Cell density and mobility protect swarming bacteria against antibiotics

Abstract

Swarming bacteria move in multicellular groups and exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. We find that high densities promote bacterial survival, even in a nonswarming state, but that the ability to move, as well as the speed of movement, confers an added advantage, making swarming an effective strategy for prevailing against antimicrobials. We find no evidence of induced resistance pathways or quorum-sensing mechanisms controlling this group resistance, which occurs at a cost to cells directly exposed to the antibiotic. This work has relevance to the adaptive antibiotic resistance of bacterial biofilms.

Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient

“…This type of adaptive resistance is reminiscent of the non-genetic resistance that some bacterial species exhibit when engaging in collective swarming motility (Kim et al, 2003;Overhage et al, 2008;Butler et al, 2010;Roth et al, 2013). Nonresistant swarming Salmonella enterica populations were previously shown to migrate from an antibiotic-free agar surface onto an agar surface containing lethal doses of an antibiotic (Butler et al, 2010).…”

“…The mechanisms underlying the non-inherited antibiotic refractoriness of bacteria are diverse, and only partially understood (Hogan and Kolter, 2002;Lewis, 2010;Balaban et al, 2013;Orman and Brynildsen, 2013). Some forms of tolerance to lethal doses of antibiotics, for example, persistence, are associated with a strongly reduced metabolic activity, whereas others rely on active responses that confer (collective) adaptive resistance (Balaban et al, 2004;Butler et al, 2010;Lewis, 2010;Nguyen et al, 2011;Wakamoto et al, 2013;Meredith et al, 2015). Little is known regarding the role of antibiotic concentration gradients in facilitating the survival of nonresistant bacteria.…”

Adaptor-mediated Lon proteolysis restrictsBacillus subtilishyperflagellation

“…Further, swimmer and swarmer cells are physiologically distinct as transitioning to surfaces includes a lag period of immobility that may be a time for cellular differentiation in response to surface contact. Importantly, differentiation to a swarmer cell has been associated with enhanced virulence, elevated antimicrobial resistance, and increased flagellar density (25,(27)(28)(29)(30)(31)(32). The mechanism of surface contact recognition and subsequent signal transduction is unknown save that the transition may be controlled by master regulators of flagellar biosynthesis and the Lon protease (33,34).…”

Emergence of Lévy walks in systems of interacting individuals

“…However, it is still an open question how Lévy walks emerge in systems of interacting self-propelled particles. The current theory of Lévy walk [8] assumes noninteracting particles and power-law distribution of traveled distances from the inception.The collective behavior of large groups of interacting individuals such as bird flocks, fish schools, and the collective migration of cells or bacteria is another rapidly growing area of active matter research [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. There exist two main types of models used for a collective behavior: (1) Lagrangian models describing the movements of self-propelled particles in terms of nonlinear equations for the positions and velocities of all particles [20][21][22][23], and (2) kinetic models involving partial differential equations for the population densities [24][25][26][27][28][29][30].…”