Acute polymicrobial airway infections: analysis in cystic fibrosis mice

Abstract

Cystic fibrosis (CF) is a genetic disorder affecting epithelial ion transport, which among other impacts results in defective mucociliary clearance and innate defenses in the respiratory tract. Consequently, people with CF experience lifelong infections of the respiratory mucosa that are chronic and polymicrobial in nature. Young children with CF are initially colonized by opportunists like nontypeable Haemophilus influenzae (NTHi), which normally resides within the microbiome of the nasopharynx and upper airways and can also cause infections of the respiratory mucosa that include bronchitis and otitis media. NTHi is typically supplanted by other microbes as patients age; for example, people with CF are often chronically infected with mucoid strains of Pseudomonas aeruginosa , which prior work in our laboratory has shown to promote colonization and persistence by other opportunists that include Stenotrophomonas maltophilia . Our previous work has shown that polymicrobial infection impacts host colonization and persistence of incoming microbes via diverse mechanisms that include priming of host immunity that can promote microbial clearance, and cooperativity within polymicrobial biofilms, which can promote persistence. In infection studies with BALB/c Cftrtm1UNC mice, results showed, as previously observed for WT BALB/c mice, preceding infection with NTHi decreased colonization and persistence by P. aeruginosa . Likewise, polymicrobial infection of BALB/c Cftrtm1UNC and C57BL/6 Cftrtm1UncTg(FABPhCFTR)1Jaw/J mice showed correlation between S. maltophilia and P. aeruginosa , with increased bacterial colonization and lung pathology. Based on these results, we conclude that our previous observations regarding polymicrobial infections with CF opportunists in WT mice are also validated using CF mice.

Lung microbiome: new insights into the pathogenesis of respiratory diseases

“… 232 P. aeruginosa can cause chronic infection, which is associated with an increased risk of pulmonary exacerbation (PE) and increased colonization of diverse pathogens, failure to recover lung function after PE, and rapid loss of lung function over time, causing premature death in patients with CF. 233 , 234 Some of these characteristics may be related to gene mutations. Some genes, such as quorum sensing regulators involved in the expression of the virulence factor lasR, are common mutation targets.…”

Comparative genomics of clinical Stenotrophomonas maltophilia isolates reveals genetic diversity which correlates with colonization and persistence in vivo

“…While some human-infection-associated factors have been identified, isolates must primarily rely on factors that also promote their survival in environmental situations to colonize the human lung [2,[17][18][19][20][21]. Our previous work described a cooperative interaction between S. maltophilia and P. aeruginosa where damage to the lung epithelium by P. aeruginosa contributed to the increased persistence of S. maltophilia [22][23][24]. These studies were, however, restricted to only a few strains, and given the amount of genetic diversity present in S. maltophilia, it is likely that genetic content plays a role in determining both the ability of an isolate to successfully infect a human host, and the amount of cooperativity that is seen with P. aeruginosa.…”

“…aeruginosa contributed to the increased persistence of S. maltophilia [22–24]. These studies were, however, restricted to only a few strains, and given the amount of genetic diversity present in S.…”