Catheter-associated Mycobacterium intracellulare biofilm infection in C3HeB/FeJ mice

Abstract

AbstractNon-tuberculosis mycobacterial (NTM) diseases are steadily increasing in prevalence and mortality worldwide. Mycobacterium avium and M. intracellulare, the two major pathogens of NTM diseases, are resistant to antibiotics, and chlorine, necessitating their capacity to survive in natural environments (e.g. soil and rivers) and disinfected municipal water. They can also form biofilms on artificial surfaces to provide a protective barrier and habitat for bacilli, which can cause refractory systemic disseminated NTM disease. Therefore, preventing biofilm formation by these pathogens is crucial; however, not many in vivo experimental systems and studies on NTM biofilm infection are available. This study develops a mouse model of catheter-associated systemic disseminated disease caused by M. intracellulare that reproduces the pathophysiology of catheter-associated infections observed in patients undergoing peritoneal dialysis. In addition, the bioluminescence system enabled noninvasive visualization of the amount and distribution of bacilli in vivo and conveniently examine the efficacy of antimicrobials. Furthermore, the cellulose-based biofilms, which were extensively formed in the tissue surrounding the catheter insertion site, reduced drug therapy effectiveness. Overall, this study provides insights into the cause of the drug resistance of NTM and may guide the development of new therapies for NTM diseases.