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| Pàgina inicial > Articles > Articles publicats > Genetic Adaptation and Acquisition of Macrolide Resistance in spp. during Persistent Respiratory Tract Colonization in Chronic Obstructive Pulmonary Disease (COPD) Patients Receiving Long-Term Azithromycin Treatment |
(Hospital Universitari de Bellvitge) (Hospital Universitari de Bellvitge) (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT)) (Hospital Universitari de Bellvitge) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Hospital Universitari de Bellvitge)| Data: | 2022 |
| Resum: | Patients with chronic obstructive pulmonary disease (COPD) benefit from the immunomodulatory effect of azithromycin, but long-term administration may alter colonizing bacteria. Our goal was to identify changes in and during azithromycin treatment. Fifteen patients were followed while receiving prolonged azithromycin treatment (Hospital Universitari de Bellvitge, Spain). Four patients (P02, P08, P11, and P13) were persistently colonized by for at least 3 months and two (P04 and P11) by H. parainfluenzae. Isolates from these patients (53 and 18 H. parainfluenzae) were included to identify, by whole-genome sequencing, antimicrobial resistance changes and genetic variation accumulated during persistent colonization. All persistent lineages isolated before treatment were azithromycin-susceptible but developed resistance within the first months, apart from those belonging to P02, who discontinued the treatment. isolates from P08-ST107 acquired mutations in 23S rRNA, and those from P11-ST2480 and P13-ST165 had changes in L4 and L22. In H. parainfluenzae, P04 persistent isolates acquired changes in rlmC, and P11 carried genes encoding MefE/MsrD efflux pumps in an integrative conjugative element, which was also identified in P11-ST147. Other genetic variation occurred in genes associated with cell wall and inorganic ion metabolism. Persistent strains all showed changes in licA and hgpB genes. Other genes (lex1, lic3A, hgpC, and fadL) had variation in multiple lineages. Furthermore, persistent strains showed loss, acquisition, or genetic changes in prophage-associated regions. Long-term azithromycin therapy results in macrolide resistance, as well as genetic changes that likely favor bacterial adaptation during persistent respiratory colonization. IMPORTANCE The immunomodulatory properties of azithromycin reduce the frequency of exacerbations and improve the quality of life of COPD patients. However, long-term administration may alter the respiratory microbiota, such as , an opportunistic respiratory colonizing bacteria that play an important role in exacerbations. This study contributes to a better understanding of COPD progression by characterizing the clinical evolution of in a cohort of patients with prolonged azithromycin treatment. The emergence of macrolide resistance during the first months, combined with the role of as a reservoir and source of resistance dissemination, is a cause for concern that may lead to therapeutic failure. Furthermore, genetic variations in cell wall and inorganic ion metabolism coding genes likely favor bacterial adaptation to host selective pressures. Therefore, the bacterial pathoadaptive evolution in these severe COPD patients raise our awareness of the possible spread of macrolide resistance and selection of host-adapted clones. |
| Ajuts: | Agencia Estatal de Investigación RTI2018-096369-B-I00 Ministerio de Economía y Competitividad PI16/00977 Ministerio de Sanidad y Consumo CB06/06/0037 Ministerio de Sanidad y Consumo CB06/06/1102 Instituto de Salud Carlos III CP19/00096 Ministerio de Educación, Cultura y Deporte FPU16/02202 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Haemophilus influenzae ; Haemophilus parainfluenzae ; Persistence ; Macrolide resistance ; Azithromycin ; Adaptation |
| Publicat a: | Microbiology Spectrum, Vol. 11 (december 2022) , ISSN 2165-0497 |
