Introduction
Neisseria sicca (N. sicca) typically exists as a commensal bacterium on the mucosal surface of the human upper respiratory tract (URT), with an overall oropharyngeal carriage rate of approximately 9.4%.1 However, in recent years, with an increasing number of clinical case reports on N. sicca, it has gradually exhibited its characteristics as an opportunistic pathogen rather than just a commensal bacterium on the mucosal surface. Similar to N. meningitidis and N. gonorrhoeae, its pathogenicity may involve a series of sequential steps, including adhesion to mucosal epithelial cells, invasion of host tissues, evasion of immune defenses, and induction of inflammatory damage.2,3 This bacterium has been reported as a cause of various human infections, including endocarditis,4,5 pneumonia,6,7 sinusitis,8 osteomyelitis,9 meningitis,10 conjunctivitis,11 peritonitis,12,13 and bloodstream infections (BSIs).14,15
BSIs are systemic inflammatory response syndromes caused by the invasion of pathogenic microorganisms such as bacteria or fungi into the bloodstream.16 BSIs are associated with high mortality and increased healthcare costs.16 These infections occur not only in immunocompromised individuals but also in healthy populations. Infectious endocarditis can serve as a nidus for ongoing BSIs because microorganisms colonizing the heart valves continuously disseminate into the bloodstream.17 This may exacerbate BISs, leading to a vicious cycle of infection and inflammation. Based on the previous literature regarding infections caused by N. sicca, endocarditis constitutes the majority of cases.18 Therefore, detection of N. sicca in the bloodstream warrants vigilance for potential endocardial diseases.
In a decade-long review of ~8,000 bacteremia cases, Feder et al identified only one N. sicca-positive culture that was ultimately deemed a contaminant.19 While BSIs caused by N. sicca are uncommon, sporadic cases have been reported. Shaw et al first reported a case of N. sicca endocarditis in a 12-year-old patient.20 Subsequent studies have also described true BSIs caused by this organism, though such occurrences remain uncommon.5,18,21 These reports suggest N. sicca possesses greater pathogenic potential than is traditionally recognized.
Severe cardiac valve degeneration, including stenosis and regurgitation, often necessitates artificial valve replacement, yet this intervention carries a markedly increased risk for BSIs and endocarditis. Previous studies have reported BSI rates of ~8% after valve repair or replacement, of which 13–14.3% subsequently develop endocarditis.22,23 Following aortic valve replacement (AVR), BSIs occur in approximately 10.1% of patients, of which nearly 40% progress to endocarditis.24 The predominant causative organisms include gram-positive cocci—such as viridans group streptococci, β-hemolytic streptococci, coagulase-negative staphylococci (CoNS), methicillin-sensitive Staphylococcus aureus (MSSA), and Enterococcus spp.—and gram-negative bacilli, including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.24 Recent reports have also documented rare cases of Neisseria elongata endocarditis in patients with AVR.25,26
In this study, we report a rare case of BSIs caused by the N. sicca strain junzhu_1 of unknown origin in a patient with a seven-year history of AVR. Whole-genome sequencing was performed to gain a deeper understanding of its pathogenicity and antimicrobial resistance. This case underscores the importance of recognizing N. sicca as an opportunistic pathogen in clinical settings.
Materials and Methods
Bacteria Isolation and Identification
Blood samples were inoculated into both aerobic and anaerobic blood culture bottles, and subsequently incubated in a BACT/ALERT 3D blood culture system (bioMérieux, France). Once a positive result was obtained, Gram staining was performed directly from the bottle, and the broth was plated onto 5% sheep blood agar. The agar plates were then incubated at 37°C for 18–24 hours. The bacterial isolate was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) (bioMérieux, France) with 99.99% confidence. 16S rRNA-based taxonomic confirmation was performed by extracting and analyzing the corresponding genomic sequences from whole-genome assemblies using barrnap (https://github.com/tseemann/barrnap) with default parameters.
