Pharmacodynamics of ciprofloxacin againstPseudomonas aeruginosaplanktonic and biofilm‐derived cells

Abstract

Significance and Impact of the Study: Removal of biofilms from surfaces and infection sites via disaggregation and induction of dispersion may reverse their antibiotic tolerant state. However, little is known of the recovery of the cells upon disaggregation from biofilms. Driven by this gap in knowledge we quantified the effect of ciprofloxacin on disaggregated biofilms of Pseudomonas aeruginosa, including those previously exposed to ciprofloxacin. Our results provide further insight into bacterial resilience, regrowth, and antimicrobial efficacy, as reduction in cell viability does not directly correlate with the metabolic activity of bacteria at the time of the exposure to antimicrobials. Thus, despite a perceived reduction in viability, the potential for cell persistence and regrowth remains and recovery is quicker upon subsequent exposure to antimicrobial, supporting the increase in resilience and recurrence of infections. AbstractThe influence of growth phase and state on the survival and recovery of Pseudomonas aeruginosa exposed to ciprofloxacin was investigated using batch culture grown planktonic cells and disaggregated biofilm populations. Biofilms were either nonantibiotic exposed or previously exposed to ciprofloxacin before disaggregation and subsequent challenge with ciprofloxacin. Viable counts showed that late stationary phase cells were tolerant to ciprofloxacin over 24 h exposure, while all other populations presented a biphasic killing pattern. In contrast, the metabolic activity of planktonic and biofilm-derived cells remained similar to controls during the initial 6 h of ciprofloxacin exposure, despite a significant reduction in viable cell numbers. A similar effect was observed when assessing the postantibiotic effect of 1 h ciprofloxacin exposure. Thus, although cell reduction occurred, the metabolic status of the cells remained unchanged. The recovery of disaggregated biofilm cells previously exposed to ciprofloxacin was significantly quicker than na€ ıve biofilm cells, and this latter population's recovery was significantly slower than all planktonic populations. Results from this work have implications for our understanding of biofilm-related infections and their resilience to antimicrobial treatment.

Small Molecule Inhibitors of the Bacterioferritin (BfrB)–Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells

“…The perceived reduction in viable cell counts, which did not correlate with the relatively high metabolic activity reported by the small decrease in bioluminescence, indicated that challenges with ciprofloxacin induce P. aeruginosa cells to enter a VBNC state. 61,62 Our observations suggest a similar situation. Imaging the pellicles with CLSM following the 24 h challenge with ciprofloxacin (Figure 7B,C) shows that most of the cells are metabolically active (yellow fluorescent), but dispersion of the cells from the pellicles for enumeration of CFU/mL shows a large reduction in culturable cells relative to the untreated control.…”

Adaptive response of Pseudomonas aeruginosa under serial ciprofloxacin exposure

“…Besides the presence of long filaments, reduced cell length and width in response to ciprofloxacin were also seen in this study. This observation was previously reported in a biofilm population of P. aeruginosa exposed to ciprofloxacin for 24 h [23] and also in P. aeruginosa exposed to carbapenem [24].…”

A Novel Non-Coding RNA CsiR Regulates the Ciprofloxacin Resistance in Proteus vulgaris by Interacting with emrB mRNA

“…Studies have obtained strong evidence that antibiotics are the direct driving force behind bacterial resistance. As part of the third generation of synthetic quinolone antibacterial drugs, ciprofloxacin is widely used in clinical treatment and agricultural cultivation, inhibiting the normal function of bacterial DNA helicase and causing irreversible damage, leading to good antibacterial effects on Pseudomonas aeruginosa , Escherichia coli , Proteus vulgaris , and many other Enterobacteriaceae bacteria [ 38 , 39 , 40 , 41 , 42 ]. We previously isolated a multidrug-resistant P. vulgaris strain P3M from the intestinal tract of Penaeus vannamei, with 67 ncRNAs being identified [ 30 ].…”