As　the　harm　of　benzalkyl　dimethylammonium　compounds　(BACs)　on　human　health　and　environment　was　discovered,　alkyltrimethyl　ammonium　compound　(ATMAC)　and　dialkyldimethyl　ammonium　compound　(DADMAC),　which　belong　to　quaternary　ammonium　compounds　(QACs),　were　likely　to　replace　BACs　as　the　main　disinfectants.　This　study　simulated　the　iterative　use　of　QACs　to　explore　their　impact　on　resistance　genes　(RGs)　in　nitrification　systems　pre-contaminated　by　BACs.　ATMAC　could　initiate　and　maintain　partial　nitrification.　DADMAC　generated　higher　levels　of　reactive　oxygen　species　and　lactate　dehydrogenase,　leading　to　increased　biological　toxicity　in　bacteria.　The　abundance　of　intracellular　RGs　of　sludge　was　higher　with　the　stress　of　QACs.　DADMAC　also　induced　higher　extracellular　polymeric　substance　secretion.　Moreover,　it　facilitated　the　transfer　of　RGs　from　sludge　to　water,　with　ATMAC　disseminating　RGs　through　si-tnpA-04　and　DADMAC　through　si-intI1.　Sediminibacterium　might　be　potential　hosts　for　RGs.　This　study　offered　insights　into　disinfectant　usage　in　the　post-COVID-19　era.　©　2024　Elsevier　Ltd