Antibiotic Susceptibility Assay
Antibiotic sensitivity testing was performed using the encompassed ten antibiotics: amoxicillin-clavulanate, ampicillin, tetracycline, cefotaxime, cefuroxime, rifampin, trimethoprim-sulfamethoxazole, chloramphenicol, cefaclor, and ofloxacin. MIC values were determined using ATB HAEMO CLSI (12) strips (bioMérieux, France) in accordance with the manufacturer’s guidelines, and susceptibility was interpreted based on the breakpoints outlined in the US Clinical and Laboratory Standards Institute (CLSI) M100-S34 (2024) standards. Furthermore, the Kirby (K-B) disk diffusion method was employed to test for azithromycin and erythromycin.
Public Sequence Data
Whole-genome sequences of N. sicca were retrieved from GenBank using the search term “Neisseria sicca” with a genome length restriction of 1–10 Mb, yielding 28 available strains. Following a comprehensive evaluation of assembly metrics and annotation status, we selected 22 high-quality genomes for downstream comparative genomic analysis.
Whole Genome Sequencing and Bioinformatics Analysis
Total DNA of the N. sicca junzhu_1 isolate was extracted from pure cultures using a bacterial DNA extraction kit (Bacterial/Fungal DNA Extraction Kit [Magnetic Beads], China). A next-generation sequencing library was prepared using the NEBNext®Ultra™ DNA Library Prep Kit for Illumina (NEB, USA) (350 bp fragment library, paired-end) in accordance with the manufacturer’s recommendations. The whole-genome sequence of N. sicca was obtained using the Illumina HiSeq 4000-PE150 platform (Illumina, Inc., USA), followed by assembly using Unicycler v. 0.5.0 (https://github.com/rrwick/Unicycler). The genome was annotated using the Prokaryotic Genome Annotation tool (Prokka v.1.14.6) (https:// github.com/ tseemann/prokka).
Antimicrobial Resistance and Virulence Analysis
We identified virulence and antibiotic resistance factors using the Virulence Factor Database (VFDB) (http://www.mgc.ac.cn/VFs/) and the Comprehensive Antibiotic Research Database (CARD) (https://card.mcmaster.ca/).
Phylogenetic Analysis
To characterize the evolutionary relationships among the 23 N. sicca isolates in a global context, we utilized CSI Phylogeny 1.4 for phylogenetic analyses (https://cge.food.dtu.dk/services/CSIPPhylogeny/). The phylogenetic tree was visualized and modified using iTOL (https://itol.embl.de).
Result
Case Presentation
A 73-year-old female with a 7-year history of AVR was admitted on November 8, 2023, with a one-day history of chills and high fever. Laboratory tests revealed a white blood cell (WBC) count of 17.1 × 109/L with neutrophilia (85.6%), markedly elevated C-reactive protein (CRP, 160.6 mg/L), and elevated procalcitonin (PCT, 1.53 ng/mL). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Mycoplasma pneumoniae tests were negative. Cytokine analysis showed significantly elevated interleukin-6 (IL-6, 566.10 pg/mL) and interleukin-10 (IL-10, 3888.73 pg/mL). Sputum cultures revealed normal respiratory flora, including N. sicca (1+). Blood culture yielded N. sicca, and chest computed tomography (CT) revealed an infectious lesion in the right lung (Figure 1A and D). The patient was diagnosed with pneumonia and bacteremia. The patient was administered ticarcillin-clavulanate (3.2 g q8h, IV). After one week of treatment, the patient no longer had fever, cough, or sputum production. Follow-up chest CT indicated resolution of the infectious lesion in the right upper lung (Figure 1B). Oral amoxicillin-clavulanate therapy was continued for 4 days after discharge.
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Figure 1 CT imaging changes between the two hospital admissions. (A) Local infectious lesion in upper lobe of right lung (red arrow); (B) Infectious lesion absorption in upper lobe of the right lung; (C) No infectious lesions in right upper lung lobe; (D) Plain transverse image of mediastinal window.
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On December 11, 2023, the patient was readmitted to our hospital because of persistent high fever accompanied by chills for a day. Upon presentation, the patient had a body temperature of 39.1°C, a heart rate of 97 beats per minute, and a blood pressure of 113/53 mmHg. No symptoms of cough, sputum production, chest tightness, or shortness of breath were observed. Both lungs exhibited clear respiratory sounds, with no audible rales. The abdomen was soft and non-tender without rebound pain, and the liver and spleen were not palpable. The patient denied any symptoms, such as abdominal pain, diarrhea, urinary frequency, urgency, or dysuria. CT revealed multiple small nodules in both lungs with no inflammatory lesions (Figure 1C). Transthoracic echocardiography (TTE) revealed valvular dysfunction and aortic valve replacement with no vegetation (Figure 2).
