Cascade -reaction containers generating reactive oxygen species (ROS) as an alternative for antibioticbased strategies for bacterial infection control, require endogenous oxygen -sources and ROS-generation close to or preferably inside target bacteria. Here, this is achieved by cetyltrimethylammonium-chloride (CTAC) assisted in situ metabolic labeling and incorporation of mesoporous SiO 2 -nanoparticles, dualloaded with glucose-oxidase and Fe 3 O 4 -nanoparticles as cascade -reaction containers, inside bacterial cell walls. First, azide-functionalized d-alanine (D -Ala -N 3 ) was inserted in cell wall peptidoglycan layers of growing Gram-positive pathogens. In Gram -negatives, this could only be achieved after outer lipidmembrane permeabilization, using a low concentration of CTAC. Low concentrations of CTAC had no adverse effect on in vitro blood clotting or hemolysis nor on the health of mice when blood -injected. Next, dibenzocyclooctyne-polyethylene-glycol modified, SiO 2 -nanoparticles were in situ click -reacted with dAla -N 3 in bacterial cell wall peptidoglycan layers. Herewith, a two-step cascade -reaction is facilitated inside bacteria, in which glucose-oxidase generates H 2 O 2 at endogenously -available glucose concentrations, while subsequently Fe 3 O 4 -nanoparticles catalyze generation of center dot OH from the H 2 O 2 generated. Generation of center dot OH inside bacterial cell walls by dual -loaded mesoporous SiO 2 -nanoparticles yielded more effective in vitro killing of both planktonic Gram-positive and Gram-negative bacteria suspended in 10 % plasma than SiO 2 -nanoparticles solely loaded with glucose-oxidase. Gram-positive or Gram-negative bacterially induced sepsis in mice could be effectively treated by in situ pre-treatment with tail -vein injected CTAC and d -Ala -N 3 , followed by injection of dual -loaded cascade -reaction containers without using antibiotics. This makes in situ metabolic incorporation of cascade -reaction containers as described attractive for further investigation with respect to the control of other types of infections comprising planktonic bacteria. Statement of Significance In situ metabolic -incorporation of cascade -reaction -containers loaded with glucose-oxidase and Fe 3 O 4 nanoparticles into bacterial cell -wall peptidoglycan is described, yielding ROS-generation from endogenous glucose, non-antibiotically killing bacteria before ROS inactivates. Hitherto, only Gram -positives could be metabolically -labeled, because Gram -negatives possess two lipid -membranes. The outer membrane impedes direct access to the peptidoglycan. This problem was solved by outer -membrane permeabilization using a quaternary -ammonium compound. Several studies on metabolic -labeling perform crucial labeling steps during bacterial -culturing that in real -life should be part of a treatment. In situ metabolic -incorporation as described, can be applied in well -plates during in vitro experiments or in the body as during in vivo animal experiments. Surprisingly, metabolic -incorporation proceeded unhampered in blood and a murine, bacterially -induced sepsis could be well treated.