- Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and Bacterial-Host Interactions Facilitate the Bacterial Pathogen Invading the Brain. [Review]
- CMCell Mol Neurobiol 2018 Aug 16
- This review aims to elucidate the different mechanisms of blood brain barrier (BBB) disruption that may occur due to invasion by different types of bacteria, as well as to show the bacteria-host inte...
This review aims to elucidate the different mechanisms of blood brain barrier (BBB) disruption that may occur due to invasion by different types of bacteria, as well as to show the bacteria-host interactions that assist the bacterial pathogen in invading the brain. For example, platelet-activating factor receptor (PAFR) is responsible for brain invasion during the adhesion of pneumococci to brain endothelial cells, which might lead to brain invasion. Additionally, the major adhesin of the pneumococcal pilus-1, RrgA is able to bind the BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), thus leading to invasion of the brain. Moreover, Streptococcus pneumoniae choline binding protein A (CbpA) targets the common carboxy-terminal domain of the laminin receptor (LR) establishing initial contact with brain endothelium that might result in BBB invasion. Furthermore, BBB disruption may occur by S. pneumoniae penetration through increasing in pro-inflammatory markers and endothelial permeability. In contrast, adhesion, invasion, and translocation through or between endothelial cells can be done by S. pneumoniae without any disruption to the vascular endothelium, upon BBB penetration. Internalins (InlA and InlB) of Listeria monocytogenes interact with its cellular receptors E-cadherin and mesenchymal-epithelial transition (MET) to facilitate invading the brain. L. monocytogenes species activate NF-κB in endothelial cells, encouraging the expression of P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1), and Vascular cell adhesion protein 1 (VCAM-1), as well as IL-6 and IL-8 and monocyte chemoattractant protein-1 (MCP-1), all these markers assist in BBB disruption. Bacillus anthracis species interrupt both adherens junctions (AJs) and tight junctions (TJs), leading to BBB disruption. Brain microvascular endothelial cells (BMECs) permeability and BBB disruption are induced via interendothelial junction proteins reduction as well as up-regulation of IL-1α, IL-1β, IL-6, TNF-α, MCP-1, macrophage inflammatory proteins-1 alpha (MIP1α) markers in Staphylococcus aureus species. Streptococcus agalactiae or Group B Streptococcus toxins (GBS) enhance IL-8 and ICAM-1 as well as nitric oxide (NO) production from endothelial cells via the expression of inducible nitric oxide synthase (iNOS) enhancement, resulting in BBB disruption. While Gram-negative bacteria, Haemophilus influenza OmpP2 is able to target the common carboxy-terminal domain of LR to start initial interaction with brain endothelium, then invade the brain. H. influenza type b (HiB), can induce BBB permeability through TJ disruption. LR and PAFR binding sites have been recognized as common routes of CNS entrance by Neisseria meningitidis. N. meningitidis species also initiate binding to BMECs and induces AJs deformation, as well as inducing specific cleavage of the TJ component occludin through the release of host MMP-8. Escherichia coli bind to BMECs through LR, resulting in IL-6 and IL-8 release and iNOS production, as well as resulting in disassembly of TJs between endothelial cells, facilitating BBB disruption. Therefore, obtaining knowledge of BBB disruption by different types of bacterial species will provide a picture of how the bacteria enter the central nervous system (CNS) which might support the discovery of therapeutic strategies for each bacteria to control and manage infection.
- Escherichia coli causing meningitis in an adult: A case report and experimental characterization of its virulence. [Journal Article]
- EIEnferm Infecc Microbiol Clin 2018 Jul 06
- Central Nervous System Infections. [Review]
- PCPrim Care 2018; 45(3):505-518
- Infections of the nervous system are potential life-threatening and are caused by pathogens such as bacteria, viruses, and fungi. Prompt recognition and treatment of a central nervous system (CNS) in...
Infections of the nervous system are potential life-threatening and are caused by pathogens such as bacteria, viruses, and fungi. Prompt recognition and treatment of a central nervous system (CNS) infection is crucial for patient survival, as these infections have a high morbidity and mortality. CNS infections include meningitis, encephalitis, and brain abscesses. This article seeks to detail the etiology, clinical course, diagnostic challenges, and treatment of CNS infections organized by infectious agent.
- Gamma-irradiation-killed Streptococcus pneumoniae potently induces the expression of IL-6 and IL-8 in human bronchial epithelial cells. [Journal Article]
- MPMicrob Pathog 2018 Aug 13
- Streptococcus pneumoniae is a major respiratory pathogen that can cause pneumonia, meningitis, and otitis media. Although capsular polysaccharide-based vaccines are commercially available, there is a...
