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Bacteriology of Ophthalmic Infections
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
Arumugam Priya, Shunmugiah Karutha Pandian
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).
Could bacteriophages be the answer to the COVID-19 crisis?
Published in Expert Review of Anti-infective Therapy, 2021
Antal Martinecz, Marcin W. Wojewodzic
Endolysins may circumvent some of the issues related to classical phage therapy. Endolysins are enzymes used by bacteriophages at the end of their replication cycle to disrupt cell walls, releasing progeny phages, and killing the bacterial cells in the process. These enzymes, and their derivatives, represent an alternative to antibiotics [6], as they display a high degree of host (bacterial) specificity. As such they are harmless to ‘human-friendly’ bacteria and, as they do not replicate themselves, there is no risk of them mutating and the dose to the patient can be precisely controlled. Endolysins will be important to combat the emergence of antibiotic resistance, however similarly to phage therapy, additional diagnostic tests would be necessary to identify the bacteria responsible for co-infections. Finally, both phage therapy and endolysins have limited potential, as bacterial co-infections are present in only a small proportion COVID-19 cases. This means that we would need to allocate large amounts of resources to solve a problem that can already be mitigated by the use of antibiotics [7]. Provided, that there are appropriate measures in place to reduce their use.
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
Generally, endolysins have a conserved biological function directed at lysing infected bacterial cells. However, constant evolutionary pressure between bacteriophage and host bacteria has resulted in significant biochemical and structural variations among endolysins.62 Endolysins against Gram-positive and Gram-negative organisms are categorized differently due to the composition of the cell walls of their targets. Gram-positive endolysins are modular in structure with one or two N-terminal enzymatically active domains (EADs) and one or more C-terminal cell-wall binding domains (CBDs), these domains are usually connected by a short linker region.62,63 EADs contain the catalytic mechanism of endolysins, disrupting specific bonds within the bacterial peptidoglycan, whereas CBDs bind to constituents of cell walls to promote EAD localization to its target site and enhance catalytic efficiency. However, sometimes greater lytic activity has been observed in truncated endolysins containing only EADs.20,64 Gram-negative endolysins usually have single globular catalytic domain and lack a CBD.65,66 There have been some reports for Gram-negative endolysins that indicate a modular organization with a CBD at the N-terminus and EAD at the C-terminus which is inverse architecture typical to most Gram-positive endolysins.67,68
Alternatives to antibiotics in an era of difficult-to-treat resistance: new insights
Published in Expert Review of Clinical Pharmacology, 2019
Jordi Rello, Francesca Romana Parisella, Antonio Perez
Sal200 is composed of a recombinant form of the phage endolysin SAL-1 (rSAL-1). Endolysins are a common area of research, their mechanism of action involves bacterial cell wall destruction and release of phage progeny. Preclinical trial of Sal200 in mice with a MRSA infection demonstrated a reduced bacterial count in the bloodstream and spleen, with even lower rates achieved when combined to antibiotics [28]. In a phase IIa clinical trial (NCT01855048) a total of 34 volunteers received Sal200, which demonstrated strong antibacterial activity and no serious adverse events were observed [29]. Another lysin, CF-301, is being tested in a phase 2 trial (NCT03163446) in hospitalized patients with MRSA bacteremia and endocarditis [30]. Other studies on lysins are being developed and are currently in preclinical stages [31–33].