Interplay of Mycobacterium abscessus and Pseudomonas aeruginosa in coinfection: Biofilm Dynamics and Host Immune Response

Abstract

The incidence of infection by nontuberculous mycobacteria, mainly Mycobacterium abscessus, in patients with cystic fibrosis and other chronic pulmonary illnesses is increasing, translating into an acceleration in the decline of lung function. In most cases, M. abscessus coinfects with Pseudomonas aeruginosa, the most common pathogen in these chronic diseases. However, it is unknown how these two bacterial species interact when coinfecting. This study aims to explore the behavior of both species in three relevant pathogenic settings: dual-species biofilm development using a recently developed method to monitor individual species in dual-species biofilms; coinfection in bronchial epithelial cells using in vitro assays; and in vivo coinfection using the Galleria mellonella model. The results demonstrate the capability of both species to form stable mixed biofilms and to reciprocally inhibit single-biofilm progression. Coinfections in bronchial epithelial cells were correlated with significantly decreased cell viability, while in G. mellonella, coinfections induced lower survival rates than individual infections. Outstandingly, the analysis of the immune response triggered by each bacterium in bronchial epithelial cell assays and G. mellonella larvae revealed that P. aeruginosa induces the overexpression of proinflammatory and melanization cascade responses, respectively. In contrast, M. abscessus and P. aeruginosa coinfection significantly inhibited the immune response in both models, resulting in worse consequences for the host than those generated by single P. aeruginosa infection. Overall, the presence of M. abscessus produces a decline in the immune responses that worsens the infection and compromises the host. ImportanceThe appearance of bacterial infections in the respiratory tract of patients with chronic respiratory diseases suppose a serious and difficult to treat health problem. This complication is exacerbated by the increase resistance against antibiotics generated by pathogenic microorganisms. The most common and virulent pathogenic bacteria reported in the respiratory airway is Pseudomonas aeruginosa. It is a Gram-negative, ubiquitous, and intrinsic resistant to antibiotics bacteria. However, the incidence of a rapidly growing, multi-drug resistant mycobacteria; Mycobacterium abscessus, is growing worldwide. The pulmonary coinfection by both pathogens is directly related with higher rates of morbidity and mortality of patients. The significance of our research is characterizing the behavior of these two pathogens when they coinfects together, exploring the immune response triggered by the host and its impact in the survival. The purpose is enhancing the limited understanding we have of this clinically relevant coinfection to favor the development of new effective treatments.