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1.
Molecules ; 27(19)2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2066273

ABSTRACT

Lysozymes are hydrolytic enzymes characterized by their ability to cleave the ß-(1,4)-glycosidic bonds in peptidoglycan, a major structural component of the bacterial cell wall. This hydrolysis action compromises the integrity of the cell wall, causing the lysis of bacteria. For more than 80 years, its role of antibacterial defense in animals has been renowned, and it is also used as a preservative in foods and pharmaceuticals. In order to improve the antimicrobial efficacy of lysozyme, extensive research has been intended for its modifications. This manuscript reviews the natural antibiotic compound lysozyme with reference to its catalytic and non-catalytic mode of antibacterial action, lysozyme types, susceptibility and resistance of bacteria, modification of lysozyme molecules, and its applications in the food industry.


Subject(s)
Anti-Infective Agents , Muramidase , Animals , Anti-Bacterial Agents/pharmacology , Antiviral Agents , Bacteria/metabolism , Food Industry , Muramidase/chemistry , Peptidoglycan/metabolism , Pharmaceutical Preparations
2.
Int J Mol Sci ; 23(16)2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1987835

ABSTRACT

The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n = 146) and healthy individuals (n = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria. COVID-19 subjects exhibit significant dysbiosis (p = 0.001) of the plasma microbiome with increased abundance of Actinobacteria spp. (p = 0.0332), decreased abundance of Bacteroides spp. (p = 0.0003), and an increased Firmicutes:Bacteroidetes ratio (p = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (p = 0.0013) and the gut microbial antigens PGN (p < 0.0001) and LPS (p = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.


Subject(s)
Actinobacteria , COVID-19 , Gastrointestinal Microbiome , Microbiota , Actinobacteria/genetics , Bacteria/genetics , Dysbiosis/microbiology , Feces/microbiology , Firmicutes/genetics , Gastrointestinal Microbiome/genetics , Humans , Lipopolysaccharides , Peptidoglycan , RNA, Ribosomal, 16S/genetics , SARS-CoV-2
3.
ACS Chem Biol ; 17(5): 1184-1196, 2022 05 20.
Article in English | MEDLINE | ID: covidwho-1783934

ABSTRACT

Vaccine scaffolds and carrier proteins increase the immunogenicity of subunit vaccines. Here, we developed, characterized, and demonstrated the efficacy of a novel microparticle vaccine scaffold comprised of bacterial peptidoglycan (PGN), isolated as an entire sacculi. The PGN microparticles contain bio-orthogonal chemical handles allowing for site-specific attachment of immunogens. We first evaluated the purification, integrity, and immunogenicity of PGN microparticles derived from a variety of bacterial species. We then optimized PGN microparticle modification conditions; Staphylococcus aureus PGN microparticles containing azido-d-alanine yielded robust conjugation to immunogens. We then demonstrated that this vaccine scaffold elicits comparable immunostimulation to the conventional carrier protein, keyhole limpet hemocyanin (KLH). We further modified the S. aureus PGN microparticle to contain the SARS-CoV-2 receptor-binding domain (RBD)─this conjugate vaccine elicited neutralizing antibody titers comparable to those elicited by the KLH-conjugated RBD. Collectively, these findings suggest that chemically modified bacterial PGN microparticles are a conjugatable and biodegradable microparticle scaffold capable of eliciting a robust immune response toward an antigen of interest.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , Humans , Peptidoglycan , Staphylococcus aureus , Vaccines, Conjugate , Vaccines, Subunit
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