Streptococcus pneumoniae is a major respiratory pathogen that can cause pneumonia, meningitis, and otitis media. Although capsular polysaccharide-based vaccines are commercially available, there is a need for broad-spectrum, serotype-independent, and cost-effective vaccines. Recently, an intranasal vaccine formulated with gamma-irradiated nonencapsulated S. pneumoniae whole cells has been developed and its immunogenicity is under investigation. Since innate immunity influences the subsequent adaptive immunity, in the present study, we investigated the immunostimulatory activity of gamma-irradiated S. pneumoniae (r-SP) in the human bronchial epithelial cell-line, BEAS-2B, by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP). r-SP potently induced interleukin (IL)-6 and IL-8 at both mRNA and protein levels in a dose- and time-dependent manner, whereas h-SP and f-SP poorly induced them. Of note, the mRNA levels of IL-6 and IL-8 were approximately two-fold higher when cells were stimulated with 3 × 107 CFU/ml of r-SP for 3 h, while the protein levels of IL-6 and IL-8 were approximately five-fold higher after stimulation with 3 × 107 CFU/ml of r-SP for 24 h. Furthermore, r-SP exhibited potent activation of Toll-like receptor 2 compared with h-SP or f-SP. The expression of IL-6 and IL-8 induced by r-SP was mediated through the activation of mitogen-activated protein kinases. Remarkably, when r-SP was further treated with heat or formalin, there was a decrease in the aforementioned activities. Taken together, we suggest that r-SP stimulates the human respiratory epithelial cells to produce the cytokines IL-6 and IL-8, which might influence the induction of adaptive immune responses.
- Acute Otitis Media and Associated Complications in United States Emergency Departments. [Journal Article]
- ONOtol Neurotol 2018; 39(8):1005-1011
- CONCLUSIONS: ED visits related to AOM or mastoiditis are common and complications are rare. An in-depth analysis on a national level is useful for assessing healthcare utilization trends.
- Hypothermia: A Sign of Sepsis in Young Infants in the Emergency Department? [Journal Article]
- PEPediatr Emerg Care 2018 Aug 14
- CONCLUSIONS: The prevalence of serious infection in hypothermic young infants in the ED is low. Serious infection is unlikely in infants with isolated hypothermia.
- First reported case of naturally acquired fatal anthrax from Northeast India. [Journal Article]
- JFJ Family Med Prim Care 2018 May-Jun; 7(3):632-634
- Anthrax is a zoonotic disease and is caused by Bacillus anthracis which is a Gram-positive, nonmotile, spore-forming rod, found in soil. The spores can remain viable for decades. Transmission occurs ...
Anthrax is a zoonotic disease and is caused by Bacillus anthracis which is a Gram-positive, nonmotile, spore-forming rod, found in soil. The spores can remain viable for decades. Transmission occurs naturally in humans by direct contact with infected animals or the contaminated animal products. Anthrax is a major health problem in eastern and southern India, with a significant human incidence because the disease is poorly controlled. Here, we discuss such a case of naturally occurring fatal anthrax in North-East India. A 48-year-old man from Assam presented with seizures, hematemesis, and fever. Apart from altered mental status and nonreactive pupils, his cutaneous and systemic examination was unremarkable. Noncontrast computed tomography head showed multiple hemorrhages. Blood and cerebrospinal fluid showed heavy growth of anthrax Bacilli. He was started on specific antibiotics after the reports, but unfortunately, the patient succumbed to infection. Due to high prevalence of anthrax in the endemic regions, a high degree of suspicion is required to clinch the diagnosis. Early initiation of therapy before developing the intracranial hemorrhagic complications might result in a better outcome. Careful history for a possible exposure to animal carcass or a suspected animal death due to anthrax will also help in early diagnosis of the disease and effective therapy.
- A Case of Diffuse Leptomeningeal Glioneuronal Tumor Misdiagnosed as Chronic Tuberculous Meningitis without Brain Biopsy. [Journal Article]
- CRCase Rep Neurol Med 2018; 2018:1391943
- Here we report a rare case of diffuse leptomeningeal glioneuronal tumor (DLGNT) in a 62-year-old male patient misdiagnosed as having tuberculous meningitis. Due to its rarity and radiologic findings ...
