Mycobacterium abscessus (Mab) can infect the lungs of people with cystic fibrosis, causing a serious pathology, difficult to eradicate due to its resistance to drugs. In particular, dormant and persistent Mab are highly drug-resistant, hindering therapeutic success.
The researchers used in vitro cultures of M. abscessus under conditions of aeration, which stimulates bacterial growth, or oxygen depletion, in which the bacteria enter a dormant form. They also studied forms that survive drugs, the so-called persisters.
The different forms of Mab were used to study its drug response and physiology. Regarding drugs, 3 beta-lactams, 2 tetracyclines and an oxazolidinone were used. These drugs were tested in both the replicative and dormant forms. Furthermore, their activity was tested in combination with bedaquiline+amikacin (B+A), effective on Mab. The physiology of the various forms of Mab has instead been studied from the point of view of gene expression. Finally, tests were carried out to verify which drugs are active on drug-surviving cells, the persistent forms.
Beta-lactam drugs are effective and increase the effectiveness of B+A in replicating bacteria. The gene expression studies showed that dormant and persistent bacteria are very similar, hence the common greater resistance to drugs. Finally, the addition of drugs at a later time than B+A increased its effectiveness compared to the simultaneous addition.
This study has opened to a new approach towards the search for an improved therapy, in which the most resistant forms must be taken into account. The models presented could be used to find combinations that are effective on all bacterial forms.