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Review
. 2021 Jul 7;10(7):827.
doi: 10.3390/antibiotics10070827.

Polymicrobial Interactions in the Cystic Fibrosis Airway Microbiome Impact the Antimicrobial Susceptibility of Pseudomonas aeruginosa

Emma Reece  1 , Pedro H de Almeida Bettio  1 , Julie Renwick  1
Affiliations
Review

Polymicrobial Interactions in the Cystic Fibrosis Airway Microbiome Impact the Antimicrobial Susceptibility of Pseudomonas aeruginosa

Emma Reece et al. Antibiotics (Basel). .

Abstract

Pseudomonas aeruginosa is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial interactions have been shown to play an important role in shaping P. aeruginosa pathogenicity and resistance. P. aeruginosa can cause chronic infections that once established are almost impossible to eradicate with antibiotics. CF patients that develop chronic P. aeruginosa infection have poorer lung function, higher morbidity, and a reduced life expectancy. P. aeruginosa adapts to the CF airway and quickly develops resistance to several antibiotics. A perplexing phenomenon is the disparity between in vitro antimicrobial sensitivity testing and clinical response. Considering the CF airway is host to a diverse community of microorganisms or 'microbiome' and that these microorganisms are known to interact, the antimicrobial resistance and progression of P. aeruginosa infection is likely influenced by these microbial relationships. This review combines the literature to date on interactions between P. aeruginosa and other airway microorganisms and the influence of these interactions on P. aeruginosa tolerance to antimicrobials.

Keywords: Pseudomonas aeruginosa; antibiotic resistance; cystic fibrosis; microbiome; polymicrobial interactions.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
P. aeruginosa and S. aureus interactions leading to changes in antibiotic resistance. (1) AQs produced by Pa impact Sa planktonic growth, decreasing ATP generation and active transport and so uptake of AMG. (2) Sa Nor efflux pumps are upregulated in the presence of Pa, causing increased resistance to TET and CPFX. (3) Pa produced AQs, HQNO, and HAQ increase Sa biofilm production and membrane fluidity and decrease resistance to membrane-targeted antibiotics. Studies differ in increase/decreased resistance to TOBI and increase/decrease Sa biofilm. (4) Sa-produced SpA interacts with Pa exopolysaccharide Psl, changing Pa biofilm architecture and resistance to antibiotics. (5) Prolonged mixed biofilms and long-term exposure to HQNO induce Sa SCVs. Pa in mixed biofilms increases siderophore production and produces truncated LPS both linked to AMR to antibiotics targeting cell wall biosynthesis and protein synthesis but unchanged or decreased resistance to other antibiotics. (6) Environmental conditions such as anoxia and adaptation to host increase antibiotic resistance and commensal cooperative behaviour. Pa = P. aeruginosa, Sa = S. aureus, Abx = antibiotics, AMG = aminoglycosides, SCV = small colony variant, TET = tetracycline, CPFX = ciprofloxacin, FQ = fluoroquinolones, PCMX = chloroxylenol, βL = beta-lactam, TOBI = tobramycin, SpA = Staphylococcal protein A, Psl = biofilm exopolysaccharide, pyl = pyochelin, pyv = pyoverdine, AQ = 2-alkyl-4-(1H)-quinolones, HQNO = 4-hydroxy-2-heptylquinoline-N-oxide, HAQ = 4-hydroxy-2-alkylquinoline.
Figure 2
Figure 2
Passive and active mechanisms of antibiotic tolerance/resistance developed by P. aeruginosa during polymicrobial interactions. (A) Neutralisation of antibiotics by cleaving enzymes produced by other community members; (B) ‘hiding’ in multispecies biofilms reducing access of antibiotics; (C) changes in cell wall architecture, including truncated LPS, increased expression of efflux pumps, or reduced activity of membrane transporters; (D) changes in metabolism resulting in alterations to growth and quorum sensing, development of SCVs, and conversion to fermentative growth; (E) increased or decreased production of ECM and biofilm growth; and (F) transfer of mobile ARGs via bacteriophage. Abx = antibiotics, ECM = extracellular matrix, SCV = small colony variant, QS = quorum sensing, tLPS = truncated lipopolysaccharide, ARGs = antibiotic resistant genes.
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