Bacteriology of Ophthalmic Infections
K. Balamurugan, U. Prithika in Pocket Guide to Bacterial Infections, 2019
Bacteriophage therapy, antibody therapy targeting the virulence factors of Staphylococcus, will be the effective alternates to antibiotics. Caballero et al. (2015) produced a high-affinity monoclonal antibody against S. aureus alpha-toxin and proved its effectiveness as a therapy for S. aureus–mediated keratitis (Caballero et al., 2015). Bacteriophage-derived lytic proteins such as endolysins have been investigated as antimicrobials. Hence, endolysin technology for killing of S. aureus has been reported in the recent past (Schmelcher et al., 2012; Roach and Donovan, 2015). In addition to this, antimicrobial blue light therapy has been reported as a potential alternative or a combinatorial therapy for treatment of keratitis-mediated by S. aureus (Zhu et al., 2017).
Native And Acquired Resistance To Infection With Cryptococcus Neoformans
Hans H. Gadebusch in Phagocytes and Cellular Immunity, 2020
Conditions that trigger the release of lysosomal enzymes from leukocytes (antigenantibody complexes, complement reactions, phagocytosis, and inflammatory substances) as well as blood coagulation can also trigger the release of β-lysin (plakin) from platelets in the milieu of the peritoneal cavity and elsewhere.81 This nonenzymatic protein has also been shown to possess potent anticryptococcal activity.42 The lysosomal enzymes and LCP in the peritoneal cavity or other sites of local inflammation may also attack the intracellular matrix of connective tissue resulting in the generation of cationic polyelectrolytes such as histone, and anionic polyelectrolytes such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), hyaluronic acid, and a variety of mucopolysaccharides. Histones42 like other cationic substances described earlier are fungicidal to cryptococcal cells.
Liver Diseases
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Normal levels of bilirubin in the serum are between 0.2 and 0.8 mg/dl. The bilirubin level is determined by the relative rate at which bile pigments enter or leave the circulation. Bilirubin is tightly bound to albumin, 2 mol of pigment to each protein molecule, corresponding to the normal amount of unconjugated bilirubin in the serum of adults.429,591 Minor amounts are found in globulin fractions. The excess bilirubin is rapidly metabolized, first to yellow oxidation products which are still partly associated with albumin, then further to colorless derivatives which bind preferably to globulins. The bilirubin phenolic hydroxyl groups and the protein amino groups play a part in the bond between the pigment and albumin. Probably, lysine residues provide the free amino groups. If these lysin residues are blocked by reactions with methylisourea, the binding capacity of the albumin is considerably reduced. Other properties of the albumin molecule are also important since other proteins with high lysine content, for example, γ-globulin, show no affinity to bilirubin. Bilirubin diglucuronide is also bound to serum albumin. There are four absorption sites for the conjugate per albumin molecule. Similarly to free bilirubin, an interaction between hydroxyl and amino groups takes place in the binding of bilirubin diglucuronate.68,227
Bacteriophage endolysins as a potential weapon to combat Clostridioides difficile infection
Published in Gut Microbes, 2020
Shakhinur Islam Mondal, Lorraine A. Draper, R Paul Ross, Colin Hill
Bacteriophage endolysins have a unique attribute in comparison to intact phages and antibiotics, in that resistance development is an extremely rare event. Generally, antibiotics work by inhibiting essential metabolic pathways of bacteria leading to cell death.101 However, bacteria have found ways to overcome this adverse situation by using alternative metabolic pathways. It is difficult for bacteria to find means of resistance to endolysin as they bind to and degrade highly conserved peptidoglycan targets within the cell wall.102 Any mutations leading to endolysin resistance would be damaging to the integrity of the cell and thus a very rare event.103 Although no attempts have been made to study lysin-resistance development in C. difficile, there are some studies using other bacterial strains that have investigated repeated lysin exposure and revealed resistance did not develop to either native or engineered phage lysins.40,104-106 Some CWHs of C. difficile have more than one catalytic domain and this theoretically lowers the chance of mutation in multiple target sites in bacteria. Similar observations have been made with S. aureus endolysins.107
Factors determining phage stability/activity: challenges in practical phage application
Published in Expert Review of Anti-infective Therapy, 2019
Ewa Jończyk-Matysiak, Norbert Łodej, Dominika Kula, Barbara Owczarek, Filip Orwat, Ryszard Międzybrodzki, Joanna Neuberg, Natalia Bagińska, Beata Weber-Dąbrowska, Andrzej Górski
Metals may be a crucial factor influencing phage activity. They are important because of their role, e.g. in phage adsorption, binding lytic enzymes and retaining their activity [42,87–89]. The presence of calcium increases the adsorption rate of the phage and penetration of the phage genome into the host cell. Calcium ions supplemented in soft agar during the phage titration process significantly increased the phage titer. During the isolation those ions increase the isolation frequency and the final phage yield [42]. It was also demonstrated that the Ts2631 endolysin requires the divalent metal ions Zn2+, Ca2+, and Mn2+ for its lytic activity [88]. Probable increased interaction of the endolysin with a peptidoglycan backbone is mediated by Ca2+ metal ions. Some peptidases possess a catalytically active Zn2+ ion, which is tetrahedrally coordinated by two histidine side chains, an aspartate and a water molecule. The coordinating water molecule is activated by the Zn2+ ion together with another residue that acts as a general base to promote nucleophilic attack of the substrate peptide carbonyl group. The resulting tetrahedral intermediate is again stabilized by the Zn2+ ion [90]. For the Ca2+ ion it was found that it increases substrate affinity by binding to two aspartate residues of aminopeptidase A and interacting with an acidic side chain of the substrate [91]. It is believed that this might also be the case for phage endolysins and the interaction of the catalytic domain with the D-glutamic acid residue of the peptidoglycan peptide stem [92].
The novel endolysin XZ.700 effectively treats MRSA biofilms in two biofilm models without showing toxicity on human bone cells in vitro
Published in Biofouling, 2021
Jesse W. P Kuiper, Jolanda M. A Hogervorst, Bjorn L. Herpers, Astrid D. Bakker, Jenneke Klein-Nulend, Peter A. Nolte, Bastiaan P. Krom
Interestingly, higher endolysin concentrations and longer exposure showed a trend in less efficacy in the static model. Two possible explanations can be offered: high concentrations might evoke competitive inhibition between binding and cutting sites of the endolysin through occupation of the bacterial surface, and longer exposure to the agent might provide new nutrients (of killed micro-organisms) to still living bacteria and thus initiate regrowth. In the flow model, the highest concentrations were not tested, but regrowth was not seen after XZ.700 treatment. This is not unexpected, as cell debris (including nutrients) are flushed away during flow.
Related Knowledge Centers
- Archaea
- Autolysin
- Autolysis
- Bacteriophage
- Cell Wall
- Hydrolase
- Lytic Cycle
- Peptidoglycan
- Virus
- Pseudopeptidoglycan