Brain abscess caused by L. monocytogenes: case study and genome characterization
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PROVIDER: PRJEB76141 | ENA |
REPOSITORIES: ENA
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Project description:Cerebral abscess is a potentially fatal neurosurgical condition, despite improvements in technology, new antimicrobial agents and modern neurosurgical instruments and techniques. I report the case of a 64-year-old woman, affected by a right frontobasal brain abscess, compressing the homolateral frontal horn of lateral ventricle, with a second mass partially occupying the right orbital cavity. She presented also with inflammatory sinusopathy involving the right maxillary, ethmoid and frontal sinuses. After 14 d of clinical observation and antimicrobial therapy, the patient received a computed tomography scan, which showed growth of the cerebral mass, with a ring of peripheral contrast enhancement and surrounding edema. She promptly underwent neurosurgical treatment and recovered well, except for the sight in her right eye, which remained compromised, as before the operation. This is believed to be the first case of cryptogenic cerebral abscess caused by Raoultella ornithinolityca isolated from the brain, with more than 1-year follow-up.
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Project description:Staphylococcus aureus is a major contributor of healthcare-associated infections and able to withstand numerous frequently used antibiotics. In order to develop novel treatment approaches, a deeper understanding of the complex interaction between host and pathogen is required. This is particularly true for the processes during development of tissue abscesses, which are important contributors to acute and persistent staphylococcal infections. Notably, the formation of staphylococcal abscesses takes place in distinct stages. Consequently, studies aiming to elucidate the underlying mechanisms of abscess development have to take temporal and spatial components into account. State-of-the-art proteomic technologies offer insight into complex biological systems. However, the pairing of spatial information and deep proteomic analysis is challenging, complicating the targeted analysis of relatively small-scale and heterogeneous structures like organ abscesses. To overcome existing technical limitations, we have previously introduced the use of a spatially targeted liquid extraction surface analysis (LESA) workflow termed “microLESA”. In our current study, we perform microLESA to investigate the processes at the host-pathogen interface during development of staphylococcal kidney abscesses in a murine model of systemic infection. For this investigation, regions from the abscess community, the interface surrounding the abscess, and the cortex of infected kidneys were extracted and analyzed at both 4- and 10-days post infection. By defining the proteome of different abscess regions across the course of infection, we followed the immune response and bacterial contribution to abscess development through spatial and temporal proteomic changes. The information gathered was then mapped through pathway analysis to characterize the metabolic processes at the host-pathogen interface during staphylococcal infection.
2020-11-30 | PXD019920 | Pride
Project description:Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils.
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Project description:Listeria monocytogenes strain:LMJF5203 | isolate:bovine rhombencephalitic cilinical case Genome sequencing
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Project description:Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils. Lesional skin biopsies obtained from C57BL/6J WT mice or IL-1R-deficient mice at 4 hours post-infection with Staphylococcus aureus. Uninfected skin biopsies were also collected from WT and IL-1R-deficient mice.
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Project description:Listeria monocytogenes SigB and PrfA are pleiotropic regulators of stress response and virulence gene expression, which have been shown to co-regulate genes in L. monocytogenes. We performed whole genome transcriptional profiling in the presence of PrfA* and active SigB, to identify the overlaps between the PrfA virulence regulon and the SigB stress response regulon. In L. monocytogenes, the PrfA* allele contributes to the activation of virulence genes to a level comparable to that of intracellular growing L. monocytogenes. Our results showed that the core PrfA regulon consists of 12 genes previously described as PrfA regulated. Furthermore, we found that the role of SigB during virulence gene regulation changes, dependent on the presence or absence of PrfA*. In the absence of PrfA*, SigB activated the transcription of virulence genes such as inlA and inlB. In the presence of PrfA*, SigB negatively influenced the transcription of genes in the PrfA core regulon. The observed effect of SigB on the transcript level of PrfA regulated genes was shown to reduce the cytotoxic effect of the PrfA* allele in HepG-2 cells. Our results indicate that the SigB-PrfA regulatory network is important for the adjustment of virulence gene transcription to ensure L. monocytogenes success as an intracellular pathogen. Keywords: comparison of gene expression of regulatory mutants
2008-10-01 | GSE11347 | GEO
Project description:Nocardia brain abscess is relatively rare and generally occurs in immunodeficient patients. Here, we present the first case of brain abscess due to Nocardia brevicatena in an immunocompetent patient, with unknown origin. In this case, a 49-year-old man was admitted to our hospital with limb twitching and complained of a history of intermittent headache. He was diagnosed with brain abscess through brain imaging and cured after craniotomy for abscess excision and targeted antibiotic treatment. Surgical specimens were sent for further detection. The causative organism was identified by weak acid-fast staining, culture and metagenomic next-generation sequencing (mNGS). We hope this case could provide a reference for incoming patients as well as their clinical management.
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