Antibiotic resistance alters the ability of Pseudomonas aeruginosa to invade the respiratory microbiome

The emergence and spread of antibiotic resistance in bacterial pathogens is a global health threat. One important unanswered question is how antibiotic resistance influences the ability of a pathogen to invade the host-associated microbiome. Here we investigate how antibiotic resistance impacts the ability of the opportunistic bacterial pathogen Pseudomonas aeruginosa to invade the respiratory microbiome, by measuring the ability of P. aeruginosa spontaneous antibiotic resistant mutants to invade pre-established cultures of commensal respiratory microbes. We find that commensal respiratory microbes tend to inhibit the growth of P. aeruginosa, and antibiotic resistance is a double-edged sword that can either help or hinder the ability of P. aeruginosa to overcome this inhibition. The directionality of this help or hinderance depends on both P. aeruginosa genotype and respiratory microbe identity. Antibiotic resistance facilitates the invasion of P. aeruginosa into Staphylococcus lugdunensis, yet impairs invasion into Rothia mucilaginosa and Staphylococcus epidermidis. Streptococcus species provide the strongest inhibition to P. aeruginosa invasion, and this is maintained regardless of antibiotic resistance genotype. Our study demonstrates how antibiotic resistance can alter the ability of a bacterial pathogen to invade the respiratory microbiome and suggests that attempts to manipulate the microbiome should focus on promoting the growth of commensals that can provide robust inhibition of both wildtype and antibiotic resistant pathogen strains.