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In patients undergoing allo-HCT, low gastrointestinal (GI) microbial diversity is associated with adverse outcomes including bloodstream infections (BSIs) and acute graft-versus-host disease (aGvHD). SER-155 is an investigational cultivated oral microbiome therapeutic designed to engraft in the GI tract, promote GI barrier integrity, and reduce pathogen domination. SER-155-001 is a 2-part, Phase 1b study evaluating the safety, pharmacokinetics (PK), and efficacy of SER-155 in adults undergoing allo-HCT. We present preliminary data from the open-label Cohort 1 through Day 100 post-HCT.

Stationary-phase mutation (a subset of which was previously called adaptive mutation) occurs in apparently nondividing, stationary-phase cells exposed to a nonlethal genetic selection. In one experimental system, stationary-phase reversion of an Escherichia coliF'-borne lacframeshift mutation occurs by a novel molecular mechanism that requires homologous recombination functions of the RecBCD system. Chromosomal mutations at multiple loci are detected more frequently in Lacstationary-phase revertants than in cells that were also exposed to selection but did not become Lac. Thus, mutating cells represent a subpopulation that experiences hypermutation throughout the genome. This paper summarizes current knowledge regarding stationary-phase mutation in the lacsystem. Hypotheses for the mechanism of chromosomal hypermutation are discussed, and data are presented that exclude one hypothetical mechanism in which chromosomal mutations result from Hfr formation.

Escherichia colicells are capable of complex regulatory responses to environmental conditions and stresses. In some circumstances, the response includes an increase in the mutation rate, effectively mutagenizing the genome. The classic example is the SOS response to DNA damage. Recent work indicates that other environmental stresses can also result in mutation of the genome. Modulation of mutation rate may be a more prevalent stress response than previously thought. In this review we focus on genome-wide mutation inE. colicells subjected to a nonlethal genetic selection for reversion of alacframeshift allele. Reversion of thelacframeshift allele occurs via a novel mechanism that requires homologous recombination functions, and is enhanced by transiently diminished postsynthesis mismatch repair. A model for recombination-dependent stationary-phase mutation will be presented and its relevance for genome-wide mutation discussed.