Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has beenconsiderednecessaryforrepair.Pore-formingproteinsareimportant,bothinpathogeninvasionandhostimmunity.However, their roles in wound healing and tissue repair are unclear. bg-crystallin fused aerolysin-like protein(a-subunit)andtrefoilfactor(b-subunit)complex(bg-CAT)isacomplexofabacterialpore-formingtoxinaerolysin-likeproteinandtrefoilfactoridentifiedinthefrogBombinamaxima.Inthisstudy,weestablishedmousecutaneouswound models to explore the effects of bg-CAT on skin wound healing. bg-CAT accelerated the healing of full-thickness wounds by improving re-epithelialization. This complex relieved dermal edema and promoted scarlesshealing. bg-CAT treatment resulted in a rapid release of IL-1b, which initiated an acute inflammation response intheearlystageofhealing.Meanwhile,theexpressionlevelsofTGF-b1,VEGF,andbFGFandtherecruitmentofM2macrophages around the wound significantly increased after bg-CAT treatment. bg-CAT protected skin woundsagainst methicillin-resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound.Overall, our results suggest that bg-CAT can promote tissue repair and protect skin wounds against antibiotic-resistant bacterial infection by triggering the acute inflammatory response. This is the firstexample that aerolysin-likepore-formingproteinswidelyexistinginplantsandanimalsmayactinwoundhealingandtissuerepair.—Gao,Z.-H., Deng, C.-J., Xie, Y.-Y., Guo, X.-L., Wang, Q.-Q., Liu, L.-Z., Lee, W.-H., Li, S.-A., Zhang, Y. Pore-forming toxin-like protein complex expressed by frog promotes tissue repair. FASEB J. 33, 000–000 (2019). www.fasebj.org