FFC#21/2019

Preclinical study of a combined host- and pathogen directed approach based on bioactive liposomes and bacteriophages against Mycobacterium abscessus infection

FFC#21/2019

Preclinical study of a combined host- and pathogen directed approach based on bioactive liposomes and bacteriophages against Mycobacterium abscessus infection

PRINCIPAL INVESTIGATOR

Maurizio Fraziano (Dip. Biologia, Università Tor Vergata, Roma)

RESEARCHERS

7

CATEGORY

AREA 4 Lung inflammation

DURATION

2 years

GOAL

€ 120.000 €

RESULTS

The researchers evaluated the efficacy in vivo and in vitro of a novel combined host- and pathogen- directed therapeutic approach, based on bioactive liposomes (host-directed therapy, HDT) and phages (pathogen-directed therapy, PDT) against Mycobacterium abscessus (Mab). As the identification of Mab specific phages did not result in potential phage candidates so far, the therapeutic value of the combined strategy was assessed by using the antibiotic amikacin (AMK) as PDT. The results show that liposome-based HDT enhances antimycobacterial response, in infection models i) in vitro on macrophages from CF patients and ii) in in vivo on CF mice, where it induces a significant decrease of leucocyte recruitment and a reduction of about 200-fold of pulmonary mycobacterial burden. Such microbicidal and anti-inflammatory action is further enhanced in the presence of the combined treatment with AMK. The results obtained by the researchers offer the basis for the development of a new combined therapeutic regimen based on bioactive liposomes and antibiotics, which can be used against Mab infections in patients with CF.

Pubblications

  • De Santis F., Borrajo López A., Virtuoso S. et al., Phosphatidylcholine liposomes down-modulate CD4 expression reducing HIV entry in human type-1 macrophages, Frontiers in immunology  vol. 13 830788. 19 May. 2022
  • Poerio N, Olimpieri T, Henrici De Angelis L et al., Fighting MDR-Klebsiella pneumoniae Infections by a Combined Host- and Pathogen-Directed Therapeutic Approach, Frontiers in immunology vol. 13 835417. 14 Feb. 2022
  • Poerio N, Riva C, Olimpieri T et al., Combined Host- and Pathogen-Directed Therapy for the Control of Mycobacterium abscessus Infection, Microbiology spectrum vol. 10,1 (2022): e0254621
  • Rinaldi F, Hanieh PN, Sennato S et al., Rifampicin-Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation, Pharmaceutics vol. 13,7 1070. 13 Jul. 2021
  • Grassi G, Vanini V, De Santis F et al., PMN-MDSC Frequency Discriminates Active Versus Latent Tuberculosis and Could Play a Role in Counteracting the Immune-Mediated Lung Damage in Active Disease, Frontiers in immunology vol. 12 594376. 26 Apr. 2021
  • Nisini R, Oggioni MR, Rossolini GM, Fraziano M. Editorial: Exploiting Novel Combined Host- and Pathogen-Directed Therapies for Combating Bacterial Multidrug Resistance, Frontiers in immunology vol. 11 616486. 4 Nov. 2020
  • Poerio N, De Santis F, Rossi A et al., Liposomes Loaded With Phosphatidylinositol 5-Phosphate Improve the Antimicrobial Response to Pseudomonas aeruginosa in Impaired Macrophages From Cystic Fibrosis Patients and Limit Airway Inflammatory Response, Frontiers in immunology vol. 11 532225. 2 Oct. 2020

OTHER RESULTS

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models

FFC#4/2023

Pseudopaline–aztreonam conjugates exhibited enhanced antimicrobial activity against Pseudomonas aeruginosa compared to aztreonam alone

FFC#10/2023

Several drugs already approved for human use inhibit the growth of P. aeruginosa, its virulence, or its ability to form biofilms in vitro