In Vitro Efficacy of Free and Nanoparticle Formulations of Gallium(III) meso-Tetraphenylporphyrine against Mycobacterium avium and Mycobacterium abscessus and Gallium Biodistribution in Mice

Choi, Seoung Ryoung; Britigan, Bradley E.; Switzer, Barbara L.; Hoke, Traci; Moran, D.M.; Narayanasamy, Prabagaran

doi:10.1021/acs.molpharmaceut.7b01036

Cited by 30 publications

(57 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous works demonstrated that macrophage-targeted Ga(III) nanoparticles have a prolonged antimicrobial effect against Mycobacterium abscessus, Mycobacterium avium, Mycobacterium tuberculosis, and Mycobacterium smegmatis within macrophages because of sustained Ga(III) release over time (27)(28)(29)39). In the current work, we found that THP-1 cells preloaded with GaMP, CDGaPP, or eFGaMP exhibited resistance to P. aeruginosa infection, but only for 3 days, losing all activity at day 5 postloading.…”

Section: Discussionmentioning

confidence: 47%

Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii

Choi

Britigan

Narayanasamy

2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Iron/heme acquisition systems are critical for microorganisms to acquire iron from the human host, where iron sources are limited due to the nutritional immune system and insolubility of the ferric form of iron. Prior work has shown that a variety of gallium compounds can interfere with bacterial iron acquisition. This study explored the intra-and extracellular antimicrobial activities of gallium protoporphyrin (GaPP), gallium mesoporphyrin (GaMP), and nanoparticles encapsulating GaPP or GaMP against the Gram-negative pathogens Pseudomonas aeruginosa and Acinetobacter baumannii, including clinical isolates. All P. aeruginosa and A. baumannii isolates were susceptible to GaPP and GaMP, with MICs ranging from 0.5 to ϳ32 g/ml in iron-depleted medium. Significant intra-and extracellular growth inhibition was observed against P. aeruginosa cultured in macrophages at a gallium concentration of 3.3 g/ml (5 M) of all Ga(III) compounds, including nanoparticles. Nanoparticle formulations showed prolonged activity against both P. aeruginosa and A. baumannii in previously infected macrophages. When the macrophages were loaded with the nanoparticles 3 days prior to infection, there was a 5-fold decrease in growth of P. aeruginosa in the presence of single emulsion F127 copolymer nanoparticles encapsulating GaMP (eFGaMP). In addition, all Ga(III) porphyrins and nanoparticles showed significant intracellular and antibiofilm activity against both pathogens, with the nanoparticles exhibiting intracellular activity for 3 days. Ga nanoparticles also increased the survival rate of Caenorhabditis elegans nematodes infected by P. aeruginosa and A. baumannii. Our results demonstrate that Ga nanoparticles have prolonged in vitro and in vivo activities against both P. aeruginosa and A. baumannii, including disruption of their biofilms.

show abstract

Section: Discussionmentioning

confidence: 47%

Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii

Choi

Britigan

Narayanasamy

2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…We also demonstrated that long-acting Ga nanoparticles (GaNP) inhibited the growth of both HIV and the attenuated H37Ra strain of M. tuberculosis during coinfection within human monocyte-derived macrophages (MDMs) in vitro (19–21). Treatment of the HIV-H37Ra coinfected macrophages by GaNP reduced the secretion of IL-6 and IL-8 for up to 15 days.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies done by us and other research groups demonstrated that gallium disrupts iron acquisition by intracellular mycobacteria and Gram-positive and Gram-negative bacteria (11, 15, 16). Macrophage-targeted (mannose-tagged) nanoparticles have been developed to increase drug delivery to macrophages and demonstrated significant growth inhibition of mycobacteria relative to untreated controls (17–19). We also demonstrated that long-acting Ga nanoparticles (GaNP) inhibited the growth of both HIV and the attenuated H37Ra strain of M.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Virulent Mycobacterium tuberculosis and HIV Coinfected Macrophages with Gallium Nanoparticles Inhibits Pathogen Growth and Modulates Macrophage Cytokine Production

