4.6 Article

Lipopolysaccharide structure modulates cationic biocide susceptibility and crystalline biofilm formation in Proteus mirabilis

Journal

FRONTIERS IN MICROBIOLOGY
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2023.1150625

Keywords

Proteus mirabilis; biocide; biofilm; lipopolysaccharide; catheter associated urinary tract infection; biocide resistance; antimicrobials; AMR

Categories

Ask authors/readers for more resources

Chlorhexidine (CHD), a commonly used biocide in healthcare settings, is often considered ineffective against Proteus mirabilis in catheter infection control. This study investigated the mechanisms of reduced CHD susceptibility in P. mirabilis and found that a mutation in the waaC gene, involved in lipopolysaccharide (LPS) biosynthesis, resulted in decreased CHD minimum inhibitory concentrations (MICs). The mutation also increased cell surface hydrophobicity and susceptibility to other cationic biocides. Additionally, repression of the smvA efflux system further enhanced CHD susceptibility. These findings highlight the importance of LPS structure and the smvA efflux system in modulating susceptibility to CHD and other biocides in P. mirabilis.
Chlorhexidine (CHD) is a cationic biocide used ubiquitously in healthcare settings. Proteus mirabilis, an important pathogen of the catheterized urinary tract, and isolates of this species are often described as resistant to CHD-containing products used for catheter infection control. To identify the mechanisms underlying reduced CHD susceptibility in P. mirabilis, we subjected the CHD tolerant clinical isolate RS47 to random transposon mutagenesis and screened for mutants with reduced CHD minimum inhibitory concentrations (MICs). One mutant recovered from these screens (designated RS47-2) exhibited similar to 8-fold reduction in CHD MIC. Complete genome sequencing of RS47-2 showed a single mini-Tn5 insert in the waaC gene involved in lipopolysaccharide (LPS) inner core biosynthesis. Phenotypic screening of RS47-2 revealed a significant increase in cell surface hydrophobicity and serum susceptibility compared to the wildtype, and confirmed defects in LPS production congruent with waaC inactivation. Disruption of waaC was also associated with increased susceptibility to a range of other cationic biocides but did not affect susceptibility to antibiotics tested. Complementation studies showed that repression of smvA efflux activity in RS47-2 further increased susceptibility to CHD and other cationic biocides, reducing CHD MICs to values comparable with the most CHD susceptible isolates characterized. The formation of crystalline biofilms and blockage of urethral catheters was also significantly attenuated in RS47-2. Taken together, these data show that aspects of LPS structure and upregulation of the smvA efflux system function in synergy to modulate susceptibility to CHD and other cationic biocides, and that LPS structure is also an important factor in P. mirabilis crystalline biofilm formation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available