Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus

Ulluwishewa, Dulantha; Wang, Liang; Pereira, Callen; Flynn, Stephanie; Cain, E.; Stick, Stephen M.; Reen, F. Jerry; Ramsay, Joshua P.; O’Gara, Fergal

doi:10.1099/mic.0.000317

Cited by 10 publications

(10 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thickened cell walls is a common feature of DAP- and VAN-resistant staphylococci [ 27 , 28 ] resulting from changes to one or more of several global regulators ( graRS , vraSR , walKR ) or cell wall biosynthetic machinery [ 29 ]. In contrast to other potential contributors to cell wall thickening, TagGH activity was specifically associated with the ability of staphylococci to induce biofilm production in the presence of bile components [ 30 ]. Therefore, we examined the response of study isolates to biofilm induction with either bovine bile or deoxycholate.…”

Section: Resultsmentioning

confidence: 99%

“…Biofilm polystyrene attachment assay was performed in Trypticase Soy Broth with 0.1% dextrose in tissue culture treated 24 well plates (Costar, Corning, NY, USA) and measured using crystal violet as described previously [ 52 ]. Biofilm production media was fortified with bovine bile (0.03%, Sigma-Aldrich) or sodium deoxycholate (100μM, Sigma-Aldrich) as indicated [ 30 ]. Bacterial survival in heparinated human blood (Zenbio) was determined by dilution plating following 1h and 3h exposure as described previously [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Miller

Monk²,

Szubin³

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Miller

Monk²,

Szubin³

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Thus, environmental selection would allow the stable settlement of bile-tolerant microorganisms. Interestingly, we have reported that several classical CF pathogens tolerate BAs, adopting chronic lifestyles in the presence of these molecules [12,13,73]. This adaptive process could lead to an increase in their ecological resilience behaviour, and ultimately facilitate the establishment of persistent chronic infections in the CF lungs.…”

Section: Discussionmentioning

confidence: 97%

Bile Acid Signal Molecules Associate Temporally with Respiratory Inflammation and Microbiome Signatures in Clinically Stable Cystic Fibrosis Patients

et al. 2020

Self Cite

View full text Add to dashboard Cite

Cystic fibrosis (CF) is a congenital disorder resulting in a multisystemic impairment in ion homeostasis. The subsequent alteration of electrochemical gradients severely compromises the function of the airway epithelia. These functional changes are accompanied by recurrent cycles of inflammation–infection that progressively lead to pulmonary insufficiency. Recent developments have pointed to the existence of a gut–lung axis connection, which may modulate the progression of lung disease. Molecular signals governing the interplay between these two organs are therefore candidate molecules requiring further clinical evaluation as potential biomarkers. We demonstrate a temporal association between bile acid (BA) metabolites and inflammatory markers in bronchoalveolar lavage fluid (BALF) from clinically stable children with CF. By modelling the BALF-associated microbial communities, we demonstrate that profiles enriched in operational taxonomic units assigned to supraglottic taxa and opportunistic pathogens are closely associated with inflammatory biomarkers. Applying regression analyses, we also confirmed a linear link between BA concentration and pathogen abundance in BALF. Analysis of the time series data suggests that the continuous detection of BAs in BALF is linked to differential ecological succession trajectories of the lung microbiota. Our data provide further evidence supporting a role for BAs in the early pathogenesis and progression of CF lung disease.

show abstract

“…Bile acids are biological detergents that facilitate the digestion and absorption of lipids and fat-soluble vitamins [43]. Apart from these functions, they are also involved in many biological signalling and regulatory events, including metabolic tuning, modulation of the host immune responses, control of microbial communities, and regulation of pathogenicity mechanisms in respiratory pathogens [16,18,19,[43][44][45][46][47]. Previous research has shown that the presence of BAs in BALF and sputum from CF patients and lung transplant recipients is associated with inflammatory markers, suggesting a role for BAs in the progression of CF respiratory disease and lung transplant rejection [34,35,48].…”

Section: Discussionmentioning

confidence: 99%

“…Among potential host triggers that may be implicated in modulating host-microbiota interactions and inflammation in the CF lung through the gut-lung axis, bile acids (BAs) have been demonstrated to influence both biofilm formation and antibiotic tolerance in a number of respiratory pathogens [16][17][18]. Bile acids have also been demonstrated to regulate the immune response of airway epithelial cells by repressing HIF1 signalling through destabilisation of HIF1-α and inducing the production of the pro-inflammatory cytokine interleukin 6 (IL6) [16,19].…”

Section: Introductionmentioning

confidence: 99%

The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.

show abstract

Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus

Cited by 10 publications

References 58 publications

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia

Bile Acid Signal Molecules Associate Temporally with Respiratory Inflammation and Microbiome Signatures in Clinically Stable Cystic Fibrosis Patients

The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns

Contact Info

Product

Resources

About