  Small open reading frames are understudied as they have been historically
excluded from genome annotations. However, evidence for the functional
significance of small proteins in various cellular processes accumulates.
Proteins with less than 70 residues can also confer resistance to antimicrobial
compounds, including intracellularly-acting protein toxins, membrane-acting
antimicrobial peptides and various small-molecule antibiotics. Such herein
coined Small Antimicrobial Resistance Proteins (SARPs) have emerged on
evolutionary timescales or can be enriched from protein libraries using
laboratory evolution. Our review consolidates existing knowledge on SARPs and
highlights recent advancements in proteomics and genomics that reveal pervasive
translation of unannotated genetic regions into small proteins that show
features of known SARPs. The potential contribution of small proteins to
antimicrobial resistance is awaiting exploration.
