Biofilm aggregates and the host airway-microbial interface

Abstract

Biofilms are multicellular microbial aggregates that can be associated with host mucosal epithelia in the airway, gut, and genitourinary tract. The host environment plays a critical role in the establishment of these microbial communities in both health and disease. These host mucosal microenvironments however are distinct histologically, functionally, and regarding nutrient availability. This review discusses the specific mucosal epithelial microenvironments lining the airway, focusing on: i) biofilms in the human respiratory tract and the unique airway microenvironments that make it exquisitely suited to defend against infection, and ii) how airway pathophysiology and dysfunctional barrier/clearance mechanisms due to genetic mutations, damage, and inflammation contribute to biofilm infections. The host cellular responses to infection that contribute to resolution or exacerbation, and insights about evaluating and therapeutically targeting airway-associated biofilm infections are briefly discussed. Since so many studies have focused on Pseudomonas aeruginosa in the context of cystic fibrosis (CF) or on Haemophilus influenzae in the context of upper and lower respiratory diseases, these bacteria are used as examples. However, there are notable differences in diseased airway microenvironments and the unique pathophysiology specific to the bacterial pathogens themselves.

In vitro modelling of bacterial pneumonia: a comparative analysis of widely applied complex cell culture models

“…Although these models allow the study of biofilm–cell interactions, they lack the ability to study the initiation process of biofilm formation in a cellular environment. As many questions on the influence of specific airway host cells, genetic predisposition, and the lung microenvironment on the formation and function of biofilms remain unanswered, complex biofilm models could help in our understanding and managing of biofilm-related infections (Hall-Stoodley and McCoy 2022 ).…”

Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease

“…98 Nevertheless, despite much in-vitro and experimental model work on biofilms, evidence for their presence in patients with CSLD is relatively limited. They have however, been detected in the sputum of adults with CF and COPD, 99,100 and in bronchoalveolar lavage (BAL) fluid from children with PBB and bronchiectasis. 101 Importantly, by using fluorescent in-situ hybridization (FISH) staining in a small subset of BAL samples, researchers were able to demonstrate the polymicrobial nature of the biofilms, which included in addition to NTHi other recognized respiratory pathogens (Streptococcus pneumoniae, M. catarrhalis) and upper airway commensals, such as Prevotella species.…”

Autoaggregation inStreptococcus intermediusis driven by the Pel polysaccharide

“…There is increasing evidence that suggests aggregates formed in media or host fluids exhibit the same characteristics as surface attached biofilms and are increasingly being recognized for their role in pathogenicity (6, 9–12). Multiple chronic infections have been linked to aggregates including chronic infections in cystic fibrosis (7, 13), dermal wounds (9, 11) and otitis media (14). Bacteria in both surface attached biofilms and aggregates are recalcitrant to antibiotic treatment and are protected from the immune system.…”