Mechanical deformation inhibits growth and migration of S. aureus within submicrometer channels

Bacteria colonize surfaces in the environment and can also penetrate tissues and materials by entering micro- and nano-scale cracks and pores. Staphylococcus aureus has been observed within nanoscale channels in bone that are 2-3 times smaller than cell diameter. Inside the bone, bacteria are protected from host immunity and systemic antibiotics, potentially contributing to chronic and recurrent infections. The physical mechanisms that enable bacteria to enter channels smaller than the cell width are unclear. It has been proposed that bacteria traverse narrow passages through division, such that daughter cells form within small channels and proliferate in chains down the channel length. Here, we use microfluidics to test the idea that S. aureus can traverse submicrometer channels through growth. We examined the net migration of growing cell chains within tapered nanochannels (width ~1.5-0.3 μm). We found that proliferation can facilitate migration, but only to cell deformations of 600 nm (65% cell width). Below 600 nm, mechanical confinement significantly slows or completely inhibits division in single cells. Interestingly, growth arrest occurs independent of the Z-ring assembly and is unrelated to the initial orientation of the division plane. Thus, our findings suggest that it is unlikely for S. aureus to traverse nanoscale channels via division.

Bacteria that colonize materials and tissues within the body can be difficult to remove, even with thorough cleaning and application of antibiotics. Recent studies show that bacteria not only colonize the surfaces of tissues in the body but can also squeeze into naturally occurring pores and channels and thereby gain protection from immune cells and antibiotics. Here, we ask how physical forces and cell growth might enable bacteria to enter small pores within materials. We use microfluidic devices to study the growth and migration of the human pathogenic bacteria, S. aureus.