Here we report a rare case of diffuse leptomeningeal glioneuronal tumor (DLGNT) in a 62-year-old male patient misdiagnosed as having tuberculous meningitis. Due to its rarity and radiologic findings of leptomeningeal enhancement in the basal cisterns on magnetic resonance imaging (MRI) similar to tuberculous meningitis, DLGNT in this patient was initially diagnosed as communicating hydrocephalus from tuberculous meningitis despite absence of laboratory findings of tuberculosis. The patient's symptoms and signs promptly improved after a ventriculoperitoneal shunting surgery followed by empirical treatment against tuberculosis. Five years later, mental confusion and ataxic gait developed in this patient again despite well-functioning ventriculoperitoneal shunt. Aggravation of leptomeningeal enhancement in the basal cisterns was noted in MRI. An additional course of antituberculosis medication with steroid was started without biopsy of the brain. Laboratory examinations for tuberculosis were negative again. After four months of improvement, his mental confusion, memory impairment, dysphasia, and ataxia gradually worsened. A repeated MRI of the brain showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain surface and leptomeninges revealed a very rare occurrence of DLGNT. His delayed diagnosis of DLGNT might be due to prevalence of tuberculosis in our country, similarity in MRI finding of prominent leptomeningeal enhancement in the basal cisterns, and extreme rarity of DLGNT in the elderly. DLGLT should be considered in differential diagnosis of medical conditions presenting as communicating hydrocephalus with prominent leptomeningeal enhancement. A timely histologic diagnosis through a leptomeningeal biopsy of the brain and spinal cord in case of unusual leptomeningeal enhancement with uncertain laboratory findings is essential because cytologic examination of the cerebrospinal fluid in DLGNT is known to be negative.
- Relevant analyses of pathogenic bacteria and inflammatory factors in neonatal purulent meningitis. [Journal Article]
- ETExp Ther Med 2018; 16(2):1153-1158
- Pathogenic bacteria and inflammatory factors in neonatal purulent meningitis (PM) were investigated to explore the diagnostic value of inflammatory factors in PM, to clarify the etiology, and to prov...
Pathogenic bacteria and inflammatory factors in neonatal purulent meningitis (PM) were investigated to explore the diagnostic value of inflammatory factors in PM, to clarify the etiology, and to provide evidence for rational clinical treatment. Seventy-four neonates who were diagnosed with PM and were bacteriogically positive in Daqing Longnan Hospital from January 2012 to December 2015 were retrospectively analyzed and used as observation group. Another 74 neonates simultaneously hospitalized with non-PM factors were selected as control group. The levels of C-reactive protein (CRP) and β 2 microglobulin (β2MG) in cerebrospinal fluid in pediatric patients were measured, and the separation culture and identification of pathogenic bacteria were carried out at the same time. The results showed that i) neonatal PM often lacked specific clinical manifestations; ii) high risk factors of neonatal PM included gestational age, body weight <2,500 g, neonatal asphyxia, premature rupture of membranes, and umbilical or pulmonary infection; iii) the levels of CRP and β2MG in the cerebrospinal fluid in the neonatal PM group were significantly higher than those in the control group (P<0.05), and the neonatal PM group had obviously decreased levels of CRP and β2MG in the cerebrospinal fluid after treatment compared with those before treatment (P<0.05); iv) the positive rate of Gram-negative bacilli (G-bacilli) showed an increasing trend year by year in the past 4 years. Seventy-four strains of bacteria were isolated from the cerebrospinal fluid in neonatal PM group, including 45 strains of Gram-positive cocci (G+cocci, accounting for 60.81%) and 29 strains of G-bacilli (accounting for 39.19%). Among them, the top three were Escherichia coli, coagulase-negative staphylococci (CNS) and Streptococcus. These findings indicated that for suspected PM pediatric patients with high risk factors, the inflammatory factors in cerebrospinal fluid and the etiology should be investigated via lumbar puncture as early as possible to confirm the diagnosis. Pathogenic bacteria of meningitis mainly are Escherichia coli, CNS and Streptococcus, and the characteristics of pathogenic bacteria should be considered during experiential medication. The incidence rate of PM due to Streptococcus has an upward tendency and great damage, needing to arouse high attention in clinic.
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- BMScan: using whole genome similarity to rapidly and accurately identify bacterial meningitis causing species. [Journal Article]
- BIBMC Infect Dis 2018 Aug 15; 18(1):405
- CONCLUSIONS: Identification of the bacterial meningitis pathogenic species is a critical step for case confirmation and further strain characterization. BMScan employs species-specific thresholds for previously-validated, genome-wide similarity statistics compiled from a curated reference genome collection to rapidly and accurately identify the species of uncharacterized bacterial meningitis pathogens and closely related pathogens. BMScan will facilitate the transition in public health laboratories from traditional phenotypic detection methods to whole genome sequencing based methods for species identification.