Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Elife ; 92020 12 17.
Article in English | MEDLINE | ID: mdl-33331820

ABSTRACT

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19/complications , Lymphocyte Activation , Pneumonia, Ventilator-Associated/drug therapy , Pseudomonas Infections/drug therapy , SARS-CoV-2 , T-Lymphocytes/immunology , Anti-Bacterial Agents/pharmacology , COVID-19/immunology , COVID-19/therapy , Drug Resistance, Multiple, Bacterial , Humans , Lung/microbiology , Male , Meropenem/pharmacology , Meropenem/therapeutic use , Metagenomics , Middle Aged , Piperacillin, Tazobactam Drug Combination/pharmacology , Piperacillin, Tazobactam Drug Combination/therapeutic use , Pneumonia, Ventilator-Associated/diagnostic imaging , Pneumonia, Ventilator-Associated/etiology , Pseudomonas Infections/diagnostic imaging , Pseudomonas Infections/etiology , Pseudomonas aeruginosa/isolation & purification , Recurrence , Respiration, Artificial
2.
Nat Microbiol ; 2(10): 1381-1388, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28785103

ABSTRACT

The bacterium Staphylococcus aureus is a major human pathogen for which the emergence of antibiotic resistance is a global public health concern. Infection severity, and in particular bacteraemia-associated mortality, has been attributed to several host-related factors, such as age and the presence of comorbidities. The role of the bacterium in infection severity is less well understood, as it is complicated by the multifaceted nature of bacterial virulence, which has so far prevented a robust mapping between genotype, phenotype and infection outcome. To investigate the role of bacterial factors in contributing to bacteraemia-associated mortality, we phenotyped a collection of sequenced clinical S. aureus isolates from patients with bloodstream infections, representing two globally important clonal types, CC22 and CC30. By adopting a genome-wide association study approach we identified and functionally verified several genetic loci that affect the expression of cytolytic toxicity and biofilm formation. By analysing the pooled data comprising bacterial genotype and phenotype together with clinical metadata within a machine-learning framework, we found significant clonal differences in the determinants most predictive of poor infection outcome. Whereas elevated cytolytic toxicity in combination with low levels of biofilm formation was predictive of an increased risk of mortality in infections by strains of a CC22 background, these virulence-specific factors had little influence on mortality rates associated with CC30 infections. Our results therefore suggest that different clones may have adopted different strategies to overcome host responses and cause severe pathology. Our study further demonstrates the use of a combined genomics and data analytic approach to enhance our understanding of bacterial pathogenesis at the individual level, which will be an important step towards personalized medicine and infectious disease management.


Subject(s)
Bacteremia/microbiology , Bacteremia/mortality , Genetic Variation , Host-Pathogen Interactions/genetics , Staphylococcus aureus/classification , Staphylococcus aureus/genetics , Staphylococcus aureus/pathogenicity , Virulence Factors/genetics , Bacterial Capsules/genetics , Bacterial Capsules/metabolism , Bacterial Toxins/genetics , Bacterial Toxins/toxicity , Base Sequence , Biofilms/growth & development , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Genes, Bacterial/genetics , Genome-Wide Association Study/methods , Genotype , Humans , Infection Control , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Phenotype , Risk Factors , Staphylococcal Infections/blood , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , United Kingdom , Virulence/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...