production in Pichia pastor is using a novel fusion protein expression strategy, which could then be used for a variety of applications.

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“…OLFM4 is then involved in the destruction of the intestine. Clinical research is focusing on the role of LYZ as a potential biomarker in feces and blood of intestinal inflammatory diseases [ 33 ] and its medical application, using the protein’s anti-inflammatory, anti-bacterial and immunomodulating effects in gastroenterological diseases [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Increased expression of OLFM4 and lysozyme during necrotizing enterocolitis in neonates: an observational research study

et al. 2022

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Background In neonatal patients with necrotizing enterocolitis (NEC) the inflammatory response is mediated by a plurality of different proteins. The proteins olfactomedin 4 (OLFM4) and lysozyme (LYZ) are part of the intestinal mucosal defense and especially OLFM4 has rarely been evaluated in neonatal gastrointestinal diseases. The aim of this study was to analyze whether expression levels of both proteins of innate immunity, OLFM4 and lysozyme, were increased during NEC in neonates. Methods Intestinal tissues of patients with NEC were examined with immunohistochemical staining of formalin-fixed and paraffin-embedded sections of resected tissue using antibodies against OLFM4 and lysozyme. Staining-positive tissues were semi-quantitatively scored from 0 (no staining), 1 (weak staining), 2 (moderate staining) to 3 (highly intense staining) by two individual investigators. Intestinal tissue of infants with volvulus was used as a control as other intestinal tissue without major inflammation was not available. Results Both applied antibodies against OLFM4 showed different staining patterns with higher staining intensity of the antibody OLFM4 (D1E4M). OLFM4 (median score of the antibody OLFM4 (D1E4M): 3.0) and lysozyme (median score: 3.0) are highly expressed in intestinal and immune cells during NEC. Expression of OLFM4 and lysozyme in the control samples with volvulus was observable but significantly lower (median score of the antibody OLFM4 (D1E4M): 1.25; median score of the antibody against LYZ: 2.0; p = 0.033 and p = 0.037, respectively). Conclusions Both proteins, OLFM4 and lysozyme, may play a role in the pathogenesis of NEC in neonatal patients, but the exact mechanisms of OLFM4 and lysozyme function and their role in immunological responses have not yet been resolved in detail. These observations add new insights as basis for further large-scale population research.

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Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic

Cited by 178 publications

References 336 publications

Lactobacillus rhamnosus and Staphylococcus epidermidis in gut microbiota: in vitro antimicrobial resistance

Lactobacillus rhamnosus and Staphylococcus epidermidis in gut microbiota: in vitro antimicrobial resistance

Recombinant expression of hen egg white lysozyme with the assistance of xylanase fusion partner inPichia pastoris

Increased expression of OLFM4 and lysozyme during necrotizing enterocolitis in neonates: an observational research study

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