A chromosomally integrated bacteriophage in invasive meningococci

Abstract

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.

Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen-specific genes

“…For example, a genetic island containing a chromosomally integrated bacteriophage was found previously to be associated with 100 % of hypervirulent lineages and absent from 90 % of noninvasive isolates (Bille et al, 2005). In the current study, this island was present in 60 % of the virulent strains and 42 % of the carriage strains examined, suggesting that this phage may be a marker for certain hypervirulent clonal groups (e.g.…”

“…Some of the N. meningitidis-specific genes, core genes and pathogen-specific genes have been described previously (Bille et al, 2005;Perrin et al, 1999Perrin et al, , 2002Snyder et al, 2004Snyder et al, , 2005Snyder & Saunders, 2006;Stabler & Hinds, 2006;Stabler et al, 2005). However, the alternative methods, different microarray platforms, the breadth of strains examined, and dissimilar analysis methods lead to some differences (Table S2).…”

“…N. gonorrhoeae FA1090 (GenBank AE004969) and N. meningitidis FAM18 (http://www.sanger.ac.uk/Projects/) genome sequences are also available. Other genome-based techniques such as comparative genome hybridization (mCGH) and subtractive hybridization have addressed issues of (1) cross-species comparisons, (2) particular islands of horizontal transfer, (3) phylogeny, (4) particular regions of biological interest, and/or (5) total genomic content (Bille et al, 2005;Perrin et al, 1999Perrin et al, , 2002Snyder et al, 2004Snyder et al, , 2005Snyder & Saunders, 2006;Stabler & Hinds, 2006;Stabler et al, 2005). We sought to explore the variable gene content of N. meningitidis in an effort to understand the prevalence and importance of horizontal gene transfer within this important, naturally competent organism.…”

Topology of the outer-membrane secretin PilQ from Neisseria meningitidis

“…Likewise, the C-terminal Glu 606 RLys 606 PilQ mutant (designated the penC allele) has been found to be more permissive to antibiotics than PilQ WT strains (Zhao et al, 2005). Phage transport, as well as pilus locomotion and transmembrane flux, have been associated with the function of PilQ (Bille et al, 2005). Although the secretin C terminus has been implicated in vancomycin permeability (Schmidt et al, 2001;Wall et al, 1999), this is the first description of the role of the secretin N-terminal region in this context.…”

Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation

“…47 Finally, early detection and therapy of microbial infections are crucial determinants of HCT outcomes as 430% of HCT recipients develop an episode of bacteremia in the first weeks following transplant and 15% of all mortalities following unrelated allogeneic HCT are infection related. 5 Rapid and accurate detection, identification and drug-susceptibility phenotyping methods for isolated clinical pathogen(s) using WGS and CAS of non-human DNA or RNA 48,49 using genomic or ribosomal multi-locus sequence typing (MLST/rMLST) already exist. In one approach, for example, a Abbreviations: ALL, acute lymphoblastic leukemia; EFS, event-free survival; GC, glucocorticoids; GI, gastrointestinal; HCT, hematopoietic stem cell transplant; MRD, minimal residual disease; TRM, transplant-related mortality.…”