PBP-A, a cyanobacterial dd-peptidase with high specificity for amidated muropeptides, exhibits pH-dependent promiscuous activity harmful to <em>Escherichia coli</em>

\ua9 The Author(s) 2024. Penicillin binding proteins (PBPs) are involved in biosynthesis, remodeling and recycling of peptidoglycan (PG) in bacteria. PBP-A from Thermosynechococcus elongatus belongs to a cyanobacterial family of enzymes sharing close structural and phylogenetic proximity to class A β-lactamases. With the long-term aim of converting PBP-A into a β-lactamase by directed evolution, we simulated what may happen when an organism like Escherichia coli acquires such a new PBP and observed growth defect associated with the enzyme activity. To further explore the molecular origins of this harmful effect, we decided to characterize deeper the activity of PBP-A both in vitro and in vivo. We found that PBP-A is an enzyme endowed with dd-carboxypeptidase and dd-endopeptidase activities, featuring high specificity towards muropeptides amidated on the d-iso-glutamyl residue. We also show that a low promiscuous activity on non-amidated peptidoglycan deteriorates E. coli’s envelope, which is much higher under acidic conditions where substrate discrimination is mitigated. Besides expanding our knowledge of the biochemical activity of PBP-A, this work also highlights that promiscuity may depend on environmental conditions and how it may hinder rather than promote enzyme evolution in nature or in the laboratory

What are the roles involved in establishing and maintaining informational continuity of care withinfamily practice? A systematic review

Abstract Background Central to establishing continuity of care is the development of a relationship between doctor and patient/caregiver. Transfer of information between these parties facilitates the development of continuity in general; and specifically informational continuity of care. We conducted a systematic review of published literature to gain a better understanding of the roles that different parties – specifically doctors, patients, family caregivers, and technology – play in establishing and maintaining informational continuity of care within family practice. Methods Relevant published articles were sought from five databases. Accepted articles were reviewed and appraised in a consistent way. Fifty-six articles were retained following title and abstract reviews. Of these, 28 were accepted for this review. Results No articles focused explicitly on the roles involved in establishing or maintaining informational continuity of care within family practice. Most informational continuity of care literature focused on the transfer of information between settings and not at the first point of contact. Numerous roles were, however, were interpreted using the data extracted from reviewed articles. Doctors are responsible for record keeping, knowing patients' histories, recalling accumulated knowledge, and maintaining confidentiality. Patients are responsible for disclosing personal and health details, transferring information to other practitioners (including new family doctors), and establishing trust. Both are responsible for developing a relationship of trust. Technology is an important tool of informational continuity of care through holding important information, providing search functions, and providing a space for recorded information. There is a significant gap in our knowledge about the roles that family caregivers play. Conclusion The number of roles identified and the interrelationships between them indicates that establishing and maintaining informational continuity of care within family practice is a complex and multifaceted process. This synthesis of roles provided serves as an important resource for continuity of care researchers in general, for the development of continuity of care quality indicators, and for the practice of family medicine.</p