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Figure 2 Echocardiogram showed no vegetation on the valves. (A) The artificial aortic valve image (red arrow); (B) The left ventricular long-axis section image; (C) Apical precordial four chamber view of the first admission; (D) Apical precordial four chamber view of the second admission.
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Laboratory tests showed a WBC count of 13.5 ×109/L, neutrophil ratio of 80.8%, hemoglobin of 109 g/L, platelet count of 129 × 109/L, CRP of 158.0 mg/L, troponin I of 0.034 ng/mL, brain natriuretic peptide (BNP) of 795 ng/L, and PCT of 8.10 ng/mL. Tests for SARS-CoV-2, influenza A virus, adenovirus, respiratory syncytial virus, and influenza B virus antigens were all negative. Prior to initiating empiric antimicrobial treatment with ticarcillin-clavulanate (3.2 g q8h IV) for eight days, two sets of aerobic and anaerobic blood cultures were performed. On the following day, sputum culture showed normal respiratory flora, and four culture bottles were positive for gram-negative Diplococcus (Figure 3A, B and D). The organism grew on blood agar as irregular, elevated, smooth, dry, opaque, and yellowish colonies (Figure 3C). The isolated organism (N. sicca junzhu_1) was identified using MALDI-TOF MS and verified using 16S rRNA sequencing. Sepsis was diagnosed on the basis of the presence of this organism in the bloodstream. Antibiotic sensitivity testing indicated sensitivity to the current antibiotics, and the treatment was continued (Table 1).
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Table 1 MIC Values (µg/Ml) of N. Sicca Junzhu_1
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Figure 3 General overview of Neisseria sicca. (A and B) Growth curve of N. sicca under anaerobic (A) and microaerobic (B) conditions, respectively. (C) Columbia blood agar plate with growth of N.sicca. (D) Staining revealed Gram-negative diplococcus.
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After 8 days of treatment, the patient showed overall improvement with no fever or other symptoms. Follow-up blood culture results were negative. Pre-discharge blood tests showed a WBC count of 6.6×109/L with a neutrophil ratio of 71.9%, CRP of 55.3 mg/L, and PCT of 0.99 ng/mL. The patient was discharged with instructions to continue oral amoxicillin-clavulanate for one week and to follow up regularly in the outpatient clinic. During the 18-month post-discharge follow-up period, the patient remained afebrile with no recurrence of cough or other infectious symptoms.
General Genomic Features of N. sicca Junzhu_1
The genome of N. sicca junzhu_1 comprises 2,420,190 bp and exhibits a G+C content of 51.21%. The strain was predicted to have 68 contigs, 2129 coding sequences (CDSs), and 61 RNA genes [58 tRNAs, one 5S rRNA, one 16S rRNA, and one 23S rRNA]. The genome sequence of N. sicca junzhu_1 has been deposited in NCBI GenBank under the accession number SRR29061210.
The Antimicrobial Resistance of N. sicca Junzhu_1
N. sicca junzhu_1 is susceptible to a variety of antimicrobial agents including amoxicillin-clavulanate, ampicillin, tetracycline, cefotaxime, cefuroxime, rifampin, trimethoprim-sulfamethoxazole, chloramphenicol, cefaclor, and ofloxacin. However, the strain was resistant to azithromycin and erythromycin (Table 1). Consistent with these findings, the resistome of N. sicca junzhu_1 comprised three antimicrobial resistance genes: macB, macA, and mtrD (Figure 4).
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Figure 4 Distribution of antimicrobial resistance genes among 23 N. sicca isolates. Green rectangles indicate the presence of resistance genes in the corresponding isolates.
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Virulence Genes in N. sicca Junzhu_1
Virulence gene analysis showed that the pathogenicity of N. sicca junzhu-1 was related to the MntABC pathway (mntB and mntC), efflux pump system (farA, farB, mtrD, and mtrE), oxidative damage (msrA/B [pilB]), lipooligosaccharide synthesis pathway (rfaF and rfaC), membrane receptor (hpuB), motor protein (pilT), catalase (KatA), and DNA repair(recN), which may be related to the poor prognosis of infection.
