UC Irvine

The everlasting battles between humans and bacteria entered a new stage with the discovery of antibiotics that saved millions of lives in the 20th century. However, the rise of antibiotic-resistant strains, often resistant to multiple classes of antibiotics, poses a renewed threat to human health. Compared to the quick and swift evolution of the resistant phenotypes, the development of new antibiotics has stagnated for decades, exacerbated by a limited understanding of the evolutionary mechanisms driving antibiotic resistance.

Bacteria, thriving in diverse and harsh environments, have evolved myriad strategies to survive various stresses, including starvation, osmotic stress, heavy metals, antimicrobial agents, and so on. Understanding bacterial responses to these stresses is critical for delaying the emergence of antibiotic resistance mutations, reducing pathogenic bacterial tolerance to adverse environments, and optimizing industrial production processes.

In this work, different tools were deployed to detect, visualize, quantify, and eventually predict bacterial behavior under different stresses. A widely used molecule resazurin was found to be an ideal candidate for a novel accurate, cheap, and highly effective bioassay that could monitor intracellular NADH level and bacterial stress response in real time. An algorithm depicting bacterial metabolite profile was developed to detect minor heavy metal contamination in the drinking water, harnessing bacteria as powerful indicators to pollution. Lastly, we adapted a novel model to study the persistent bacterial community known as biofilms. Biofilm attaches to biotic or abiotic surfaces, is resistant to adverse conditions, and causes great pain to our patients. We simulated the osmotic pressure perturbation in vivo to explain the mechanisms of cross-protection between different stresses and found inspiration to postulate new strategies to eliminate stubborn bacterial communities.