Lindsay G Pauls, Matheus Mertz Ribeiro, Gustavo H Goldman, Stephen K Dolan
The respiratory tract harbors complex, dynamic microbial communities during infection, including bacteria (e.g., Pseudomonas aeruginosa and Staphylococcus aureus), fungi (e.g., Aspergillus fumigatus and Cryptococcus neoformans), and the resident respiratory microbiota. Within this ecosystem, microbes engage in cooperative and competitive interactions shaped by nutrient availability, immune modulation, and interkingdom chemical signaling, collectively influencing microbial persistence and pathogenic potential. While traditional studies have largely focused on single-pathogen infections, emerging evidence highlights the role of polymicrobial interactions-both synergistic and antagonistic-between pathogens and the respiratory microbiota in shaping disease progression in respiratory disorders. This minireview summarizes recent advances in understanding these complex microbial interactions and highlights key knowledge gaps and future directions in this rapidly evolving field.