Phylogenetic Analysis of 23 N. sicca Strains
To elucidate the phylogenetic relationships between Neisseria strains from different regions and our strain, junzhu_1, 22 genomic datasets from the NCBI database (Table S1), and the sequence of junzhu_1 were used to construct a phylogenetic tree. These isolates were primarily distributed in the USA (17, accounting for 73.91%), and the majority of hosts from which they were isolated were humans (n=19, 82.61%). The isolates were obtained from various samples, including oral cavity, nasopharynx, blood, urine, and duodenal aspirates. Phylogenetic analysis revealed that the two strains most closely related to the isolated strain junzhu_1 were GCA_007673275 and GCA_017753665. Strain GCA_017753665 was recovered from a blood sample in Zhejiang, China, and differed by 3585 single nucleotide polymorphisms (SNPs) in the same region (Figure 5).
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Figure 5 Recombination-filtered core genome phylogeny for a total of 23 Neisseria sicca isolates worldwide deposited in the NCBI GenBank database. The isolation date, host, source and country are represented by squares of different colors. The isolate junzhu_1 recovered in this study is highlighted in red font.
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Discussion
This case report presents a patient with a history of AVR who was confirmed to be infected with N. sicca, the origin of the infection remains elusive.
Upon admission, the patient presented with a localized inflammatory lesion in the right lung lobe, as revealed by chest CT. Blood cultures were positive for N. sicca, whereas sputum cultures revealed the presence of normal upper respiratory tract flora, including N. sicca. Unfortunately, bronchoalveolar lavage fluid was not obtained from the bacterial culture. While the exact cause of the lesion is uncertain, N. sicca infection is a possible contributor, as it has been reported to cause pneumonia in prior cases.6,7 Following antibiotic treatment, the pulmonary lesion resolved completely and the patient’s temperature normalized. However, the patient was readmitted one month later with fever, and subsequent blood cultures again detected N. sicca, CT imaging showed no pulmonary or other lesions. Comparative echocardiography from both admissions showed no evidence of vegetation on the cardiac valves.
Diagnosing prosthetic valve endocarditis is challenging and requires multiple imaging techniques beyond standard microbiological analysis.27 The complexity arises from device-related infection characteristics, biofilm formation, and limitations in imaging interpretation.27,28 Considering the possibility of infective endocarditis, a negative TTE result does not definitively exclude the diagnosis, as vegetations may be too small, located in atypical positions, or obscured by suboptimal image quality. Therefore, transesophageal echocardiography (TEE) should be considered, alongside other diagnostic modalities such as cardiac CT or PET/CT, to confirm or rule out occult infective endocarditis.29
To our knowledge, only two cases of BSIs caused by N. sicca following AVR have been reported. Cheng et al30 described a male patient with a history of AVR who presented with 10-day fever. Although TTE was negative for vegetation, TEE revealed vegetation on the aortic valve. The isolated N. sicca was found to be sensitive to meropenem, trimethoprim-sulfamethoxazole, chloramphenicol, and minocycline, but resistant or insensitive to penicillin, azithromycin, ciprofloxacin, and cefuroxime. After an 8-week treatment regimen, the patient’s blood cultures were negative, and the follow-up TEE showed no evidence of vegetation. Locke et al31 reported the case of a female patient with a history of AVR and pacemaker implantation who presented with recurrent fever. Although TTE was negative, TEE revealed two vegetations in the lead of the right atrial pacemaker. The patient subsequently underwent complete pacemaker and lead extraction, received initial intravenous ertapenem, and was later transitioned to ceftriaxone. The patient fully recovered and was discharged after completing a 6-week course of intravenous cefuroxime at home.
We retrieved 22 N. sicca sequences from GenBank and analyzed them together with the strain junzhu_1 from this study. Most strains were of human origin (n = 19), followed by environmental sources (n = 3), with one strain of unknown origin, suggesting that N. sicca can inhabit both human hosts and environmental niches. Within humans, it primarily colonizes the upper respiratory tract but has also been isolated from blood, the gastrointestinal tract, and urine. Notably, two bloodstream-derived strains were identified, including junzhu_1 and NS20201025 (GCA_017753665.1). Phylogenetic analysis revealed that NS20201025, one of the closest relatives of junzhu_1, was isolated from Zhejiang—the same geographic region as our strain. This strain has been reported to cause native-valve endocarditis complicated by multiple embolic cerebral infarctions in a patient with underlying heart disease. Collectively, these findings suggest that the strain junzhu_1 may have pathogenic potential for infective endocarditis.
