Neisseria meningitidis is a Gram-negative diplococcus that rarely causes invasive diseases in Japan. We report a case of polyarticular meningococcal septic arthritis in an immunocompetent 62-year-old Japanese man. After 3 days of fever, he developed pain in the dorsum of the right hand and right shoulder. Computed tomography revealed effusions in the right wrist and acromioclavicular joint. Blood cultures grew N. meningitidis serogroup Y, sequence type 1655. A PCR assay detected the 16S rRNA gene of N. meningitidis in culture-negative wrist synovial fluid. Treatment with ceftriaxone followed by oral amoxicillin led to a complete recovery.

Neisseria mucosa is a Gram-negative diplococcus that usually colonizes the upper respiratory tract and is generally regarded as a commensal organism. It has, nevertheless, been implicated as an opportunistic pathogen in bacteremia, endocarditis, septic arthritis, meningitis, and peritoneal dialysis-associated peritonitis; urinary tract infection (UTI) remains exceptionally rare. We report a UTI caused by N. mucosa in a 24-day-old male neonate with posterior urethral valves (PUVs), who presented with frank pyuria for 10 days. Direct Gram staining of urine revealed Gram-negative diplococci with a coffee-bean morphology, and the organism was recovered in pure culture. Species identification was achieved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing by ETEST® showed susceptibility to ceftriaxone and resistance to benzylpenicillin and ciprofloxacin. Treatment with ceftriaxone was associated with a favorable clinical and biological outcome. This case illustrates the opportunistic potential of N. mucosa in neonates with structural urinary tract abnormalities and emphasizes the value of accurate microbiological identification when UTIs occur in an unusual clinical setting.

Human milk oligosaccharides (HMOs) are complex sugars in breast milk that protect babies by preventing harmful bacteria from colonizing the gut. Our team extended the study of HMOs beyond the neonatal gut and characterized their antimicrobial activity against group B Streptococcus (GBS), a diplococcus responsible for invasive perinatal infection. To date, the mechanism of action of this antimicrobial activity has remained obscure. To address this key gap, we employed untargeted proteomics, which revealed downregulation of PcsB, an essential murein hydrolase required for cell division. Following successful purification of the active domain of PcsB, we found that this protein domain restores GBS growth in the presence of HMOs, thereby validating PcsB as an HMO protein-interacting partner. In silico docking and molecular dynamics simulations predicted that two fucosylated HMOs, lacto-N-fucopentaose I (LNFPI) and lacto-N-fucopentaose III (LNFPIII), bind to PcsB. In silico predictions were validated using microscale thermophoresis assays, which reported dissociation constants of 5 ± 1 mM for LNFPI and 263 ± 72 μM for LNFPIII. Lastly, to test the hypothesis that HMOs may directly modulate the enzymatic activity of the CHAP domain, we employed a turbidimetric assay with commercial PG as the substrate. This assay provided further evidence that HMOs inhibit CHAP. Together, these data suggest that HMOs inhibit GBS growth by binding PcsB at its catalytic site, disturbing essential cell wall separation and division.

Gonorrhea is a sexually transmitted infection (STI) caused by Neisseria gonorrhoeae, a gram-negative diplococcus that primarily targets columnar and transitional epithelium, making the cervix, urethra, rectum, pharynx, and conjunctiva common sites of infection. The natural history of gonorrhea ranges from asymptomatic carriage to symptomatic disease, most commonly characterized by urethritis, cervicitis, or pelvic inflammatory disease (PID). Without treatment, the infection can spread to involve the uterus, fallopian tubes, and ovaries, or it can spread locally to adjacent structures, which can lead to serious sequelae, eg, infertility and ectopic pregnancy. In males, untreated infection can cause epididymitis, prostatitis, and urethral stricture. Hematogenous dissemination occurs in a minority of cases and can lead to arthritis, tenosynovitis, rash, endocarditis, and meningitis. Transmission is highly efficient through sexual contact, and untreated infection significantly increases the risk of partner transmission and coinfection with other STIs.

