Quinine Enhances Photo-Inactivation of Gram-Negative Bacteria

Leanse, Leon G.; Dong, Pu‐Ting; Goh, Xueping Sharon; Lü, Min; Cheng, Ji‐Xin; Hooper, David C.

doi:10.1093/infdis/jiz487

Cited by 26 publications

(25 citation statements)

References 25 publications

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“…1A and 3C). 305 Recently, studies of photodynamic therapy (PDT) have revealed light, simultaneously applied with antibiotics, as a potentiator of biofilm infection eradication (49)(50)(51). Our finding that PYO, also classified as an antibiotic (52), in conjunction with light diminishes biofilm integrity is consistent with the notion that an oxidizing environment, which is often created as a result of antibiotic treatment, and light together enhance remediation of biofilm-based infections.…”

Section: Phosphodiesterases (Pdes) Contribute To the Light-dependent supporting

confidence: 79%

Light-mediated decreases in cyclic di-GMP levels are potentiated by pyocyanin and inhibit structure formation inPseudomonas aeruginosabiofilms

Kahl¹,

Price-Whelan²,

Dietrich³

2019

Preprint

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25Light is known to trigger regulatory responses in diverse organisms including slime molds, animals, plants, and phototrophic bacteria. However, light-dependent processes in nonphototrophic bacteria, and those of pathogens in particular, have received comparatively little research attention. In this study, we examined the impact of light on multicellular development in Pseudomonas aeruginosa, a leading cause of biofilm-based bacterial 30 infections, using a colony morphology assay. In this assay, P. aeruginosa strain PA14 grown in the dark forms vertical structures (i.e., "wrinkles") on the third day of incubation.We found that growth in blue light inhibited wrinkle formation until the fifth day and that this required the phenazine pyocyanin, a redox-active metabolite produced by PA14.Light-dependent inhibition of wrinkling was also correlated with low levels of cyclic di-35 GMP (c-di-GMP), consistent with the role of this signal in stimulating biofilm matrix production. Though phenazine-null biofilms also showed lower levels of c-di-GMP and subtle effects on wrinkling when grown in the light, their overall levels of c-di-GMP were higher than those of the wild type. This indicates that phenazines and light simultaneously promote c-di-GMP degradation such that c-di-GMP is pushed to a minimum level, yielding 40 a pronounced macroscopic phenotype. A screen of enzymes with the potential to catalyze c-di-GMP synthesis or degradation identified four proteins that contribute to lightdependent inhibition of biofilm wrinkling. Together, these results provide a foundation for understanding the significance of light-dependent regulation in P. aeruginosa.3 Importance 45 The response to light in non-phototrophic bacteria (i.e., chemotrophs) is relatively understudied in comparison to light-mediated behavior in eukaryotes and phototrophic bacteria. Though they do not depend on light for growth, chemotrophic bacteria could benefit from sensing this cue when it correlates with other parameters that are important for metabolism. In this paper, we describe light-dependent effects on a cellular signal that 50 controls the development of multicellular assemblages, called biofilms, in Pseudomonas aeruginosa. We found that light at intensities that are not harmful to human cells inhibited biofilm maturation. P. aeruginosa is a leading cause of chronic lung infections in people with cystic fibrosis and of hospital-acquired infections. As P. aeruginosa's recalcitrance to treatment is attributed in part to its facile formation of biofilms, this study provides 55 insight into a mechanism that could be inhibited via new therapeutic tools, such as photodynamic therapy. 75 light inhibits exopolysaccharide excretion, biofilm development, and virulence via a bacteriophytochrome that binds a bilin cofactor (3). In Caulobacter crescentus, Bacillus subtilis, and Brucella abortus, photosensory proteins link the effects of blue light on FMN cofactors to regulation of adhesion, the general stress response, and pathogenicity (4-6). Furthermore...

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Section: Phosphodiesterases (Pdes) Contribute To the Light-dependent supporting

confidence: 79%

Light-mediated decreases in cyclic di-GMP levels are potentiated by pyocyanin and inhibit structure formation inPseudomonas aeruginosabiofilms

Kahl¹,

Price-Whelan²,

Dietrich³

2019

Preprint

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“…During aBL irradiation, the bacterial suspension was stirred using a 12-mm magnetic bar (20 rpm) to prevent sedimentation. A total of four aliquots of aBL were delivered (27, 54, 81 and 108 J/cm 2 ) and 30 µL of the suspension was withdrawn following each aliquot to determine the CFU as described previously (19). Experiments were performed in triplicate.…”

