Case Report: Infective Endocarditis of Mechanical Aortic Valve Due to Neisseria elongata Bacteremia.

BACKGROUND Neisseria elongata is a infrequent cause of infective endocarditis (IE). Although considered a commensal bacterium of the human nasopharynx, N. elongata has been shown to be the cause of significant disease in humans, namely endocarditis, osteomyelitis, and septicemia. CASE REPORT We report the case of a 53-year-old man with a past medical history of mechanical aortic valve who presented to the hospital for evaluation of eleven days of recurrent and relapsing fevers and was admitted for severe sepsis with concern for endocarditis. Blood cultures revealed N. elongata bacteremia, and an echocardiogram did not show any vegetations, although it was limited by mechanical aortic valve shadowing. The patient recovered after six weeks of treatment with intravenous ceftriaxone and oral ciprofloxacin. CONCLUSIONS Clinicians should be aware of the possibility of the previously considered non-pathogenic N. elongata as a source of IE caused by gram-negative organisms, as it can potentially cause severe disease and multiple complications. Our case additionally highlights that IE has highly variable clinical presentations. Thus, it is essential to utilize the Duke criteria as only a clinical guide for the diagnosis of IE rather than a substitute for clinical judgment and the decision to treat a patient with suspected IE.

Genomic analysis of Neisseria elongata isolate from a patient with infective endocarditis.

Neisseria elongata is part of the commensal microbiota of the oropharynx. Although it is not considered pathogenic to humans, N. elongata has been implicated in several cases of infective endocarditis (IE). Here, we report a case of IE caused by N. elongata subsp. nitroreducens (Nel_M001) and compare its genome with 17 N. elongata genomes available in GenBank. We also evaluated resistance and virulence profiles with Comprehensive Antibiotic Resistance and Virulence Finder databases. The results showed a wide diversity among N. elongata isolates. Based on the pangenome cumulative curve, we demonstrate that N. elongata has an open pangenome. We found several different resistance genes, mainly associated with antibiotic efflux pumps. A wide range of virulence genes was observed, predominantly pilus formation genes. Nel_M001 was the only isolate to present two copies of some pilus genes and not present nspA gene. Together, our results provide insights into how this commensal microorganism can cause IE and may assist further biological investigations on nonpathogenic Neisseria spp. Case reporting and pangenome analyses are critical for enhancing our understanding of IE pathogenesis, as well as for alerting physicians and microbiologists to enable rapid identification and treatment to avoid unfavorable outcomes.

Infective endocarditis due to Neisseria elongata: A case report and literature review.

INTRODUCTION: Neisseria elongata (NE), a Gram-negative, rod-shaped organism, was previously thought to be non-pathogenic. However, in recent years it has become increasingly recognized as a rare cause of infective endocarditis. In this paper, we report a case of NE infective endocarditis and provide a review of the literature. OBJECTIVES: To describe a case of NE endocarditis, and to review the literature in search of any similar cases of this rare condition. CASE REPORT: Our patient is a 77-year-old, otherwise healthy female patient who was found to have mitral valve endocarditis with valve regurgitation. DISCUSSION: NE endocarditis is a rare condition that typically affects the left cardiac chambers and is associated with high risk of embolization. A literature review retrieved 35 other cases. CONCLUSIONS: Our report underlines the rarity of NE endocarditis, insofar as relatively few cases have been reported. The bacterium presents similarities with HACEK organisms and can potentially cause infective endocarditis.

Bacteremia Caused by Neisseria elongata in an Infective Endocarditis Patient: Case Report and Review of Literature.