Choi

Britigan

Narayanasamy

2019

mSphere

Self Cite

View full text Add to dashboard Cite

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a global threat. The course of TB is negatively impacted by coexistent infection with human immunodeficiency virus type 1 (HIV). Macrophage infection with these pathogens modulates their production of pro- and anti-inflammatory cytokines, which could play a crucial role in pathogenesis. Despite the important role of macrophages in containing infection by a variety of microbes, both HIV and M. tuberculosis infect and replicate within these cells during the course of HIV-M. tuberculosis coinfection. Both M. tuberculosis and HIV require iron for growth and replication. We have previously shown that gallium encapsulated in nanoparticles, which interferes with cellular iron acquisition and utilization, inhibited the growth of HIV and an attenuated strain of M. tuberculosis within human monocyte-derived macrophages (MDMs) in vitro. Whether this was true for a fully virulent strain of M. tuberculosis and whether gallium treatment modulates cytokine production by HIV- and/or M. tuberculosis-infected macrophages have not been previously addressed. Therefore, coinfection of MDMs with HIV and a virulent M. tuberculosis strain (H37Rv) was studied in the presence of different gallium nanoparticles (GaNP). All GaNP were readily internalized by the MDMs, which provided sustained drug (gallium) release for 15 days. This led to significant growth inhibition of both HIV and M. tuberculosis within MDMs for up to 15 days after loading of the cells with all GaNP tested in our study. Cytokine analysis showed that HIV-M. tuberculosis coinfected macrophages secreted large amounts of interleukin 6 (IL-6) and IL-8 and smaller amounts of IL-1β, IL-4, and tumor necrosis factor alpha (TNF-α) cytokines. However, all GaNP were able to regulate the release of cytokines significantly. GaNP interrupts iron-mediated enzymatic reactions, leading to growth inhibition of HIV-M. tuberculosis coinfection in macrophages, and also modulates release of cytokines that may contribute to HIV-TB pathogenesis. IMPORTANCE GaNP interrupts iron-mediated enzymatic reactions, leading to growth inhibition of virulent HIV-M. tuberculosis coinfection in macrophages, and also modulates release of cytokines that may contribute to HIV-TB pathogenesis. Macrophage-targeting GaNP are a promising therapeutic approach to provide sustained antimicrobial activity against HIV-M. tuberculosis coinfection.

show abstract

“…As highlighted in Table 3 , intracellular DSTs can differ in selected cell types and experimental procedures. The human monocytic cell lines THP-1 and U937 are commonly used to screen antimicrobial molecules and investigate dose-response against intracellular NTM [ 26 , 27 , 28 , 29 , 30 ]. These cells are differentiated by phorbol 12-myristate 13-acetate (PMA) to mimic the morphology and functions of mature macrophages.…”

Section: Static Intracellular Infection Modelsmentioning

confidence: 99%

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

et al. 2020

View full text Add to dashboard Cite

Nontuberculous mycobacteria (NTM) represent an increasingly prevalent etiology of soft tissue infections in animals and humans. NTM are widely distributed in the environment and while, for the most part, they behave as saprophytic organisms, in certain situations, they can be pathogenic, so much so that the incidence of NTM infections has surpassed that of Mycobacterium tuberculosis in developed countries. As a result, a growing body of the literature has focused attention on the critical role that drug susceptibility tests and infection models play in the design of appropriate therapeutic strategies against NTM diseases. This paper is an overview of the in vitro and in vivo models of NTM infection employed in the preclinical phase for early drug discovery and vaccine development. It summarizes alternative methods, not fully explored, for the characterization of anti-mycobacterial compounds.

show abstract

In Vitro Efficacy of Free and Nanoparticle Formulations of Gallium(III) meso-Tetraphenylporphyrine against Mycobacterium avium and Mycobacterium abscessus and Gallium Biodistribution in Mice

Cited by 30 publications

References 49 publications

Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii

Iron/Heme Metabolism-Targeted Gallium(III) Nanoparticles Are Active against Extracellular and Intracellular Pseudomonas aeruginosa and Acinetobacter baumannii

Treatment of Virulent Mycobacterium tuberculosis and HIV Coinfected Macrophages with Gallium Nanoparticles Inhibits Pathogen Growth and Modulates Macrophage Cytokine Production

Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research

Contact Info

Product

Resources

About