Chronic lung infections in people with cystic fibrosis (CF) are characterized by recurrent pulmonary exacerbations. The presence of so-called viable but non-culturable bacteria (VBNCs) has been detected using analysis techniques independent of bacterial culture: VBNCs are antibiotic-insensitive bacteria that cannot be detected by routine culture methods (due to their inability to grow on bacterial media), although they remain viable and potentially virulent. Better detection of both culturable and non-culturable persistent forms is therefore a prerequisite for the development of effective eradication strategies.
Sputum samples from 102 people with CF were used, with a total of 407 samples analyzed. Sputum samples (4 from each person with CF enrolled in the study) were analyzed by both culture assays and molecular biology techniques, such as qPCR, species-specific for the presence of VBNC forms.
Samples were assayed for the presence of the following bacteria: P. aeruginosa (PA), A. xylosoxidans (AX), S. maltophilia (SM), methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA).
Microbiologically, it was observed that in people who started CFTR modulator therapy, the presence of certain bacterial species was not detected in the lower respiratory tract, but in several cases VBNC cells were detected in the same sputum samples, supporting the hypothesis that microorganisms that chronically colonise the lower respiratory tract of people with CF persist even when culture results are negative, resulting dormant and non-culturable.
Treatment with CFTR modulators seemed to ameliorate FEV1 values in the treated pwCF, either presenting or not VBNC cells, although not in a significant manner.
Furthermore, it was observed that VBNC bacterial forms can develop in people with CF with chronic lung infection, survive antibiotic therapy, regain cultivability and proliferate, hindering eradication of the infection.
Finally, PA and MSSA were found to be the bacteria most prone to develop VBNC variants.
The results of this study highlight the urgency of supplementing culture techniques with more sensitive and specific molecular techniques for both viable and non-viable bacterial forms; they also highlight the lack of bacterial eradication in people with CF with chronic or intermittent infection.
Further studies on the effect of CFTR modulators in eradicating the infection itself will be needed.