In the present study, we performed whole-genome sequencing of the isolated N. sicca junzhu-1 strain to further study its pathogenicity and resistance. N.sicca junzhu-1 harbors virulence factors, including fatty acid efflux system genes (MtrCDE and FarAB-MtrE), Type IV pili (PilT), lipooligosaccharides (involving rfaC and rfaF genes), and reactive oxygen species (ROS) defense mechanisms (involving Recn, KatA, MntABC, and MsrA/B). These virulence genes are also present in the genomes of pathogenic N. gonorrhoeae and N. meningitidis and may contribute to poor infection prognosis.
MtrCDE and FarAB-MtrE efflux pumps enhance resistance against host-derived long-chain fatty acids by relying on the outer membrane protein MtrE for export. The expression of these pumps may be differentially regulated by the transcriptional regulatory protein MtrR.32 Type IV pili (TFP) are crucial for bacterial attachment to host cells, with PilT proteins mediating retraction and intimate attachment.33 Lipooligosaccharides (LOS) are key virulence factors that are involved in immune evasion, tissue attachment, and host cell invasion. Its biosynthesis involves branched oligosaccharide production linked to lipid A via two 3-deoxy-D-manno-2-octulosonic acid (KDO) molecules, with rfaC and rfaF playing essential roles.34 ROS play crucial roles in bacterial physiology and stress responses. Both N. meningitidis and N. gonorrhoeae possess ROS defense mechanisms essential for survival. These include RecN (a putative zinc metalloprotease), KatA (catalase), MntABC (an ABC-type Mn transporter), and MsrA/B (methionine sulfoxide reductases), which collectively contribute to ROS detoxification.35 Płaczkiewicz et al36 demonstrated that both N. gonorrhoeae and N. sicca induce the secretion of pro-inflammatory cytokines, including IL-6 and TNF-α, as well as chemokines CXCL8 and CCL20, in infected epithelial cells. A study37 found that commensal species of Neisseria, specifically N. sicca and N. lactamica, can cause toxic damage to cultured human endothelial cells. Considering the virulence factors of N. sicca and its ability to elicit inflammatory responses, a potential link exists between its pathogenicity and its ability to cause BSIs.
Recent research suggests that commensal Neisseria species serve as reservoirs for antibiotic resistance genes, particularly those conferring resistance to azithromycin and erythromycin, which can be horizontally transferred to pathogenic Neisseria species.38 Consistent with this, N. sicca junzhu_1 harbored resistance determinants-including macB, macA, and mtrD-that are associated with resistance to both azithromycin and erythromycin. N. lactamica harbors mutated gyrA and penA, leading to resistance to quinolones and penicillin, respectively.39 One study found that the blaTEM gene, responsible for β-lactamase production, was present in 93.9% of Neisseria spp. isolates, all of which showed resistance to penicillin.40 Genomic analysis of the 23 N. sicca isolates revealed resistance patterns, all of which harbored multiple macrolide resistance genes (including mtrC, mtrD, marA, marB, and lsaC), whereas specific isolates carried additional β-lactamase genes (TEM-1 in strains GCA_003044345 and GCA_019334765; TEM-50 in GCA_963456655) (Figure 4). Fortunately, most blaTEM-positive commensal Neisseria spp. are susceptible to cephalosporins.40 However, the commensal species, N. cinerea and N. elongata, demonstrated resistance to ceftriaxone.38
To the best of our knowledge, published reports indicates that N. sicca is generally susceptible to third-generation cephalosporins, β-lactamase inhibitors, penicillins, and quinolones. However, no CLSI criteria are currently available for this organism, and breakpoints for Neisseria meningitidis were therefore applied as a reference in susceptibility testing. In patients with AVR who develop BSIs concomitant with infective endocarditis, treatment poses additional challenges due to the potential formation of bacterial biofilms on prosthetic materials, which can reduce antibiotic efficacy and increase the risk of persistent infection.41 Therefore, combination therapy—including aminoglycosides or rifampin—may be considered to enhance antimicrobial activity and target biofilm-associated bacteria,42,43 with the final regimen tailored according to local resistance patterns and individual susceptibility results.