BACKGROUND: Neisseria elongata (N. elongate) is a strictly aerobic and gram-negative rod bacterium which is a constituent of the commensal bacterial flora in the pharynx. Infection caused by Neisseria elongata is rarely reported. Here we describe a case of endocarditis in a patient after aortic mechanical valve replacement caused by N. elon-gate in China. METHOD: A 30-year-old man suffered infective endocarditis after aortic mechanical valve replacement. Blood cultures were positive and the organism was identified as Neisseria elongata by MALDI-TOF MS as well as the 16S rRNA sequencing. RESULT: The patient was treated with ofloxacin and meropenem. He was successfully treated with the 6-week course of antibiotic therapy. CONCLUSIONS: N. elongate endocarditis is rarely reported. Our report expands the range of infection caused by N. elongate.

Disrupted Synthesis of a Di-N-acetylated Sugar Perturbs Mature Glycoform Structure and Microheterogeneity in the O-Linked Protein Glycosylation System of Neisseria elongata subsp. glycolytica.

The genus Neisseria includes three major species of importance to human health and disease (Neisseria gonorrhoeae, Neisseria meningitidis, and Neisseria lactamica) that express broad-spectrum O-linked protein glycosylation (Pgl) systems. The potential for related Pgl systems in other species in the genus, however, remains to be determined. Using a strain of Neisseria elongata subsp. glycolytica, a unique tetrasaccharide glycoform consisting of di-N-acetylbacillosamine and glucose as the first two sugars followed by a rare sugar whose mass spectrometric fragmentation profile was most consistent with di-N-acetyl hexuronic acid and a N-acetylhexosamine at the nonreducing end has been identified. Based on established mechanisms for UDP-di-N-acetyl hexuronic acid biosynthesis found in other microbes, we searched for genes encoding related pathway components in the N. elongata subsp. glycolytica genome. Here, we detail the identification of such genes and the ensuing glycosylation phenotypes engendered by their inactivation. While the findings extend the conservative nature of microbial UDP-di-N-acetyl hexuronic acid biosynthesis, mutant glycosylation phenotypes reveal unique, relaxed specificities of the glycosyltransferases and oligosaccharyltransferases to incorporate pathway intermediate UDP-sugars into mature glycoforms.IMPORTANCE Broad-spectrum protein glycosylation (Pgl) systems are well recognized in bacteria and archaea. Knowledge of how these systems relate structurally, biochemically, and evolutionarily to one another and to others associated with microbial surface glycoconjugate expression is still incomplete. Here, we detail reverse genetic efforts toward characterization of protein glycosylation mutants of N. elongata subsp. glycolytica that define the biosynthesis of a conserved but relatively rare UDP-sugar precursor. The results show both a significant degree of intra- and transkingdom conservation in the utilization of UDP-di-N-acetyl-glucuronic acid and singular properties related to the relaxed specificities of the N. elongata subsp. glycolytica system.

Neisseria elongata endocarditis of a native aortic valve.

Neisseria elongata is a part of the common bacterial flora of the oropharynx but has caused sepsis, osteomyelitis and infective endocarditis on rare occasions. We report the case of a 56-year-old Caucasian woman who was admitted to hospital with a 5-week history of fever, malaise and fatigue. Two blood cultures grew Gram-negative rods which were confirmed to be N. elongata subspecies nitroreducens via bacterial DNA sequence analysis. An echocardiogram showed a large mobile vegetation on the right and non-coronary cusps of the aortic valve. The patient underwent aortic valve replacement and antibiotic therapy for 6 weeks. We suggest that clinicians should consider extended antibiotic treatment and early surgical evaluation based on the nature and aggressiveness of N. elongata.

Characterization of a Unique Tetrasaccharide and Distinct Glycoproteome in the O-Linked Protein Glycosylation System of Neisseria elongata subsp. glycolytica.

