A chromosomally integrated bacteriophage in invasive meningococci

Cerebrospinal meningitis is a feared disease that can cause the death of a previously healthy individual within hours. Paradoxically, the causative agent, Neisseria meningitidis, is a common inhabitant of the human nasopharynx, and as such, may be considered a normal, commensal organism. Only in a small proportion of colonized people do the bacteria invade the bloodstream, from where they can cross the blood–brain barrier to cause meningitis. Furthermore, most meningococcal disease is caused by bacteria belonging to only a few of the phylogenetic groups among the large number that constitute the population structure of this genetically variable organism. However, the genetic basis for the differences in pathogenic potential remains elusive. By performing whole genome comparisons of a large collection of meningococcal isolates of defined pathogenic potential we brought to light a meningococcal prophage present in disease-causing bacteria. The phage, of the filamentous family, excises from the chromosome and is secreted from the bacteria via the type IV pilin secretin. Therefore, this element, by spreading among the population, may promote the development of new epidemic clones of N. meningitidis that are capable of breaking the normal commensal relationship with humans and causing invasive disease

Age-related glomerulosclerosis and interstitial fibrosis in Milan normotensive rats: A podocyte disease

Age-related glomerulosclerosis and interstitial fibrosis in Milan normotensive rats: A podocyte disease. In Milan normotensive (MNS) rats glomerulosclerosis and interstitial fibrosis develop spontaneously in the absence of hypertension. Renal changes were sequentially assessed in these rats between 2 and 10 months of age. At 10 months, rats were characterized by heavy proteinuria, increased serum creatinine, focal or global glomerulosclerosis in 51 ± 12% of the glomeruli as well as tubulointerstitial injury involving > 25% of the section area. Cell injury in podocytes (evidenced as increased expression of desmin and by electron microscopy) and interstitial fibroblasts (increased expression of α-smooth muscle actin) and mild glomerular hypertrophy were witnessed as early as three to four months of age and preceded glomerulosclerosis and interstitial fibrosis. Only minor evidence of mesangial cell activation (as assessed by glomerular de novo α-smooth muscle actin or type I collagen expression or increased cell proliferation) was noted throughout the observation period. Later stages of the disease were characterized by glomerular and/or tubulointerstitial macrophage influx and osteopontin expression (a chemoattractant), mild accumulation of lymphocytes, platelets, fibrinogen, as well as by a progressive accumulation of various matrix proteins. Progressive renal disease in MNS rats is thus noteworthy for the relative lack of mesangial cell activation. Rather, early podocyte damage, induced by yet unknown mechanisms, may underlie the development of glomerulosclerosis and subsequent interstitial fibrosis

Alpha-gal syndrome – A case report of tick-borne anaphylactic shock

The most common cause of vasoplegic shock in critical care is sepsis. However, although rarely and only in specifically sensitised individuals previously bitten by a tick, red meat may provoke a delayed allergic reaction called an alpha-gal syndrome. We present a case of a protracted life-threatening manifestation of alpha-gal syndrome, which, due to an unusual absence of typical features of anaphylaxis can masquerade as septic shock and calls attention to the premature diagnostic closure as a contributor to diagnostic error. Alpha-gal syndrome is a relatively new, but increasingly recognised health issue. We propose that alpha-gal syndrome should be considered in the differential diagnosis of vasoplegic shock of unclear aetiology even in the absence of typical allergic symptomatology and typical allergen exposure since alpha-gal is present in a wide variety of carriers

Long-term evolution of antigen repertoires among carried meningococci

Most studies of bacterial pathogen populations have been based on isolates collected from individuals with disease, or their contacts, over short time periods. For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure. Here, we use mathematical models to analyse the structuring and dynamics of three vaccine-candidate antigens among carried meningococcal isolates collected over nearly 30 years in the Czech Republic. The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination. We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships

emm typing and validation of provisional M types for group A streptococci.

This report discusses the following issues related to typing of group A streptococci (GAS): The development and use of the 5' emm variable region sequencing (emm typing) in relation to the existing serologic typing system; the designation of emm types in relation to M types; a system for validation of new emm types; criteria for validation of provisional M types to new M-types; a list of reference type cultures for each of the M-type or emm-type strains of GAS; the results of the first culture exchange program for a quality control testing system among the national and World Health Organization collaborating centers for streptococci; and dissemination of new approaches to typing of GAS to the international streptococcal community

Influence of the combination and phase variation status of the haemoglobin receptors HmbR and HpuAB on meningococcal virulence

Neisseria meningitidis can utilize haem, haemoglobin and haemoglobin–haptoglobin complexes as sources of iron via two TonB-dependent phase variable haemoglobin receptors, HmbR and HpuAB. HmbR is over-represented in disease isolates, suggesting a link between haemoglobin acquisition and meningococcal disease. This study compared the distribution of HpuAB and phase variation (PV) status of both receptors in disease and carriage isolates. Meningococcal disease (n = 214) and carriage (n = 305) isolates representative of multiple clonal complexes (CCs) were investigated for the distribution, polyG tract lengths and ON/OFF status of both haemoglobin receptors, and for the deletion mechanism for HpuAB. Strains with both receptors or only hmbR were present at similar frequencies among meningococcal disease isolates as compared with carriage isolates. However, >90 % of isolates from the three CCs CC5, CC8 and CC11 with the highest disease to carriage ratios contained both receptors. Strains with an hpuAB-only phenotype were under-represented among disease isolates, suggesting selection against this receptor during systemic disease, possibly due to the receptor having a high level of immunogenicity or being inefficient in acquisition of iron during systemic spread. Absence of hpuAB resulted from either complete deletion or replacement by an insertion element. In an examination of PV status, one or both receptors were found in an ON state in 91 % of disease and 71 % of carriage isolates. We suggest that expression of a haemoglobin receptor, either HmbR or HpuAB, is of major importance for systemic spread of meningococci, and that the presence of both receptors contributes to virulence in some strains

The Effect of Immune Selection on the Structure of the Meningococcal Opa Protein Repertoire

The opa genes of the Gram negative bacterium Neisseria meningitidis encode Opacity-associated outer membrane proteins whose role is to promote adhesion to the human host tissue during colonisation and invasion. Each meningococcus contains 3–4 opa loci, each of which may be occupied by one of a large number of alleles. We analysed the Opa repertoire structure in a large, well-characterised collection of asymptomatically carried meningococci. Our data show an association between Opa repertoire and meningococcal lineages similar to that observed previously for meningococci isolated from cases of invasive disease. Furthermore, these Opa repertoires exhibit discrete, non-overlapping structure at a population level, and yet low within-repertoire diversity. These data are consistent with the predictions of a mathematical model of strong immune selection upon a system where identical alleles may occupy different loci

Tick-borne encephalitis virus in dogs - is this an issue?

The last review on Tick-borne encephalitis (TBE) in dogs was published almost ten years ago. Since then, this zoonotic tick-borne arbovirus has been geographically spreading and emerging in many regions in Eurasia and continues to do so. Dogs become readily infected with TBE virus but they are accidental hosts not capable to further spread the virus. They seroconvert upon infection but they seem to be much more resistant to the clinical disease than humans. Apart from their use as sentinels in endemic areas, however, an increasing number of case reports appeared during the last decade thus mirroring the rising public health concerns. Owing to the increased mobility of people travelling to endemic areas with their companion dogs, this consequently leads to problems in recognizing and diagnosing this severe infection in a yet non-endemic area, simply because the veterinarians are not considering TBE. This situation warrants an update on the epidemiology, clinical presentation and possible preventions of TBE in the dog