Human tear fluid modulates the Pseudomonas aeruginosa transcriptome to alter antibiotic susceptibility.

Ocul Surf

School of Optometry, University of California, Berkeley, CA, USA; Graduate Groups in Vision Science, Microbiology, and Infectious Diseases & Immunity, University of California, Berkeley, CA, USA. Electronic address:

Published: October 2021

AI Article Synopsis

  • Tear fluid was shown to impact the gene expression of Pseudomonas aeruginosa, regulating around 180 genes, including those related to virulence and antibiotic resistance.
  • The study utilized RNA-sequencing and other methods to explore how tear fluid exposure affected bacterial behavior and response to antibiotics.
  • Results indicated that while tear fluid made P. aeruginosa more resistant to certain antibiotics, it significantly increased sensitivity to polymyxin B, highlighting its complex role in bacterial adaptation.

Article Abstract

Purpose: Previously, we showed that tear fluid protects corneal epithelial cells against Pseudomonas aeruginosa without suppressing bacterial viability. Here, we studied how tear fluid affects bacterial gene expression.

Methods: RNA-sequencing was used to study the P. aeruginosa transcriptome after tear fluid exposure (5 h, 37 C). Outcomes were further investigated by biochemical and physiological perturbations to tear fluid and tear-like fluid (TLF) and assessment of bacterial viability following tear/TLF pretreatment and antibiotic exposure.

Results: Tear fluid deregulated ~180 P. aeruginosa genes ≥8 fold versus PBS including downregulating lasI, rhlI, qscR (quorum sensing/virulence), oprH, phoP, phoQ (antimicrobial resistance) and arnBCADTEF (polymyxin B resistance). Upregulated genes included algF (biofilm formation) and hemO (iron acquisition). qPCR confirmed tear down-regulation of oprH, phoP and phoQ. Tear fluid pre-treatment increased P. aeruginosa resistance to meropenem ~5-fold (4 μg/ml), but enhanced polymyxin B susceptibility ~180-fold (1 μg/ml), the latter activity reduced by dilution in PBS. Media containing a subset of tear components (TLF) also sensitized bacteria to polymyxin B, but only ~22.5-fold, correlating with TLF/tear fluid Ca and Mg concentrations. Accordingly, phoQ mutants were not sensitized by TLF or tear fluid. Superior activity of tear fluid versus TLF against wild-type P. aeruginosa was heat resistant but proteinase K sensitive.

Conclusion: P. aeruginosa responds to human tear fluid by upregulating genes associated with bacterial survival and adaptation. Meanwhile, tear fluid down-regulates multiple virulence-associated genes. Tears also utilize divalent cations and heat resistant/proteinase K sensitive component(s) to enhance P. aeruginosa sensitivity to polymyxin B.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139757PMC
http://dx.doi.org/10.1016/j.jtos.2021.07.004DOI Listing

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