UNLABELLED: Broad-spectrum O-linked protein glycosylation is well characterized in the major Neisseria species of importance to human health and disease. Within strains of Neisseria gonorrhoeae, N. meningitidis, and N. lactamica, protein glycosylation (pgl) gene content and the corresponding oligosaccharide structure are fairly well conserved, although intra- and interstrain variability occurs. The status of such systems in distantly related commensal species, however, remains largely unexplored. Using a strain of deeply branching Neisseria elongata subsp. glycolytica, a heretofore unrecognized tetrasaccharide glycoform consisting of di-N-acetylbacillosamine-glucose-di-N-acetyl hexuronic acid-N-acetylhexosamine (diNAcBac-Glc-diNAcHexA-HexNAc) was identified. Directed mutagenesis, mass spectrometric analysis, and glycan serotyping confirmed that the oligosaccharide is an extended version of the diNAcBac-Glc-based structure seen in N. gonorrhoeae and N. meningitidis generated by the successive actions of PglB, PglC, and PglD and glucosyltransferase PglH orthologues. In addition, a null mutation in the orthologue of the broadly conserved but enigmatic pglG gene precluded expression of the extended glycoform, providing the first evidence that its product is a functional glycosyltransferase. Despite clear evidence for a substantial number of glycoprotein substrates, the major pilin subunit of the endogenous type IV pilus was not glycosylated. The latter finding raises obvious questions as to the relative distribution of pilin glycosylation within the genus, how protein glycosylation substrates are selected, and the overall structure-function relationships of broad-spectrum protein glycosylation. Together, the results of this study provide a foundation upon which to assess neisserial O-linked protein glycosylation diversity at the genus level. IMPORTANCE: Broad-spectrum protein glycosylation systems are well characterized in the pathogenic Neisseria species N. gonorrhoeae and N. meningitidis. A number of lines of evidence indicate that the glycan components in these systems are subject to diversifying selection and suggest that glycan variation may be driven in the context of glycosylation of the abundant and surface-localized pilin protein PilE, the major subunit of type IV pili. Here, we examined protein glycosylation in a distantly related, nonpathogenic neisserial species, Neisseria elongata subsp. glycolytica. This system has clear similarities to the systems found in pathogenic species but makes novel glycoforms utilizing a glycosyltransferase that is widely conserved at the genus level but whose function until now remained unknown. Remarkably, PilE pilin is not glycosylated in this species, a finding that raises important questions about the evolutionary trajectories and overall structure-function relationships of broad-spectrum protein glycosylation systems in bacteria.

Neisseria elongata subsp elongata infective endocarditis following endurance exercise.

A 31-year-old Argentinian woman presented with a 3-week history of fever, night sweats, myalgia and lethargy following a work trip to Uganda where she ran a marathon. Malarial screens were negative but C reactive protein, erythrocyte sedimentation rate and neutrophil count were raised and she was anaemic. A new pansystolic murmur was heard over the mitral valve and the transthoracic echocardiogram showed a large vegetation (>1 cm) with at least moderate mitral regurgitation. Blood cultures grew Neisseria elongata, subsp elongata treated initially with ceftriaxone then oral ciprofloxacin to complete 4 weeks of treatment. CT scan revealed a wedge-shaped area of low attenuation in the spleen in keeping with a splenic infarct. Seven days postadmission, the patient underwent a successful mitral valve repair. Recovery was complicated by a likely embolic infarct in the right frontal lobe, but the patient was discharged 12 days postoperative with no neurological sequelae.

[Isolation of Neisseria elongata subsp. elongata Isolated from an Acute Myelogenous Leukemia Patient].

Gram-negative cocci with a rod-like shape were isolated from a blood sample of a patient with acute myelogenous leukemia (AML). The 16S rRNA sequence of the isolate was similar to that of Neisseria elongata. Because previous reports about N. elongata as a pathogen have been extremely rare, more reliable identification seemed to be needed. We thus additionally performed a Multilocus Sequencing Analysis (MLSA) based on another four regions (argF, rho, recA, glnA), and confirmed the identification of N. elongata. The results from the MLSA identified the species; however, we could not identify the isolates into subspecies from the sequences. Three subspecies of N. elongata (N. elongata subsp. elongata, N. elongata subsp. glycolytica and N. elongata subsp. nitroreducens) were classified based on three definitive characteristics (catalase possession, nitrite reducibility, and acid from glucose). The results of the tests of three characteristics supported the identification of the isolate as N. elongata subsp. elongata. Therefore we determined the isolate from the AML patient to be N. elongata subsp. elongata.

