Cerebellar and brainstem stroke possibly associated with booster dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine.

As COVID-19 vaccination becomes widely available and administered globally, there have been several reports of side effects attributed to the vaccine. This report highlights a patient who developed stroke 2 days following the administration of the COVID-19 vaccine, although its association remains uncertain. A man in his late 30s developed acute neurological symptoms 2 days after receiving the booster dose of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine. History and neurological examination suggested a posterior circulation stroke, which was confirmed by MRI, as a right-sided posterior inferior cerebellar artery stroke. Full workup did not suggest other causes of the stroke. Due to the patient's age and well-controlled risk factors, it was presumed to be a rare adverse effect of the vaccine. Medical management with aspirin, statin therapy and rehabilitation led to the improvement of symptoms and enabled ongoing restoration of function. Further cases of stroke following administration of COVID-19 vaccine have been documented in the literature, but the association is yet to be established.

Directed Evolution Reveals the Functional Sequence Space of an Adenylation Domain Specificity Code.

Nonribosomal peptides are important natural products biosynthesized by nonribosomal peptide synthetases (NRPSs). Adenylation (A) domains of NRPSs are highly specific for the substrate they recognize. This recognition is determined by 10 residues in the substrate-binding pocket, termed the specificity code. This finding led to the proposal that nonribosomal peptides could be altered by specificity code swapping. Unfortunately, this approach has proven, with few exceptions, to be unproductive; changing the specificity code typically results in broadened specificity or poor function. To enhance our understanding of A domain substrate selectivity, we carried out a detailed analysis of the specificity code from the A domain of EntF, an NRPS involved in enterobactin biosynthesis in Escherichia coli. Using directed evolution and a genetic selection, we determined which sites in the code have strict residue requirements and which are tolerant of variation. We showed that the EntF A domain, and other l-Ser-specific A domains, have a functional sequence space for l-Ser recognition, rather than a single code. This functional space is more expansive than the aggregate of all characterized l-Ser-specific A domains: we identified 152 new l-Ser specificity codes. Together, our data provide essential insights into how to overcome the barriers that prevent rational changes to A domain specificity.