Interspecies interactions alter the antibiotic sensitivity of Pseudomonas aeruginosa

Microbiology Spectrum, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

ABSTRACT Polymicrobial infections are that caused by multiple pathogens and common in patients with cystic fibrosis (CF). Although polymicrobial associated poor treatment responses CF, the effects of ecological interactions between co-infecting on antibiotic sensitivity outcome poorly characterized. To this end, we systematically quantified impact these Pseudomonas aeruginosa for nine antibiotics medium conditioned 13 secondary fibrosis-associated bacterial fungal through time-kill assays. We fitted pharmacodynamic models to kill curves each antibiotic-species combination found interspecies changing P. abundant. Interactions lower more than those increase it, generally substantial reductions increases sensitivity. For a selection species, performed pharmacokinetic–pharmacodynamic modeling treatment. predicted can either improve or reduce response extent is rendered ineffective from previously effective dosing schedule vice versa . In summary, show quantifying interaction as parameters necessary determine abundance which affect infections. IMPORTANCE (CF) patients, chronic respiratory tract often polymicrobial, involving simultaneously. difficult treat they respond unexpectedly treatment, might possibly be explained because influence other’s sensitivity, but it unknown what such occur. investigate this, species focusing , CF pathogen. studied large set whether changes Based experiments, used mathematical simulate ’s colistin tobramycin presence pathogens. This study offers comprehensive data altered infections, serves foundation optimizing consolidates importance considering

Язык: Английский

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Integrated multi-omics identifies pathways governing interspecies interaction between A. fumigatus and K. pneumoniae

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Ноя. 12, 2024

Polymicrobial co- and superinfections involving bacterial fungal pathogens pose serious challenges for diagnosis therapy, are associated with elevated morbidity mortality. However, the metabolic dynamics of bacterial-fungal interactions (BFI) resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus bacterium Klebsiella pneumoniae clinically important sharing common niches in human body, especially lower respiratory tract. We have exploited an integrated multi-omics approach to unravel complex multifaceted processes implicated interspecies communication these mixed biofilms. In this setting, A. responds challenge by rewiring its metabolism, attenuating translational machineries, connecting secondary primary while K. maintains central metabolism translation activity. flexibility ability quickly adapt changing microenvironment mediated bacteria highlight new possibilities studying cross-communication between competing interaction partners. data underscore complexity governing underlying BFI, such as pronounced changes mounted interacting pneumoniae. Our findings identify candidate biomarkers potentially exploitable improved clinical management BFI.

Язык: Английский

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The Coexistence of Klebsiella pneumoniae and Candida albicans Enhanced Biofilm Thickness but Induced Less Severe Neutrophil Responses and Less Inflammation in Pneumonia Mice Than K. pneumoniae Alone

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12157 - 12157

Опубликована: Ноя. 12, 2024

Due to the possible coexistence of Klebsiella pneumoniae (KP) and Candida albicans (CA), strains KP CA with biofilm production properties clinically isolated from patients were tested. The biofilms combined organisms (KP+CA) was higher than each organism alone, as indicated by crystal violet z-stack immunofluorescence. In parallel, bacterial abundance in + similar KP, but fungal (culture method), implying that grows better presence KP. Proteomic analysis performed compare alone. With mouse neutrophils (thioglycolate induction), induced less prominent responses biofilms, determined (i) neutrophilic supernatant cytokines (ELISA) (ii) neutrophil extracellular traps (NETs), using immunofluorescent images (neutrophil elastase, myeloperoxidase, citrullinated histone 3), peptidyl arginine deiminase 4 (PAD4) expression, cell-free DNA. Likewise, intratracheal C57BL/6 mice induces severe pneumonia organ injury (serum creatinine alanine transaminase) (colorimetric assays), (ELISA), bronchoalveolar lavage fluid parameters (bacterial culture abundances a hemocytometer), histology score (H&E stains), NETs (immunofluorescence on lung tissue). conclusion, biomass mostly produced potent activation Hence, fungi respiratory tract might benefit host some situations, despite well-known adverse effects fungi.

Язык: Английский

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