The methods and compositions described herein relate to the delivery of polypeptides to a target cell, e.g. by utilizing engineered non-pathogenic bacteria comprising a type three secretion system (T3SS) and T3SS-compatible substrates. In one aspect, described herein are non-pathogenic microbial cells that have been engineered to express both a functional type three secretion system (T3SS) and at least one polypeptide that is compatible with the T3SS. Due to the wide variety of polypeptides that can be delivered to a target eukaryotic cell using the compositions and systems described herein, a commensurately wide variety of applications is contemplated, e.g. therapeutics and reprogramming.