FFC#12/2020

New drug combinations against non-tuberculous mycobacteria infections in cystic fibrosis

FFC#12/2020

New drug combinations against non-tuberculous mycobacteria infections in cystic fibrosis

PRINCIPAL INVESTIGATOR

Lanfranco Fattorini (Istituto Superiore di Sanità, Roma, Dip. di Malattie Infettive)

Partner

Emanuele Borroni (Ospedale San Raffaele, Milano, Unità patogeni batterici emergenti)

RESEARCHERS

10

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 52.000 €

RESULTS

The Mycobacterium abscessus MAB-10 strain was set-up in a 40 days in-vitro culture and different drugs combinations were tested. Combinations of bedaquiline (a new anti-tuberculosis drug), amikacin, rifabutin, moxifloxacin, clofazimine (an anti-leprosy drug) and metronidazole (an anti-anaerobic drug) were the most promising, futhermore, bedaquiline and amikacin combinations were the most active against MABs in both anaerobic and dormient phases (dormant persisters). From the results of the tests, the researchers observed that dormant persisters cells living in the biofilm are more difficult to kill than those found in the aerobic phase. The research team believes that prolonged treatment for periods greater than 49 days with these combinations can kill cells from clinical strains in both the aerobic and dormant phases. The most promising combinations will be identified by the results of the experiments that measure the minimum concentration at which the drug is active. The data on the efficacy of drugs in relation to the duration of incubation may explain why MAB-infected CF patients need months of antibiotic therapy. The research group’s work continues with the FFC#17/2021 project in which Dr. Fattorini, given his retirement, passes the coordination to Dr. Federico Giannoni.

OTHER RESULTS

FFC#2/2022

Characterization of CFTR modulators mechanism of action via Photo-Affinity Labeling (PAL) approach

FFC#6/2022

Search for drug combinations killing Mycobacterium abscessus in cystic fibrosis

FFC#1/2021

Multiomics exploration of the CF primary bronchial epithelium lipidome and its role on CFTR rescue