This case report had several limitations. First, the definitive diagnosis of endocarditis in our patient remains elusive, as we lacked TEE and other advanced imaging modalities such as cardiac CT or PET/CT, relying solely on TTE. Second, in the absence of CLSI susceptibility breakpoints for N. sicca, we used ATB HAEMO CLSI (12) strips, referring to the susceptibility breakpoints for Haemophilus influenzae. Third, although the virulence genes of N. sicca have been identified through whole-genome sequencing, their expression levels have not yet been verified using qPCR. Furthermore, we did not perform in vivo animal model experiments to validate virulence.
Conclusions
In summary, this case study provides the first genomic insight into the virulence and resistance characteristics of N. sicca implicated in BSIs in patients with AVR. These findings provide valuable information for future research on the pathogenicity and antibiotic resistance mechanisms of this microorganism in clinical contexts. Although N. sicca is generally susceptible to β-lactams, determining its sensitivity is highly advisable for guiding appropriate therapies. N. sicca commonly resides as a commensal bacterium on the mucosal surface of the human URT. However, its potential pathogenicity, particularly in BSIs arising from underlying heart valve disease, warrants further investigation.
Data Sharing Statement
Data supporting the findings of this study are openly available at https://trace.ncbi.nlm.nih.gov/Traces/index.html?view=run_browser&acc=SRR29061210&display=metadata reference number SRR29061210.
Ethics Approval and Consent to Participate
Whole genome sequencing, along with a case report, was approved by the Ethics Committee of Sanmen People’s Hospital in Taizhou, China.
Patient Consent for Publication
The patient provided written informed consent for the publication of case details and accompanying images.
Funding
This research received no external funding.
Disclosure
The authors declare that they have no competing interests in this work.
References
1. Donati C, Zolfo M, Albanese D, et al. Uncovering oral Neisseria tropism and persistence using metagenomic sequencing. Nat Microbiol. 2016;1(7):16070. doi:10.1038/nmicrobiol.2016.70
2. Merz AJ, So M. Interactions of Pathogenic neisseriae with Epithelial Cell Membranes. Annu Rev Cell Dev Biol. 2000;16(1):423–457. doi:10.1146/annurev.cellbio.16.1.423
3. Hung MC, Christodoulides M. The biology of Neisseria adhesins. Biology. 2013;2(3):1054–1109. doi:10.3390/biology2031054
4. Sommerstein R, Ramsay D, Dubuis O, Waser S, Aebersold F, Vogt M. Fatal Neisseria sicca endocarditis. Infection. 2013;41(3):747–749. doi:10.1007/s15010-012-0393-8
5. Jeurissen A, Stroy JP, Wielenga RP, Andriesse GI. Severe infective endocarditis due to Neisseria sicca: case report and review of literature. Acta Clin Belg. 2006;61(5):256–258. doi:10.1179/acb.2006.043
6. Gilrane T, Tracy JD, Greenlee RM, Schelpert III JW, Brandstetter RD. Neisseria sicca pneumonia. Report of two cases and review of the literature. Am J Med. 1985;78(6):1038–1040. doi:10.1016/0002-9343(85)90230-X
7. Gris P, Vincke G, Delmez JP, Dierckx JP. Neisseria sicca pneumonia and bronchiectasis. Eur Respir J. 1989;2(7):685–687. doi:10.1183/09031936.93.02070685
8. Moon T, Lin RY, Jahn AF. Fatal frontal sinusitis due to Neisseria sicca and Eubacterium lentum. J Otolaryngol. 1986;15(3):193–195.
