Sulfated vizantin suppresses mucin layer penetration dependent on the flagella motility of Pseudomonas aeruginosa PAO1

PLoS One. 2018 Nov 1;13(11):e0206696. doi: 10.1371/journal.pone.0206696. eCollection 2018.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections, such as pneumonia and bacteremia. Several studies demonstrated that flagellar motility is an important virulence factor for P. aeruginosa infection. In this study, we determined whether sulfated vizantin affects P. aeruginosa flagellar motility in the absence of direct antimicrobial activity. We found that 100 μM sulfated vizantin suppressed P. aeruginosa PAO1 from penetrating through an artificial mucin layer by affecting flagellar motility, although it did not influence growth nor bacterial protease activity. To further clarify the mechanism in which sulfated vizantin suppresses the flagellar motility of P. aeruginosa PAO1, we examined the effects of sulfated vizantin on the composition of the flagellar filament and mRNA expression of several flagella-related genes, finding that sulfated vizantin did not influence the composition of the flagellar complex (fliC, motA, and motB) in P. aeruginosa PAO1, but significantly decreased mRNA expression of the chemotaxis-related genes cheR1, cheW, and cheZ. These results indicated that sulfated vizantin is an effective inhibitor of flagellar motility in P. aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism
  • Flagella / drug effects*
  • Flagella / physiology
  • Flagella / ultrastructure
  • Gene Expression / drug effects
  • Glycolipids / pharmacology*
  • Movement / drug effects
  • Movement / physiology
  • Mucins* / drug effects
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / physiology
  • Pseudomonas aeruginosa / ultrastructure
  • RNA, Messenger / metabolism
  • Serine Endopeptidases / metabolism
  • Trehalose / analogs & derivatives*
  • Trehalose / pharmacology

Substances

  • 6,6'-bis-O-(3-nonyldodecanoyl)-alpha,alpha'-trehalose
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Glycolipids
  • Mucins
  • RNA, Messenger
  • Trehalose
  • Pseudomonas serine proteinase
  • Serine Endopeptidases

Grants and funding

This research was funded by the Japan society for the promotion of science (JSPS) KAKENHI Grant Numbers 18H02657 and 15H05017 suppported to MO, https://www.jsps.go.jp/english/index.html; JSPS KAKENHI Grant Numbers 16K19129 and 26860295 supported to NH, https://www.jsps.go.jp/english/index.html; Ministry of Education, Culture, Sports, Science and Technology (MEXT) Supported Program for the Strategic Research Foundation at Private Universities, Japan, 2013–2017 supported to MO, http://www.mext.go.jp/a_menu/koutou/shinkou/07021403/002/002/1218299.htm; Takeda Science Foundation supported to MO, http://www.takeda-sci.or.jp/business/abroad_e.html; and Kyoto Pharmaceutical University Fund for the Promotion of Scientific Research supported to NH, https://www.kyoto-phu.ac.jp/english/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.