Small antimicrobial resistance proteins (SARPs): Small proteins conferring antimicrobial resistance

TL;DR

This review discusses small proteins called SARPs that can confer antimicrobial resistance, emphasizing recent genomic and proteomic discoveries and the need for further functional exploration.

Contribution

It consolidates current knowledge on SARPs and highlights recent advances in detection methods, emphasizing the potential role of small proteins in antimicrobial resistance.

Findings

Small proteins can confer resistance to various antimicrobials

Recent genomics and proteomics reveal widespread translation of small proteins

The functional role of SARPs in resistance is still largely unexplored

Abstract

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.