9. Doern GV, Blacklow NR, Gantz NM, Aucoin P, Fischer RA, Parker DS. Neisseria sicca osteomyelitis. J Clin Microbiol. 1982;16(3):595–597. doi:10.1128/jcm.16.3.595-597.1982
10. Carter JE, Mizell KN, Evans TN. Neisseria sicca meningitis following intracranial hemorrhage and ventriculostomy tube placement. Clin Neurol Neurosurg. 2007;109(10):918–921. doi:10.1016/j.clineuro.2007.08.003
11. Kozlova A, Palazzolo L, Michael A. Neisseria sicca: a Rare Cause of Bacterial Conjunctivitis. Am J Case Rep. 2020;21:e923135. doi:10.12659/AJCR.923135
12. Neu AM, Case B, Lederman HM, Fivush BA. Neisseria sicca peritonitis in a patient maintained on chronic peritoneal dialysis. Pediatr Nephrol. 1994;8(5):601–602. doi:10.1007/BF00858142
13. Zhang M, Zhang X, Yin X, et al. Peritoneal dialysis-associated peritonitis caused by Neisseria.sicca: a case report and literature review. Indian J Med Microbiol. 2024;48:100566. doi:10.1016/j.ijmmb.2024.100566
14. Jung JJ, Vu DM, Clark B, Keller FG, Spearman P. Neisseria sicca/subflava bacteremia presenting as cutaneous nodules in an immunocompromised host. Pediatr Infect Dis J. 2009;28(7):661–663. doi:10.1097/INF.0b013e318196bd48
15. Morla N, Guibourdenche M, Riou JY. Neisseria spp. and AIDS. J Clin Microbiol. 1992;30(9):2290–2294. doi:10.1128/jcm.30.9.2290-2294.1992
16. Loonen AJ, Wolffs PF, Bruggeman CA, van den Brule AJ. Developments for improved diagnosis of bacterial bloodstream infections. Eur J Clin Microbiol Infect Dis. 2014;33(10):1687–1702. doi:10.1007/s10096-014-2153-4
17. Holland TL, Baddour LM, Bayer AS, Hoen B, Miro JM, Fowler Jr VG. Infective endocarditis. Nat Rev Dis Primers. 2016;2(1):16059. doi:10.1038/nrdp.2016.59
18. Heiddal S, Sverrisson JT, Yngvason FE, Cariglia N, Kristinsson KG. Native-valve endocarditis due to Neisseria sicca: case report and review. Clin Infect Dis. 1993;16(5):667–670. doi:10.1093/clind/16.5.667
19. Feder Jr HM, Garibaldi RA. The significance of nongonococcal, nonmeningococcal Neisseria isolates from blood cultures. Rev Infect Dis. 1984;6(2):181–188. doi:10.1093/clinids/6.2.181
20. Shaw FW. The Pathogenicity of Neisseria Sicca. Science. 1932;75(1949):488. doi:10.1126/science.75.1949.488.a
21. Kirlew C, Wilmot K, Salinas JL. Neisseria sicca Endocarditis Presenting as Multiple Embolic Brain Infarcts. Open Forum Infect Dis. 2015;2(3):ofv105. doi:10.1093/ofid/ofv105
22. McHugh J, Khawaja T, Baddour LM, et al. Bloodstream infection and risk of endocarditis following cardiac valve repair: a population-based study. Open Forum Infect Dis. 2020;7(Suppl 1):S401. doi:10.1093/ofid/ofaa439.893
23. Ostergaard L, Valeur N, Ihlemann N, et al. Incidence and factors associated with infective endocarditis in patients undergoing left-sided heart valve replacement. Eur Heart J. 2018;39(28):2668–2675. doi:10.1093/eurheartj/ehy153
24. Talha KM, McHugh JW, DeSimone DC, et al. Bloodstream infections in patients with transcatheter aortic valve replacement. Diagn Microbiol Infect Dis. 2021;101(3):115456. doi:10.1016/j.diagmicrobio.2021.115456
25. Brandao M, Goncalves-Teixeira P, Queiros PR, Ferreira ND, Oliveira M. Prosthetic Aortic Valve Endocarditis by Neisseria Elongata after Bentall Procedure: when Multimodality Imaging is Key to Diagnosis. Arq Bras Cardiol. 2021;116(5):1023–1026. doi:10.36660/abc.20200706
26. Picu C, Mille C, Popescu GA, Bret L, Prazuck T. Aortic prosthetic endocarditis with Neisseria elongata subspecies nitroreducens. Scand J Infect Dis. 2003;35(4):280–282. doi:10.1080/0036554021000027003
