Pseudomonas aeruginosa PAO1 Resistance to Zinc Pyrithione: Phenotypic Changes Suggest the Involvement of Efflux Pumps

Abstract

The aim of this study is to investigate the involvement of an efflux pump in the development of Pseudomonas aeruginosa resistance to zinc pyrithione (ZnPT). In the presence of efflux inhibitor carbonyl cyanide m-chlorophenyl-hydrazone (CCCP), the minimum inhibitory concentration of ZnPT for P. aeruginosa resistant cells is reduced significantly (p \ 0.05). In addition, the concentration of ZnPT excluded by the resistant bacteria was reduced significantly (p \ 0.01). However, the above reductions did not reach the levels measured for P. aeruginosa PAO1 sensitive strain. Furthermore, such changes in P. aeruginosa resistant cells were correlated with the overexpression of outer membrane proteins, reduced sensitivity toward imipenem (p \ 0.01) and increased sensitivity toward sulphatriad and chloramphenicol (p \ 0.05). In a continuation to a previous study, we conclude that P. aeruginosa resistance to ZnPT is multifactorial and involves induced efflux systems.

Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment

“…Considering that one of our overarching goals was to identify novel therapeutics for the treatment of wound-associated bacterial infections, we considered that zinc pyrithione (ZnPT) may be a viable topical candidate to explore further because (i) ZnPT is currently a successful topical treatment of seborrheic dermatitis with a favorable safety profile ( 25 ), (ii) bacterial ZnPT resistance is slow to develop and unlikely to confer cross-resistance to systemic antibiotics ( 26 ), and (iii) ZnPT has been previously shown to have excellent antibiofilm activity toward A. baumannii , another common wound infection-associated organism ( 27 ).…”

A Novel Approach To Identify Inhibitors of Iron Acquisition Systems of Pseudomonas aeruginosa

“…An unexpected finding of our HTS assay was the observation that tannic acid (TA) and zinc pyrithione (ZPT) inhibited the growth of P. aeruginosa in the presence of both FeCl 3 and Hm. Previous studies have shown that these molecules can be potent inhibitors of P. aeruginosa during both planktonic and biofilm growth ( 47 , 48 ). Since TA and ZPT are known metal-chelating compounds ( 49 , 50 ), it is likely that they inhibit P. aeruginosa growth in FeCl 3 through ferric iron chelation.…”

Turning on the Antimicrobial Activity of Gold Nanoclusters Against Multidrug‐Resistant Bacteria**

“…[49] P. aeruginosa has also developed systems for maintaining metal homeostasis, including metallo-responsive proteins and dedicated metal-pumping efflux channels. [50] To evaluate whether AuNC-Mal/TU is affected by the efflux, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), which disrupts the proton gradient required for bacteria efflux of metals and antibiotics, [51,52] was added and the Au concentration in P. aeruginosa treated with AuNC-Mal/TU was measured. Addition of CCCP did not result in a significant increase in Au concentration, implying that the accumulation is independent of efflux (Figure S32).…”