Introduction:　Wound　infections　and　formation　of　biofilms　caused　by　multidrug-resistant　bacteria　have　constituted　a　series　of　wound　deteriorated　and　life-threatening　problems.　The　in　situ　resisting　bacterial　adhesion,　killing　multidrug-resistance　bacteria,　and　releasing　dead　bacteria　is　strongly　required　to　supply　a　gap　of　existing　sterilization　strategies.　Objectives:　This　study　aims　to　present　a　facile　approach　to　construct　a　bacteria-responsive　hydrogel　with　switchable　antimicrobial-antifouling　properties　through　a　“resisting-killing-releasing”　method.　Methods:　The　smart　bacteria-responsive　hydrogel　was　constructed　by　two-step　immersion　strategy:　a　simple　immersion-coating　process　to　construct　Polydopamine　(pDA)　coatings　on　the　surface　of　a　gelatin-chitosan　composite　hydrogel　and　followed　by　grafting　of　bactericidal　quaternary　ammonium　chitosan　(QCS)　as　well　as　pH-responsive　PMAA　to　this　pDA　coating.　The　in　vitro　antimicrobial　activity,　biocompatibility　and　the　in　vivo　wound　healing　effects　in　a　mouse　MRSA-infected　full-thickness　defect　model　of　the　hydrogel　were　further　evaluated.　Results:　Assisted　by　polydopamine　coating,　the　pH-responsive　PMAA　and　bactericidal　QCS　are　successfully　grafted　onto　a　gelatin-chitosan　composite　hydrogel　surface　and　hydrogels　maintain　the　adequate　mechanical　properties.　At　physiological　conditions,　the　PMAA　hydration　layer　endows　the　hydrogel　with　resistance　to　initial　bacterial　attachment.　Once　bacteria　colonize　and　acidize　local　environment,　the　swelling　PMAA　chains　tend　to　collapse　then　expose　the　bactericidal　QCS,　realizing　the　on-demand　kill　bacteria.　Moreover,　the　dead　bacteria　can　be　released　and　the　hydrogel　will　resume　the　resistance　due　to　hydrophilicity　of　PMAA　at　increased　pH,　endowing　the　surface　renewable　ability.　In　vitro　and　in　vivo　studies　demonstrate　the　favorable　biocompatibility　and　wound　healing　capacity　of　hydrogels　that　can　inhibit　infection　and　further　facilitate　granulation　tissue,　angiogenesis,　and　collagen　synthesis.　Conclusion:　This　strategy　provides　a　novel　methodology　for　the　development　and　design　of　smart　wound　dressing　to　combat　multidrug-resistant　bacteria　infections.　©　2024