Bacterial Swarming Reduces Proteus mirabilis and Vibrio parahaemolyticus Cell Stiffness and Increases β-Lactam Susceptibility

Abstract

Swarmer cells of the Gram-negative uropathogenic bacteria Proteus mirabilis and Vibrio parahaemolyticus become long (>10 to 100 μm) and multinucleate during their growth and motility on polymer surfaces. We demonstrated that the increasing cell length is accompanied by a large increase in flexibility. Using a microfluidic assay to measure single-cell mechanics, we identified large differences in the swarmer cell stiffness (bending rigidity) of P. mirabilis (5.5 × 10−22 N m2) and V. parahaemolyticus (1.0 × 10−22 N m2) compared to vegetative cells (1.4 × 10−20 N m2 and 2.2 × 10−22 N m2, respectively). The reduction in bending rigidity (∼2-fold to ∼26-fold) was accompanied by a decrease in the average polysaccharide strand length of the peptidoglycan layer of the cell wall from 28 to 30 disaccharides to 19 to 22 disaccharides. Atomic force microscopy revealed a reduction in P. mirabilis peptidoglycan thickness from 1.5 nm (vegetative cells) to 1.0 nm (swarmer cells), and electron cryotomography indicated changes in swarmer cell wall morphology. P. mirabilis and V. parahaemolyticus swarmer cells became increasingly sensitive to osmotic pressure and susceptible to cell wall-modifying antibiotics (compared to vegetative cells)—they were ∼30% more likely to die after 3 h of treatment with MICs of the β-lactams cephalexin and penicillin G. The adaptive cost of “swarming” was offset by the increase in cell susceptibility to physical and chemical changes in their environment, thereby suggesting the development of new chemotherapies for bacteria that leverage swarming for the colonization of hosts and for survival. IMPORTANCE Proteus mirabilis and Vibrio parahaemolyticus are bacteria that infect humans. To adapt to environmental changes, these bacteria alter their cell morphology and move collectively to access new sources of nutrients in a process referred to as “swarming.” We found that changes in the composition and thickness of the peptidoglycan layer of the cell wall make swarmer cells of P. mirabilis and V. parahaemolyticus more flexible (i.e., reduce cell stiffness) and that they become more sensitive to osmotic pressure and cell wall-targeting antibiotics (e.g., β-lactams). These results highlight the importance of assessing the extracellular environment in determining antibiotic doses and the use of β-lactam antibiotics for treating infections caused by swarmer cells of P. mirabilis and V. parahaemolyticus.

Electrochemical Biosensors for the Detection of SARS-CoV-2 and Other Viruses

“…Cabral-Miranda et al [122] developed a novel immunosensor that contained recombinant ZIKV non-structural protein 1 (NS1) and recombinant domain III of envelope protein (EDIII) as two antigens for the detection of anti-NS1 and anti-EDIII antibodies, respectively. NS1 is a replicase component that is secreted into the extracellular matrix along with the ZIKV virion, while the envelope protein is the major glycoprotein in the viral envelope [124,125]. EDIII, in particular, is involved with receptor binding and fusion with the host cell, hence antibodies against it prevent the virus from entering into the cell [124].…”

The physics of active polymers and filaments

“…240,241 Some cells, such as Proteus mirabilis or Vibrio parahaemolyticus become rather elongated (> 10 − 100 µm) and polymer-like. 43 Since they are propelled by flagella, which are shorter than the body length and distributed all over the body, locomotion of individual cell is mainly tangential. Figure 13 shows that such cells can undergo large conformational changes from nearly rodlike to strongly bend structures while moving collectively in a film with other cells.…”

“…Image of P. mirabilis swarmer cells in a colony actively moving across a surface. 43 The green, generally straight cell illustrates the ability of swarmer cells to bend substantially. "G. K. such as a melt-like structures with topological defects.…”

“…6,38,41 Numerous biological microswimmers are rather elongated and polymer-or filament-like, undergoing shape changes during migration. A particular example are elongated swarming bacteria, propelled by flagella, such as Proteus mirabilis, Vibrio parahaemolyticus, 42,43 or Serratia marcescens, 44 which exhibit an intriguing collective behavior. Other microswimmers organize in chain-like structures, for example planktonic dinoflagellates 45,46 or Bacillus subtilis bacteria during biofilm formation.…”

Configuration and dynamics of a self-propelled diblock copolymer chain

“…[7][8][9][10][11][12][13][14][15][16][17][18][19] Polymeric active matters or active polymers (APs) are not unusual in living systems. Some examples include microtubules/microfilaments driven by motor proteins, 20,21 DNA/RNA molecules in transcription, 22 slender bacteria, 23 algae or bacteria that can organize into a chain-like structure, 24 and macroscopic worms. 25,26 Besides the bio-polymeric active matter, chains of self-propelled colloidal particles have already been realized in experiments.…”