27. Ivanovic B, Trifunovic D, Matic S, Petrovic J, Sacic D, Tadic M. Prosthetic valve endocarditis – A trouble or a challenge? J Cardiol. 2019;73(2):126–133. doi:10.1016/j.jjcc.2018.08.007
28. Lo Presti S, Elajami TK, Zmaili M, Reyaldeen R, Xu B. Multimodality imaging in the diagnosis and management of prosthetic valve endocarditis: a contemporary narrative review. World J Cardiol. 2021;13(8):254–270. doi:10.4330/wjc.v13.i8.254
29. Iung B, Rouzet F, Brochet E, Duval X. Cardiac Imaging of Infective Endocarditis, Echo and Beyond. Curr Infect Dis Rep. 2017;19(2):8. doi:10.1007/s11908-017-0560-2
30. Cheng Q, Zhou X, Wang P, Liu R, Liu Q. Infective Endocarditis Caused by Neisseria Sicca Species 10 Years After Mechanical Aortic Valve Implantation. Infect Drug Resist. 2024;17:2785–2791. doi:10.2147/IDR.S467854
31. Locke M, Smith A, Epstein LM, Niknam N, Boparai R. Pacemaker lead-related endocarditis with Neisseria sicca. BMJ Case Rep. 2022;15(7):e249795. doi:10.1136/bcr-2022-249795
32. Lee EH, Shafer WM. The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids. Mol Microbiol. 1999;33(4):839–845. doi:10.1046/j.1365-2958.1999.01530.x
33. Merz AJ, So M, Sheetz MP. Pilus retraction powers bacterial twitching motility. Nature. 2000;407(6800):98–102. doi:10.1038/35024105
34. Arking D, Tong Y, Stein DC. Analysis of lipooligosaccharide biosynthesis in the Neisseriaceae. J Bacteriol. 2001;183(3):934–941. doi:10.1128/JB.183.3.934-941.2001
35. Seib KL, Wu HJ, Kidd SP, Apicella MA, Jennings MP, McEwan AG. Defenses against oxidative stress in Neisseria gonorrhoeae: a system tailored for a challenging environment. Microbiol Mol Biol Rev. 2006;70(2):344–361. doi:10.1128/MMBR.00044-05
36. Placzkiewicz J, Adamczyk-Poplawska M, Kozlowska E, Kwiatek A. Both Neisseria gonorrhoeae and Neisseria sicca Induce Cytokine Secretion by Infected Human Cells, but Only Neisseria gonorrhoeae Upregulates the Expression of Long Non-Coding RNAs. Pathogens. 2022;11(4):394. doi:10.3390/pathogens11040394
37. Dunn KL, Virji M, Moxon ER. Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili. Microb Pathog. 1995;18(2):81–96. doi:10.1016/S0882-4010(95)90085-3
38. Goytia M, Thompson ST, Jordan SVL, King KA. Antimicrobial Resistance Profiles of Human Commensal Neisseria Species. Antibiotics (Basel). 2021;10(5):538. doi:10.3390/antibiotics10050538
39. Chen M, Zhang C, Zhang X, Chen M. Meningococcal Quinolone Resistance Originated from Several Commensal Neisseria Species. Antimicrob Agents Chemother. 2020;64(2):e01494–19. doi:10.1128/AAC.01494-19
40. Sunil A, Kumar K, Sridharan KS. Presence of the blaTEM Gene in Commensal Neisseria spp.: a Possible Cause for the Acquired Drug Resistance Among Pathogenic Respiratory Bacteria. Cureus. 2023;15(11):e49389. doi:10.7759/cureus.49389
41. Cusumano JA, Kalogeropoulos AP, Le Provost M, et al. The emerging challenge of Enterococcus faecalis endocarditis after transcatheter aortic valve implantation: time for innovative treatment approaches. Clin Microbiol Rev. 2024;37(4):e0016823. doi:10.1128/cmr.00168-23
42. Jacqueline C, Caillon J. Impact of bacterial biofilm on the treatment of prosthetic joint infections. J Antimicrob Chemother. 2014;69(1):i37–40. doi:10.1093/jac/dku254
43. Khan F, Pham DTN, Kim YM. Alternative strategies for the application of aminoglycoside antibiotics against the biofilm-forming human pathogenic bacteria. Appl Microbiol Biotechnol. 2020;104(5):1955–1976. doi:10.1007/s00253-020-10360-1