Neisseria meningitidis is a Gram-negative diplococcus commonly associated with meningitis or septicemia. However, it may rarely cause pulmonary abscesses, particularly in adults with risk factors such as smoking, chronic alcoholism, or underlying lung disease. The differential diagnosis should include other bacterial etiologies, and laboratory confirmation is essential. Recognition of atypical pulmonary presentations is crucial for appropriate management and mandatory reporting, given the potential for severe progression and the need for chemoprophylaxis among contacts. We report the case of a 60-year-old male, active smoker and chronic alcohol consumer, with a previous history of upper gastrointestinal bleeding requiring antrectomy. The patient presented with six months of anorexia and asthenia, melena of 15 days' duration, and worsening chronic cough. Laboratory findings revealed macrocytic hypochromic anemia, mild hyponatremia, and elevated inflammatory markers. Thoracic CT showed a thick-walled, cavitated mass in the middle lobe suggestive of malignancy. During hospitalization, the patient developed a fever. Bronchoscopy showed purulent, foul-smelling secretions at the middle lobe bronchial emergence. Microbiological analysis of bronchial secretions identified N. meningitidis. Directed therapy with intravenous ciprofloxacin (400 mg every eight hours) was initiated, and the patient was maintained under contact isolation, with subsequent clinical and laboratory improvement. Lung abscesses caused by N. meningitidis are a rare clinical entity, with few cases described in the literature; meningeal or septicemic involvement is far more common. This case underscores the need to considerN. meningitidis in the differential diagnosis of cavitary pulmonary lesions, particularly in patients with risk factors such as chronic smoking and alcoholism. The clinical presentation may mimic lung cancer or abscess, and identification requires microbiological confirmation from sputum or bronchoalveolar lavage samples. Prompt recognition is essential for adequate antibiotic therapy and public health measures. This case highlights the importance of considering N. meningitidis in the differential diagnosis of cavitary lung lesions, reinforcing the need for microbiological surveillance, multidisciplinary management, and targeted therapy.

Neisseria meningitidis (meningococcus) is a transitory colonizer of the human nasopharynx that occasionally, for largely unknown reasons, reaches the bloodstream, translocating across the nasopharyngeal mucosa, causing septicemia. The bloodstream spread of bacteria to the meninges can cause meningitis after crossing the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). Thus, the meningococcus must cross several epithelial and endothelial barriers to cause invasive meningococcal disease (IMD). While meningococcal interactions on the surface of epithelial and endothelial cells have been intensively investigated, leading to the identification of key determinants of virulence of this bacterium, relatively little is known about the crossing of the nasopharyngeal epithelial barrier (NEB), the BBB, and BCSFB by the meningococcus. Several mechanisms (transcellular and paracellular) have been proposed, including transcellular crossing and paracellular crossing that might be favored by an epicellular lifestyle of this bacterium. Little is also known about the prevalent (vacuolar or cytoplasmic) localization of N. meningitidis in infected epithelial and endothelial cells and the mechanisms adopted by this microorganism to survive and multiply in the intracellular environment. The purpose of this article is to collect and review what is actually known about the intracellular lifestyle of these microorganisms. The picture that emerges is that although it is traditionally considered an extracellular pathogen (despite its original name, Diplococcus intracellularis meningitidis [Weichseilbaum, 1887]), N. meningitidis engages in complex interactions with host cells in the intracellular microenvironment, involving signal transduction, membrane trafficking, cytoskeleton, metabolic cross-talk, and programmed cell death.

Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhea through sexual contact. This ancient STD remains a major public health concern due to reproductive health impacts, antimicrobial resistance (AMR), and lack of a vaccine. Cannabis sativa contains antibacterial cannabinoids, though its role in combating antibiotic resistance is underexplored. The 2Fe-2S iron-sulfur cluster protein is a potential antibiotic target, as these clusters are vital for bacterial proteins involved in electron transport, enzyme activity, and gene regulation. Disrupting them may impair bacterial survival and function. In this investigation, the 2Fe-2S iron sulfur cluster binding domain-containing protein (NGFG_RS03485), identified as a potential therapeutic target from the core proteome of 12 Neisseria gonorrhoeae strains, was selected for this study. Potential antimicrobial agents were explored through molecular docking studies involving 16 cannabinoid analogs-9 obtained from literature sources and 7 identified via fingerprint similarity searches. The study revealed that four cannabinoids form favorable bonds with active regions against our targeted protein; with a high binding affinity formed from the molecular docking; 1,3-Benzenediol, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-, (1R-trans). Dronabinol, Cannabinolic acid A (CBNA), Cannabigerolic acid (CBGA), and Ferruginene C are derivatives identified. Drug-likeness assessments were conducted to evaluate the pharmacokinetic and toxicity properties of the cannabinoids and compared against the antibiotics.

