Genome Sequencing Reveals Widespread Virulence Gene Exchange among Human Neisseria Species

Marri, Pradeep Reddy; Paniscus, Mary; Weyand, Nathan J.; Rendón, María A.; Calton, Christine M.; Hernández, Diana R.; Higashi, Dustin L.; Sodergren, Erica; Weinstock, George M.; Rounsley, Steven D.; So, Magdalene

doi:10.1371/journal.pone.0011835

Cited by 182 publications

(256 citation statements)

References 55 publications

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“…The 5′-atGCCGTCTGAA-3′ DUS motif (less conserved nucleotides are in lowercase) (17,25) is highly overrepresented within the genomes of all sequenced Neisseria species (on average, every kilobase), with single base variations in some of them (26). Therefore, we reasoned that, if ComP was the DUS receptor in Neisseria species, it must be conserved beyond N. meningitidis.…”

Section: Resultsmentioning

confidence: 99%

Specific DNA recognition mediated by a type IV pilin

Cehovin

Simpson

McDowell

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

149

170

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Natural transformation is a dominant force in bacterial evolution by promoting horizontal gene transfer. This process may have devastating consequences, such as the spread of antibiotic resistance or the emergence of highly virulent clones. However, uptake and recombination of foreign DNA are most often deleterious to competent species. Therefore, model naturally transformable Gramnegative bacteria, including the human pathogen Neisseria meningitidis, have evolved means to preferentially take up homotypic DNA containing short and genus-specific sequence motifs. Despite decades of intense investigations, the DNA uptake sequence receptor in Neisseria species has remained elusive. We show here, using a multidisciplinary approach combining biochemistry, molecular genetics, and structural biology, that meningococcal type IV pili bind DNA through the minor pilin ComP via an electropositive stripe that is predicted to be exposed on the filaments surface and that ComP displays an exquisite binding preference for DNA uptake sequence. Our findings illuminate the earliest step in natural transformation, reveal an unconventional mechanism for DNA binding, and suggest that selective DNA uptake is more widespread than previously thought.DNA receptor | genetic competence

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Section: Resultsmentioning

confidence: 99%

Specific DNA recognition mediated by a type IV pilin

Cehovin

Simpson

McDowell

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

149

170

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“…Human-specific commensal and pathogenic Neisseria have 896 genes in common, many of which encode virulence factors (32). N. macacae harbor orthologs of Neisseria virulence factors, putative and established (Tables S1 and S2); their contribution to colonization, long-term carriage, and transmission can be examined via in vitro experimentation followed by animal testing of defined mutants or recombinant mutant libraries.…”

Section: Discussionmentioning

confidence: 99%

Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer

Weyand

Wertheimer

Hobbs

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbehost interactions. We developed a rhesus macaque model for studying Neisseria-host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates.commensal Neisseria | nonhuman primate model | type IV pili M icrobe-host interactions are often refractory to investigation because of the exquisite tropism of many bacteria for the human host. Host-restriction has prevented the development of animal models that recapitulate colonization, transmission, and persistence; hampered studies of horizontal gene transfer (HGT); and prevented preclinical testing of vaccine candidates. One means to circumvent host restrictions is to develop an animal model of infection using a related species indigenous to that animal. For example, infections by human pathogens, such as Bordetella pertussis and Chlamydia trachomatis, have been effectively modeled in animals with Bordetella bronchiseptica and Chlamydia muridarum, respectively (1, 2).The genus Neisseria and the rhesus macaque provide us with this opportunity. Neisseria are Gram-negative, diplococcal β-Proteobacteria. This genus includes >10 human-adapted species, two of which are pathogens, and an unknown number of species that naturally colonize animals. These species are highly related: >40% of the genes in pathogenic species are also present in commensals, and many of these encode virulence genes and antibiotic resistance alleles. The species are naturally competent and transfer genetic information to each other in vitro (3, 4). HGT is widely assumed to play an important role in the spread of antibiotic resistance among pathogenic Neisseria; however, there is little information on the extent to which HGT occurs in vivo.Pathogens Neisseria meningitidis and Neisseria gonorrhoeae have an exquisite tropism for man. These pathogens do not naturally infect animals; inoculated into nonhuman hosts, the pathogens will colonize only for brief periods (5, 6). Neisseria species have been isolated from a number of animals (7-10), suggesting it may be possible to develop a model for studying Neisseria-host interactions in which there are no host-restriction barriers to overcome.The ...

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“…has been described previously. It is wellknown that this genus is naturally competent (6,63,64). Many mosaic sequences from N. meningitidis or N. gonorrhoeae and other commensal nonpathogenic members of this genus have been found (5,(65)(66)(67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

“…that are closely related. Isolates of a human pathogen of the group, Neisseria meningitidis, have been shown to contain foreign gene sequences that were first identified in commensal strains, such as Neisseria lactamica or Neisseria cinerea (4)(5)(6)(7)(8). These data are based on multilocus sequence typing (MLST) of housekeeping genes (9)(10)(11)(12)(13)(14) and multilocus enzyme electrophoresis (15).…”

mentioning

confidence: 99%

Description of an Unusual Neisseria meningitidis Isolate Containing and Expressing Neisseria gonorrhoeae-Specific 16S rRNA Gene Sequences

Walcher¹,

Skvoretz²,

Montgomery-Fullerton³

et al. 2013

J Clin Microbiol

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An apparently rare Neisseria meningitidis isolate containing one copy of a Neisseria gonorrhoeae 16S rRNA gene is described herein. This isolate was identified as N. meningitidis by biochemical identification methods but generated a positive signal with Gen-Probe Aptima assays for the detection of Neisseria gonorrhoeae. Direct 16S rRNA gene sequencing of the purified isolate revealed mixed bases in signature regions that allow for discrimination between N. meningitidis and N. gonorrhoeae. The mixed bases were resolved by sequencing individually PCR-amplified single copies of the genomic 16S rRNA gene. A total of 121 discrete sequences were obtained; 92 (76%) were N. meningitidis sequences, and 29 (24%) were N. gonorrhoeae sequences. Based on the ratio of species-specific sequences, the N. meningitidis strain seems to have replaced one of its four intrinsic 16S rRNA genes with the gonococcal gene. Fluorescence in situ hybridization (FISH) probes specific for meningococcal and gonococcal rRNA were used to demonstrate the expression of the rRNA genes. Interestingly, the clinical isolate described here expresses both N. meningitidis and N. gonorrhoeae 16S rRNA genes, as shown by positive FISH signals with both probes. This explains why the probes for N. gonorrhoeae in the Gen-Probe Aptima assays cross-react with this N. meningitidis isolate. The N. meningitidis isolate described must have obtained N. gonorrhoeae-specific DNA through interspecies recombination.

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Genome Sequencing Reveals Widespread Virulence Gene Exchange among Human Neisseria Species

Cited by 182 publications

References 55 publications

Specific DNA recognition mediated by a type IV pilin

Specific DNA recognition mediated by a type IV pilin

Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer

Description of an Unusual Neisseria meningitidis Isolate Containing and Expressing Neisseria gonorrhoeae-Specific 16S rRNA Gene Sequences

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