FFC#18/2021

New weapons against Mycobacterium abscessus and other nontuberculous Mycobacteria

FFC#18/2021

New weapons against Mycobacterium abscessus and other nontuberculous Mycobacteria

PRINCIPAL INVESTIGATOR

Maria Rosalia Pasca (Università degli Studi di Pavia, Dip. di Biologia e Biotecnologia Lazzaro Spallanzani)

Partner

Vadim Makarov (Federal Research Center, Moscow), Santiago Ramón García (University of Zaragoza), Enrico Tortoli (Div. di Immunologia, Trapianti e Malattie Infettive – HSR, Milano)

RESEARCHERS

15

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

1 year

GOAL

€ 70.000 €

RESULTS

The incidence of Mycobacterium abscessus (Mab) is increasing among cystic fibrosis (CF) individuals worldwide. Mab drug therapy is long up to 2 years and treatment failure is linked to an accelerated lung function decline. The current drug pipeline is alarmingly sparse, thus new antibiotics with a novel mechanism of action active against this emerging pathogen are needed. To pursue this aim, we used microbiological, chemical and biochemical procedures.
We screened more than 700 compounds ad hoc synthesized and identified only one, with bactericidal activity against Mab. This molecule is also active against multidrug resistant Mab clinical isolates, Mab biofilm and suitable for combinatorial therapy since no antagonism was identified among a panel of drugs clinically used for Mab treatment. Furthermore, this compound is active in mice infected with Mab by intranasal administration. This compound is also active against other microorganisms that can cause pulmonary diseases among CF individuals such as Acinetobacter baumannii and Staphylococcus aureus. We showed that this compound inhibits cell bacterial division, in particular FtsZ enzyme.

All the results indicate that this compound is a new promising drug candidate against Mab.
We have just filed a patent regarding the activity of this compound with the co-ownership of FFC Ricerca and another one is in preparation.


Abstract presentati a congressi scientifici

  • A drug candidate against Mycobacterium abscessus and other cystic fibrosis pathogens. EMBO Workshop on Tuberculosis 2022. From innovation to intervention, Paris, France, September 12- 16, 2022
  • A new weapon against Mycobacterium abscessus. 45th European Cystic Fibrosis Conference, Rotterdam, the Netherlands, June 8-11 2022. J Cyst Fibros 21S1 (2022) S2, WS01.04
  • Study of in vitro and in vivo activity of a novel compound against Mycobacterium abscessus for the treatment of cystic fibrosis infections. 32nd ECCMID, the European Congress of Clinical Microbiology and Infectious Diseases, Lisbon, Portugal, April 23–26 2022. Abstract: 1374 / P0163.

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