Princeton’s Zemer Gitai (Department of Molecular Biology) led an eclectic group of researchers from Princeton’s Departments of Physics, Chemistry, Mechanical and Aerospace Engineering, Molecular Biology, and the Lewis-Sigler Institute for Integrative Genomics to investigate how fluid flow impacts the surface colonization of two bacterial species, Staphylococcus aureus and Enterococcus faecalis, commonly associated with heart valve infections. Their study reveals that both species exhibit a counterintuitive behavior by preferentially colonizing surfaces in high-shear conditions. This preference is not specific to heart valves or host factors but is driven by the bacteria themselves.
Key findings include:
• Distinct mechanisms for flow-dependent colonization: S. aureus and E. faecalis employ different strategies based on their nanocolony morphologies.
• S. aureus: Its clustered morphology and the transport of dispersal signaling molecules mediate flow-dependent colonization. High flow rates increase autoinducer transport, reducing quorum sensing signaling and promoting colonization. Low flow allows quorum sensing autoinducers to accumulate, downregulating adhesins and leading to cell detachment.
• E. faecalis: The mechanical forces acting on its linear chains determine its flow-dependent colonization. Higher flow rates exert greater shear force, pushing the chains closer to the surface and increasing attachment.
• Competition dynamics: In minimal flow conditions, Pseudomonas aeruginosa outcompetes S. aureus, but in high flow, S. aureus dominates, suggesting that flow-dependent colonization provides a competitive advantage.
• Models: The researchers developed a transport-dependent colonization model to explain the flow effects on S. aureus and a mechanics-dependent colonization model for E. faecalis.
• Relevance of Nanocolony morphology: The differing multicellular nanocolony morphologies have previously unappreciated costs and benefits in different environments, like those introduced by fluid flow.
Counterintuitive final cell population in low versus high flow. (A) Schematic of microfluidic chamber used for all flow experiments. A PDMS microfluidic channel, channel dimensions shown, is bonded to a glass coverslip. Following cell loading, a syringe pump is turned on, flowing fresh media through the channel. Cells attached to the coverslip are imaged. (B) Analysis of doubling times for each S. aureus MRSA and E. faecalis in low (red) and high (blue) flow conditions. (C) Representative phase contrast images of S. aureus at 0, 3, and 6 h of low flow (shear rate 40/s). (D) Representative phase contrast images of S. aureus at 0, 3, and 6 h of high flow (shear rate 400/s). (E) Fold change of percent area covered of both low (red) and high (blue) flow experiments for S. aureus. (F) Representative phase contrast images of E. faecalis at 0, 3, and 6 h of low flow (shear rate 40/s). (G) Representative phase contrast images of E. faecalis at 0, 3, and 6 h of high flow (shear rate 400/s). (H) Fold change of percent area covered of both low (red) and high (blue) flow experiments for E. faecalis. Image (Scale bars, 10 μm.) Error bars are SEM.
Hallinen KM, Bodine SP, Stone HA, Muir TW, Wingreen NS, Gitai Z. Bacterial species with different nanocolony morphologies have distinct flow-dependent colonization behaviors. Proc Natl Acad Sci U S A. 2025 Feb 18;122(7):e2419899122. doi: 10.1073/pnas.2419899122. Epub 2025 Feb 10. PMID: 39928871. https://www.pnas.org/doi/epub/10.1073/pnas.2419899122
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