Exposure of Escherichia coli to H2O2 leads to two kinetically distinguishable modes of killing: mode I killing occurs maximally near 2 mM H2O2, whereas mode II killing is essentially independent of H2O2 concentrations up to 20 mM. A major portion of H2O2 toxicity is attributed to DNA damage caused by the iron-mediated Fenton reaction. By studying DNA damage during Fenton reactions in vitro, the...

A mathematical model of biofilm dynamics was used to investigate the protection from antibiotic killing that can be afforded to microorganisms in biofilms based on a mechanism of localized nutrient limitation and slow growth. The model assumed that the rate of killing by the antibiotic was directly proportional to the local growth rate. Growth rates in the biofilm were calculated by using the l...

In this report we describe experiments to investigate a simple virulence model in which Pseudomonas aeruginosa PAO1 rapidly paralyzes and kills the nematode Caenorhabditis elegans. Our results imply that hydrogen cyanide is the sole or primary toxic factor produced by P. aeruginosa that is responsible for killing of the nematode. Four lines of evidence support this conclusion. First, a transpos...

We showed previously that the competition between bacterial killing by neutrophils and bacterial growth in stirred serum-containing suspensions could be modeled as the competition between a first-order reaction (bacterial growth) and a second-order reaction (bacterial killing by neutrophils). The model provided a useful parameter, the critical neutrophil concentration (CNC), below which bacteri...

Although Staphylococcus aureus is incapable of intracellular multiplication in cultured mouse peritoneal macrophages, it is killed at a much slower rate than the avirulent Staphylococcus epidermidis. In addition to the presence of capsular material which inhibits phagocytosis of specific strains of S. aureus, the data show that a number of cellular and environmental factors affect the functiona...

T cells genetically modified to express a CD19-specific chimeric antigen receptor (CAR) for the investigational treatment of B cell malignancies comprise a heterogeneous population, and their ability to persist and participate in serial killing of tumor cells is a predictor of therapeutic success. We developed Timelapse Imaging Microscopy In Nanowell Grids (TIMING) to dynamically analyze thousa...

We introduce optogenetic tools (designated LiPOP) that enable photoswitchable necroptosis and pyroptosis in live cells with varying kinetics. The LiPOP allow us to reconstruct the key molecular steps involved these two non-apoptotic cell death pathways by harnessing power of light. further demonstrate use LiPOP, itself or coupled bioluminescence, achieve optochemical killing bacteria cancer viv...

Currently available antimicrobials exhibit broad killing with regard to bacterial genera and species. Indiscriminate killing of microbes by these conventional antibiotics can disrupt the ecological balance of the indigenous microbial flora, often resulting in negative clinical consequences. Species-specific antimicrobials capable of precisely targeting pathogenic bacteria without damaging benig...

The ability of serum complement to kill Gram-negative bacteria requires assembly of the membrane attack complex (MAC) on the cell surface. The molecular events that lead to cell killing after MAC assembly are unknown. We have investigated the effect of C9 on bacterial survival in the presence and absence of its receptor, the C5b-8 complex, on the outer membrane. A fluorescence assay of the memb...