Mycobacteria

Question

Hello,
My 6 year old son just had a sputum culture that shows the presence of mycobacteria.
I wished to have more information on this germ and whether my son will have this germ all the life as I gather that it is resistant to antibiotics.
Also I'd like to know where is the research regarding its mutations G542X and 1811 + 1.6kba> G
Thank you in advance for your response.

Answer

Hello,
You have actually posted two questions in one.
Concerning the mycobacteria, they are bacilli whose wall is rich in wax (or mycolic acids, hence their name) which allows them to retain dyes despite the combined action of dilute acid and alcohol (hence their other name: acid-fast bacilli - AFB). This feature is used for microscopic identification after a special staining, Ziel-Neelsen staining. The culture requires time (the germ grows slowly) and a seeding on a special medium (Lowenstein medium).
We have to distinguish, on one hand, mycobacteria responsible for tuberculosis with often species-specific, human, avian or bovine (Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium bovis ...), on the other hand, non-tuberculous mycobacteria. These NTM are widespread in the environment but rarely pathogenic (resulting in disease) except in case of either an immunocompromised disease or a pulmonary inflammatory disease. These germs are thus more often found in people with CF (PWCF). Usually the species involved belong to the Mycobacterium avium or to Mycobacterium abscessus complex. Their discovery in sputum culture (sputum smear) does not necessarily mean that the germ is responsible for respiratory disease. It may be an environmental germ which has contaminated seeding or a germ actually present in the sputum but not pathogenic.
Given the increasing frequency of this germ CF patients, it is recommended to perform a systematic sampling for specific research of NTM once or twice a year.
International guidelines for management of NTM in CF patients are going to be published. Treatment is indicated when there are elements evoking the germ responsibility in the clinical and radiological worsening respiratory symptoms despite antibiotic therapy directed against other germs found in the sputum culture (or sometimes in product of broncho-alveolar lavage) and in microscopic examination. Because ATB resistance to the NTM is common, it is important to get the resistance profile of the germ in order to lead the choice of antibiotics if treatment is indicated.
Regarding your child, having once found the germ does not mean that it will sprout all over the life : in accordance with the guidelines, if respiratory symptoms persist despite antibiotic treatment against other germs found in sputum, it is first necessary to check its persistence by other sampling and its responsibility of the symptoms.

Regarding the mutations of the cystic fibrosis gene carried by your child:
The G542X mutation is the second most common mutation in the CFTR gene after the main F508del mutation. This is a Class 1 mutation, that means the synthesis of the protein encoded by the gene is interrupted prematurely due to a "stop" codon (hence the name stop mutation) and is destroyed in the nucleus prior to migration into the cell.
The mutation 1811 + 1.6kba> G is a much more rare mutation, indeed exceptional. It is only found in 34 of the more than 40,000 patients registered in the CFTR2 international database. Its classification is controversial because of the scarcity of studies on this mutation. In a publication in the journal "Thorax" in 2005, it is considered a Class 5 mutation resulting in a decrease in the amount of protein (the chloride channel) at the cell membrane. In fact, other teams consider it a Class 1 mutation because the structure of the protein changes must logically lead to a malfunction due to a “frameshift”.
Therapeutic trials specifically for patients with one or two class 1 mutations are ongoing. The results are not announced before several months.
Hope to have answered your questions.
Sincerely.
Gilles RAULT, Roscoff CF Center
and Marie-Pierre AUDREZET, Molecular Genetics Laboratory, Brest UH

03.12.2014