Chlorhexidine promotes psl in Pseudomonas aeruginosa that enhances cell aggregation with preserved pathogenicity demonstrates an adaptation against antiseptic

ABSTRACT: Because Pseudomonas aeruginosa is a common pathogen that frequently contacts with Chlorhexidine digluconate (a regular antiseptic), then adaptations against Chlorhexidine were tested. In com-parison with the parent strain, the Chlorhexidine-adapted strain formed smaller colonies with the downregulation of several metabolic pathways (proteomic analysis) and increased resistance against colistin (an antibiotic for the current antibiotic-resistant bacteria), partly through the modification of L-Ara4N in the lipopolysaccharide at the outer membrane (proteomic analysis). Chlorhexidine-adapted strain formed dense liquid-solid interface biofilm with cell aggregation partly due to the Chlorhexidine-induced overexpression of psl (exopolysaccharide-encoded gene) through LadS/GacSA pathway (c-di-GMP-independence) in 12 h biofilms and maintained the ag-gregation with SiaD-mediated c-di-GMP dependence in 24 h biofilms as evaluated by polymerase chain reaction (PCR). The addition of Ca2+ in the Chlorhexidine-adapted strain facilitated several Psl-associated genes, indicating an impact of Ca2+ in Psl production. The sessile Chlorhexi-dine-treated bacteria demonstrated a lower expression of IL-6 and IL-8 on fibroblasts and mac-rophages than the parent strain, indicating less inflammatory reactions from the Chlorhexidine use. However, the Chlorhexidine-treated bacteria induces similar severity in 14 days of mouse wounds as indicated by wound score and bacterial burdens. In conclusion, Chlorhexidine induced psl over-expression and colistin cross-resistance that might be clinically important.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jiradej Makjaroen  

LAB HEAD: Asada Leelahavanichkul

PROVIDER: PXD034530 | Pride | 2022-10-14

REPOSITORIES: Pride