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Modi, Z.

Publications and source records attributed to Modi, Z..

2 recordsLinked to original sources

Flow rapidly replenishes scarce nutrients to promote bacterial growth

In laboratory settings, bacteria grow in static culture with more nutrients than they require. However, bacteria in nature experience flowing environments that are nutrient limited. Using microfluidics and single cell imaging, we discover that flow promotes growth of the human pathogen Pseudomonas aeruginosa at surprisingly low nutrient concentrations. In static environments, cells require high nutrient concentrations as they steadily consume non-renewable resources. In flowing environments, cells grow robustly at very low nutrient concentrations that are constantly replenished. Our simulation-guided experiments show how stopping flow halts growth within minutes and varying flow impacts growth gradients across bacterial populations. By precisely delivering nutrients using microfluidics, we learned that cells in flow can grow on glucose concentrations 1,000 times lower than those observed in typical laboratory experiments. The ultralow glucose concentrations sufficient for growth in flow closely align with the affinity of bacterial glucose transporters, suggesting that bacteria have evolved in flowing environments with scarce nutrients. Collectively, our results emphasize the limits of traditional culturing approaches and highlight how depleted environments can unexpectedly support bacterial growth.

microbiology↗

Fluid flow overcomes antimicrobial resistance by boosting delivery

Antimicrobial resistance is an emerging global threat to humanity. As resistance outpaces development, new perspectives are required. For decades, scientists have prioritized chemical optimization, while largely ignoring the physical process of delivery. Here, we used biophysical simulations and microfluidic experiments to explore how fluid flow delivers antimicrobials into communities of the highly resistant pathogen Pseudomonas aeruginosa. We discover that increasing flow overcomes bacterial resistance towards three chemically distinct antimicrobials: hydrogen peroxide, gentamicin, and carbenicillin. Without flow, resistant P. aeruginosa cells generate local zones of depletion by neutralizing all three antimicrobials through degradation or chemical modification. As flow increases, delivery overwhelms neutralization, allowing antimicrobials to regain effectiveness against resistant bacteria. Additionally, we discover that cells on the edge of a community shield internal cells, and cell-cell shielding is abolished in higher flow regimes. Collectively, our quantitative experiments reveal the unexpected result that physical flow and chemical dosage are equally important to antimicrobial effectiveness. Thus, our results should inspire the incorporation of flow into the discovery, development, and implementation of antimicrobials, and could represent a new strategy to combat antimicrobial resistance.

microbiology↗