Section: Abl+q-hcl Inactivation Of Planktonic C Albicans In Vitromentioning

confidence: 99%

“…Quinine is a potent antimalarial compound that has been shown to have inherent antibacterial and antifungal properties, albeit at high concentrations (16)(17)(18). In a previous study, we found Q-HCL to significantly enhance the effects of aBL in Gram-negative bacteria (19), Therefore, in this study we investigated the combined use of aBL and quinine hydrochloride for the inactivation of C. albicans, both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Quinine Improves the Fungicidal Effects of Antimicrobial Blue Light: Implications for the Treatment of Cutaneous Candidiasis

Leanse

Goh

2019

Lasers Surg Med

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Background. Candida albicans is an opportunistic fungal pathogen of clinical importance and is the primary cause of fungal-associated wound infections, sepsis or pneumonia in immunocompromised individuals. With the rise in antimicrobial resistance, it is becoming increasingly difficult to successfully treat fungal infections using traditional antifungals, signifying that alternative nontraditional approaches must be explored for their efficacy.Methods. We investigated the combination of antimicrobial blue light (aBL) and quinine hydrochloride (Q-HCL) for improved inactivation of C. albicans, in vitro and in vivo, relative to either monotherapy. In addition, we evaluated the safety of this combination therapy in vivo using the TUNEL assay.Results. The combination of aBL (108 J/cm 2 ) with Q-HCL (1 mg/mL) resulted in a significant improvement in the inactivation of C. albicans planktonic cells in vitro, where 7.04 log 10 CFU reduction was achieved, compared with aBL alone that only inactivated 3.06 log 10 CFU (P<0.001). aBL+Q-HCL was also effective at inactivating 48-hour biofilms, with an inactivation 1.73 log 10 CFU at the dose of 108 J/cm 2 aBL and 1 mg/mL Q-HCL, compared with only a 0.73 or 0.66 log 10 CFU by aBL and Q-HCL alone, respectively (P<0.001). Transmission electron microscopy revealed that aBL+Q-HCL induced morphological and ultrastructural changes consistent with cell wall and cytoplasmic damage. In addition, aBL+Q-HCL was effective at eliminating C. albicans within mouse abrasion wounds, with a 2.47 log 10 relative luminescence unit (RLU) reduction at the dose of 324 J/cm 2

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“…Confronted with this dire situation, antimicrobial blue light has emerged as a novel approach to combat multidrug-resistant bacterial infections 5,6 . Blue light in the 405-420 nm or the 450-470 nm optical windows has demonstrated bactericidal effects towards a wide range of microbial species, including gram-positive bacteria, gram-negative bacteria, mycobacteria, and molds 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Blue light has also been allied with other antimicrobial agents to eradicate bacteria. For example, quinine in combination with blue light exposure has shown efficacy to eliminate gram-negative P. aeruginosa, Acinetobacter baumannii ( A. baumannii ) 5 and Candida albicans 14 . Blue light irradiance was also reported to enhance the inactivation efficacy of low-concentration chlorinated disinfectants towards Clostridium difficile 15 .…”

Section: Introductionmentioning

confidence: 99%

Photoinactivation of Catalase Sensitizes Wide-Ranging Bacteria to ROS-Producing Agents and Immune Cells

Dong

Jusuf

Hui

et al. 2021

Preprint

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Bacteria have evolved to cope with the detrimental effects of reactive oxygen species (ROS) using their essential molecular components. Catalase, a heme-containing tetramer protein expressed universally in most of the aerobic bacteria, plays an indispensable role in scavenging excess hydrogen peroxide (H2O2). Here, through utilization of wild-type and catalase-deficient mutants, we identified catalase as an endogenous therapeutic target of 400-420 nm blue light. Catalase residing in bacteria could be effectively inactivated by blue light, subsequently rendering the pathogens extremely vulnerable to H2O2 and H2O2-producing agents. As a result, photoinactivation of catalase and H2O2 synergistically eliminate a wide range of catalase-positive planktonic bacteria and P. aeruginosa inside biofilms. In addition, photoinactivation of catalase is shown to facilitate macrophages to defend against intracellular pathogens. The antimicrobial efficacy of catalase photoinactivation is further validated using a Pseudomonas aeruginosa-induced mice abrasion model. Taken together, our findings offer a catalase-targeting phototherapy against multidrug-resistant bacterial infections.

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Quinine Enhances Photo-Inactivation of Gram-Negative Bacteria

Cited by 26 publications

References 25 publications

Light-mediated decreases in cyclic di-GMP levels are potentiated by pyocyanin and inhibit structure formation inPseudomonas aeruginosabiofilms

Light-mediated decreases in cyclic di-GMP levels are potentiated by pyocyanin and inhibit structure formation inPseudomonas aeruginosabiofilms

Quinine Improves the Fungicidal Effects of Antimicrobial Blue Light: Implications for the Treatment of Cutaneous Candidiasis

Photoinactivation of Catalase Sensitizes Wide-Ranging Bacteria to ROS-Producing Agents and Immune Cells

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