ArticlePLoS pathogens2019
Twin arginine translocation, ammonia incorporation, and polyamine biosynthesis are crucial for Proteus mirabilis fitness during bloodstream infection.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
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- Proteus faecis: a potentially pathogenic bacterium isolated from the freshwater Yangtze finless porpoise.Antonie van Leeuwenhoek · 2024Article
- Determinants of bacterial survival and proliferation in blood.FEMS microbiology reviews · 2024Review
- Antibiotic resistance and virulence profiles of Proteus mirabilis isolated from broiler chickens at abattoir in South Africa.Veterinary medicine and science · 2024Article
- Overview ofFrontiers in microbiology · 2024Review
- Organ agar serves as physiologically relevant alternative forInfection and immunity · 2023Article
- Klebsiella pneumoniae causes bacteremia using factors that mediate tissue-specific fitness and resistance to oxidative stress.PLoS pathogens · 2023Article
- Preferential catabolism of l- vs d-serine by Proteus mirabilis contributes to pathogenesis and catheter-associated urinary tract infection.Molecular microbiology · 2022Article
- Structural and biochemical characterisation of the Providencia stuartii arginine decarboxylase shows distinct polymerisation and regulation.Communications biology · 2022Article
- The temperature-dependent expression of type II secretion system controls extracellular product secretion and virulence in mesophilicFrontiers in cellular and infection microbiology · 2022Article
- Two Phenotypes ofInfection and drug resistance · 2022Article
- Article
- Catalase Activity is Critical for Proteus mirabilis Biofilm Development, Extracellular Polymeric Substance Composition, and Dissemination during Catheter-Associated Urinary Tract Infection.Infection and immunity · 2021Article
- Refined Quantification of Infection Bottlenecks and Pathogen Dissemination with STAMPR.mSystems · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The Gram-negative bacterium Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTI), which can progress to secondary bacteremia. While numerous studies have investigated experimental infection with P. mirabilis in the urinary tract, little is known about pathogenesis in the bloodstream. This study identifies the genes that are important for survival in the bloodstream using a whole-genome transposon insertion-site sequencing (Tn-Seq) approach. A library of 50,000 transposon mutants was utilized to assess the relative contribution of each non-essential gene in the P. mirabilis HI4320 genome to fitness in the livers and spleens of mice at 24 hours following tail vein inoculation compared to growth in RPMI, heat-inactivated (HI) naïve serum, and HI acute phase serum. 138 genes were identified as ex vivo fitness factors in serum, which were primarily involved in amino acid transport and metabolism, and 143 genes were identified as infection-specific in vivo fitness factors for both spleen and liver colonization. Infection-specific fitness factors included genes involved in twin arginine translocation, ammonia incorporation, and polyamine biosynthesis. Mutants in sixteen genes were constructed to validate both the ex vivo and in vivo results of the transposon screen, and 12/16 (75%) exhibited the predicted phenotype. Our studies indicate a role for the twin arginine translocation (tatAC) system in motility, translocation of potential virulence factors, and fitness within the bloodstream. We also demonstrate the interplay between two nitrogen assimilation pathways in the bloodstream, providing evidence that the GS-GOGAT system may be preferentially utilized. Furthermore, we show that a dual-function arginine decarboxylase (speA) is important for fitness within the bloodstream due to its role in putrescine biosynthesis rather than its contribution to maintenance of membrane potential. This study therefore provides insight into pathways needed for fitness within the bloodstream, which may guide strategies to reduce bacteremia-associated mortality.
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