Influence of the lung microbiome on antibiotic susceptibility of cystic fibrosis pathogens

Abstract

The lungs of patients with cystic fibrosis (CF) are colonised by a microbial community comprised of pathogenic species, such as Pseudomonas aeruginosa and Staphylococcus aureus, and microorganisms that are typically not associated with worse clinical outcomes (considered as commensals). Antibiotics directed at CF pathogens are often not effective and a discrepancy is observed between activity of these agents in vitro and in the patient. This review describes how interspecies interactions within the lung microbiome might influence the outcome of antibiotic treatment targeted at common CF pathogens. Protective mechanisms by members of the microbiome such as antibiotic degradation (indirect pathogenicity), alterations of the cell wall, production of matrix components decreasing antibiotic penetration, and changes in metabolism are discussed. Interspecies interactions that increase bacterial susceptibility are also addressed. Furthermore, we discuss how experimental conditions, such as culture media, oxygen levels, incorporation of host–pathogen interactions, and microbial community composition may influence the outcome of microbial interaction studies related to antibiotic activity. Hereby, the importance to create in vitro conditions reflective of the CF lung microenvironment is highlighted. Understanding the role of the CF lung microbiome in antibiotic efficacy may help find novel therapeutic and diagnostic approaches to better tackle chronic lung infections in this patient population.

“It Takes a Village”: Mechanisms Underlying Antimicrobial Recalcitrance of Polymicrobial Biofilms

“…Antibiotic recalcitrance mechanisms within polymicrobial biofilms include horizontal gene transfer of antibiotic resistance genes, enzymatic degradation of antibiotics (by ␤-lactamases), the induction of transcriptional changes by primary metabolites (e.g., indole and 2,3-butanedione) or quorum sensing signals (e.g., DSF and farnesol), inhibition of electron transport (by HQNO), and changes in membrane fluidity (by HQNO). Chronic polymicrobial infections, such as those associated with airway infections in patients with CF, are likely impacted by many of these mechanisms, as has been highlighted in a recent literature review (181).…”

Lung Microbiome Participation in Local Immune Response Regulation in Respiratory Diseases

“…In adults with CF, the microbiome has been observed to be more stable, despite the use of antibiotics to Streptococcus, Prevotella, Rothia, and Veillonella found in this group of patients; in addition, the decrease in bacterial richness is associated with worse respiratory function [46]. The changes in the composition of the lung microbiome in patients with CF and the alterations that originate in the pulmonary ecosystem may be the cause of the low effectiveness of antibiotics in these patients [47]. Through metagenomic studies, it is possible to identify the dominant pathogens, as well as their resistance to antibiotics, quickly and accurately compared to bacterial cultures [48], contributing to improving the quality of life of patients with CF.…”

The Lung Microbiome of Three Young Brazilian Patients With Cystic Fibrosis Colonized by Fungi

“…On the other hand, susceptible bacteria can acquire temporary resistance to antibiotics due to microbial interactions in the lung environment. Resistant bacteria can modify antibiotics, diminishing their efficacy, or biofilm formation may limit and dilute the minimum inhibitory concentration values resulting in sublethal doses or fungi that may protect bacteria from forming hyphal barriers (Vandeplassche et al, 2019).…”