title: Colonization, competition, and dispersal of pathogens in fluid flow networks.
abstract: The colonization of bacteria in complex fluid flow networks, such as those found in host vasculature, remains poorly understood. Recently, it was reported that many bacteria, including Bacillus subtilis [1], Escherichia coli [2], and Pseudomonas aeruginosa [3, 4], can move in the opposite direction of fluid flow. Upstream movement results from the interplay between fluid shear stress and bacterial motility structures, and such rheotactic-like behavior is predicted to occur for a wide range of conditions [1]. Given the potential ubiquity of upstream movement, its impact on population-level behaviors within hosts could be significant. Here, we find that P. aeruginosa communities use a diverse set of motility strategies, including a novel surface-motility mechanism characterized by counter-advection and transverse diffusion, to rapidly disperse throughout vasculature-like flow networks. These motility modalities give P. aeruginosa a selective growth advantage, enabling it to self-segregate from other human pathogens such as Proteus mirabilis and Staphylococcus aureus that outcompete P. aeruginosa in well-mixed non-flow environments. We develop a quantitative model of bacterial colonization in flow networks, confirm our model in vivo in plant vasculature, and validate a key prediction that colonization and dispersal can be inhibited by modifying surface chemistry. Our results show that the interaction between flow mechanics and motility structures shapes the formation of mixed-species communities and suggest a general mechanism by which bacteria could colonize hosts. Furthermore, our results suggest novel strategies for tuning the composition of multi-species bacterial communities in hosts, preventing inappropriate colonization in medical devices, and combatting bacterial infections.
authors.affiliation: Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Siryaporn
authors.affiliation: Frick Laboratory, Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.
authors.forename: Minyoung Kevin
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Engineering Quad, Department of Mechanical and Aerospace Engineering, Princeton University, Olden Street, Princeton, NJ 08544, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Engineering Quad, Department of Mechanical and Aerospace Engineering, Princeton University, Olden Street, Princeton, NJ 08544, USA.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Stone
authors.affiliation: Lewis Thomas Laboratory, Department of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USA. Electronic address: zgitai@princeton.edu.
authors.forename: Zemer
authors.initials: Z
authors.lastname: Gitai
mesh_terms: D018407:Bacterial Physiological Phenomena; D057446:Hydrodynamics; D010935:Plant Diseases / Q000382:microbiology; D058526:Plant Vascular Bundle / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D014026:Nicotiana
references.citation: JAMA. 1995 Aug 23-30;274(8):639-44
references.pmid: 7637145
references.citation: Microbes Infect. 2000 Oct;2(12):1497-505
references.pmid: 11099936
references.citation: Elife. 2014 May 27;3:e02403
references.pmid: 24867640
references.citation: Biophys J. 2012 Jul 3;103(1):146-51
references.pmid: 22828341
references.citation: J Bacteriol. 2005 Aug;187(16):5560-7
references.pmid: 16077100
references.citation: Annu Rev Biochem. 2003;72:19-54
references.pmid: 12500982
references.citation: J Pediatr. 2009 Feb;154(2):183-8
references.pmid: 18822427
references.citation: Science. 1983 Nov 4;222(4623):500-1
references.pmid: 17746198
references.citation: Rev Infect Dis. 1983 Mar-Apr;5(2):279-313
references.pmid: 6405475
references.citation: Stroke. 1984 Jan-Feb;15(1):50-6
references.pmid: 6695430
references.citation: Cell. 2007 Jul 27;130(2):335-47
references.pmid: 17662947
references.citation: Plant Physiol. 1966 Jan;41(1):119-31
references.pmid: 16656221
references.citation: Cell Host Microbe. 2010 Sep 16;8(3):292-300
references.pmid: 20833380
references.citation: J Bacteriol. 2013 Jan;195(2):368-77
references.pmid: 23144253
references.citation: Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16860-5
references.pmid: 25385640
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4780-5
references.pmid: 22411815
references.citation: Phys Rev Lett. 2007 Feb 9;98(6):068101
references.pmid: 17358984
references.citation: Annu Rev Microbiol. 2002;56:289-314
references.pmid: 12142488
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12617-22
references.pmid: 21768344
references.citation: J Med Microbiol. 2011 Feb;60(Pt 2):236-245
references.pmid: 20947663
references.citation: J Gen Physiol. 1988 May;91(5):725-35
references.pmid: 3418319
references.citation: Nat Rev Microbiol. 2010 Jan;8(1):15-25
references.pmid: 19946288
references.citation: Eur J Clin Microbiol Infect Dis. 2001 Mar;20(3):188-91
references.pmid: 11347669
references.citation: Am J Med. 2002 Jul 8;113 Suppl 1A:14S-19S
references.pmid: 12113867