Native valve endocarditis caused by Neisseria elongata Subsp. nitroreducens.

Neisseria elongata, a normal resident in the human oral cavity, rarely causes invasive infections. We herein report a case of endocarditis caused by Neisseria elongata subsp. nitroreducens that occurred in a patient without any apparent cardiac complications. The patient received aortic valve replacement following the administration of intravenous beta-lactam for five weeks. To our knowledge, this is the first published case in Japan of N. elongata infection in a patient without a prosthetic device.

Cytochrome c-based domain modularity governs genus-level diversification of electron transfer to dissimilatory nitrite reduction.

The genus Neisseria contains two pathogenic species (N. meningitidis and N. gonorrhoeae) in addition to a number of commensal species that primarily colonize mucosal surfaces in man. Within the genus, there is considerable diversity and apparent redundancy in the components involved in respiration. Here, we identify a unique c-type cytochrome (cN ) that is broadly distributed among commensal Neisseria, but absent in the pathogenic species. Specifically, cN supports nitrite reduction in N. gonorrhoeae strains lacking the cytochromes c5 and CcoP established to be critical to NirK nitrite reductase activity. The c-type cytochrome domain of cN shares high sequence identity with those localized c-terminally in c5 and CcoP and all three domains were shown to donate electrons directly to NirK. Thus, we identify three distinct but paralogous proteins that donate electrons to NirK. We also demonstrate functionality for a N. weaverii NirK variant with a C-terminal c-type heme extension. Taken together, modular domain distribution and gene rearrangement events related to these respiratory electron carriers within Neisseria are concordant with major transitions in the macroevolutionary history of the genus. This work emphasizes the importance of denitrification as a selectable trait that may influence speciation and adaptive diversification within this largely host-restricted bacterial genus.

Successful oral ciprofloxacin therapy of Neisseria elongata endocarditis.

OBJECTIVE: To report successful oral ciprofloxacin therapy for Neisseria elongata endocarditis. CASE SUMMARY: A patient with N elongata endocarditis refused parenteral therapy, but his infection completely resolved with 7 weeks of oral ciprofloxacin. DISCUSSION: This patient's refusal of parenteral therapy prompted the use of oral ciprofloxacin because it is well absorbed and was expected to be very active against his organism. His infection resolved and did not relapse. Although successful oral therapy has been reported for endocarditis caused by Staphylococcus aureus, primarily in injection drug users, completely oral therapy for other organisms has not been previously described. CONCLUSIONS: When parenteral therapy is not possible, oral administration of highly active, well-absorbed antibiotics may be effective for selected cases of endocarditis caused by susceptible organisms.

Infective endocarditis caused by Neisseria elongata on a native tricuspid valve and confirmed by DNA sequencing.

Neisseria elongata, a common oral bacterium, has been recognized as a cause of infections such as infective endocarditis, septicemia, and osteomyelitis. Neisseria-induced infective endocarditis, although infrequently reported, typically arises after dental procedures. Without antibiotic therapy, its complications can be severe. We report the case of a 27-year-old man who presented with fever, severe dyspnea, and a leg abscess from cellulitis. An echocardiogram showed a vegetation-like echogenic structure on the septal leaflet of the patient's native tricuspid valve, and an insignificant Gerbode defect. Three blood cultures grew gram-negative, antibiotic-susceptible coccobacilli that were confirmed to be N. elongata. Subsequent DNA sequencing conclusively isolated N. elongata subsp nitroreducens as the organism responsible for the infective endocarditis. The patient recovered after 21 days of antibiotic therapy. In addition to the patient's unusual case, we discuss the nature and isolation of N. elongata and its subspecies.