Moraxella catarrhalis is a Gram-negative diplococcus bacterium and a common respiratory pathogen, implicated in 15-20% of otitis media (OM) cases in children and chronic obstructive pulmonary disease (COPD) in adults. The rise of drug-resistant Moraxella catarrhalis has highlighted the urgent need for the potent vaccine strategies to reduce its clinical burden. Despite a mortality rate of 13%, there is no FDA-approved vaccine for this pathogen. The aim of this study was to computationally identify novel antigens and design a multi-epitope peptide-based vaccine candidate against M. catarrhalis using an immunoinformatics-driven subtractive proteomics and reverse vaccinology approaches. The core proteome of 12 M. catarrhalis genomes were analyzed, identifying 360 host non-homologous proteins. Subsequent screening revealed 30 metabolic pathway-dependent and 7 independent drug targets, along with 7 membrane and extracellular proteins as potential vaccine candidates. A prioritized protein target (WP_081569984.1) was selected for vaccine design. The predicted B-cell, MHC-I, and MHC-II epitopes were linked using adjuvants and linkers to construct four vaccine candidates (V1-V4). These constructs were assessed for physicochemical properties, allergenicity, antigenicity, secondary structures, and immune receptor interactions. As a result, V1 emerged as the most promising candidate. Molecular docking and molecular dynamics (MD) simulations evaluated the interactions of V1 with human toll-like receptors (TLR2 and TLR3). MD trajectories including RMSD, RMSF, Radius of gyration (Rg), SASA, binding free energy (MM-PBSA), PCA, free energy landscapes, and DCCM, showed a strong interaction of vaccine with the TLR recptors. Immune simulations predicted significant immune responses against the proposed vaccine. Additionally, the vaccine construct was in-silico tested in an E. coli plasmid vector (pET-28a(+) for its cloning potential. These findings highlight the potential of the proposed multi-epitope vaccine V1 as a safe and effective preventive strategy against M. catarrhalis-associated infections, and additionally laid the groundwork for future in vitro, in vivo, and clinical studies to validate its immunogenicity and protective efficacy.

Neisseria gonorrhoeae (N. gonorrhoeae) is a Gram-negative intracellular diplococcus that is commonly spread via sexual activity. The bacteremic spread of gonorrhoeae can lead to an uncommon complication called disseminated gonococcal infection (DGI). DGI has a range of clinical presentations, some of which are vague and nonspecific, including polyarthralgias, isolated septic arthritis, and systemic symptoms. Septic arthritis is a painful joint infection that can lead to inflammation, swelling, and limited mobility. We discuss a case of a male in his mid-70s with sudden bilateral wrist pain and swelling due to a DGI. The diagnosis was complicated by multiple unsuccessful arthrocentesis attempts ("dry taps") but was eventually confirmed by tissue culture, and the patient was treated with ceftriaxone. This report highlights a unique clinical presentation of DGI, the complex nature of its diagnosis, and the importance of thorough history taking.

Streptococcus pneumoniae, is a Gram-positive diplococcus, causes various community-acquired infections. Although pneumococcal vaccination has reduced the incidence of invasive pneumococcal disease, relative incidence of non-vaccine serotype-associated infections has increased. Herein, we report a case of pneumococcal infectious endocarditis and vertebral discitis diagnosed concurrently. A 73-year-old man presented with a 1-week history of fever and back pain (day 0). Laboratory tests revealed elevated inflammatory markers and magnetic resonance imaging confirmed vertebral osteomyelitis. Empirical intravenous cefazolin and vancomycin were initiated, considering appropriate coverage for common causative organisms of vertebral osteomyelitis. On day 1, blood cultures yielded S. pneumoniae- later identified as penicillin G susceptible serotype 23A belonging to sequence type 5242 -and antibiotics were switched to ceftriaxone and vancomycin. On the same day, the patient developed worsening oxygenation and a systolic murmur. Echocardiography revealed a mitral valve vegetation with severe regurgitation. Cefepime and vancomycin were initiated on day 2, followed by meropenem and vancomycin on day 4 for potential nosocomial pneumonia. On day 6, cefepime monotherapy was continued after methicillin-resistant Staphylococcus aureus was not detected in sputum culture. To address persistent respiratory failure, mitral valve replacement was performed on day 7. Cultures of tissue removed from the mitral valve were negative; 16S rRNA sequencing using the excised valve confirmed S. pneumoniae infection. Postoperatively, ceftriaxone was resumed, followed by oral levofloxacin, and a 42-day antimicrobial course was completed. The patient recovered without any recurrence. Continued surveillance of pneumococcal serotypes and antimicrobial resistance is warranted.

The genus Neisseria, a gram-negative diplococcus, includes commensal and pathogenic species that infect mucosal tissues, causing diseases such as gonorrhea and meningitis. The type VI secretion system (T6SS), a multifunctional molecular machine that facilitates the ability of gram-negative bacteria to deliver effectors for bacterial competition, virulence, and interaction with host cells, has been widely studied across various bacterial taxa. However, research on the T6SS in the genus Neisseria remains limited. In this study, we employed comparative genomics and pangenomics, among other bioinformatics approaches, to characterize the distribution of the T6SS and its related proteins, including effectors, immunity proteins and regulators, across different species within the genus. Through an analysis of 5,067 Neisseria genomes, we identified two complete T6SS loci. We found that more than half of the Neisseria species possess at least one complete T6SS locus. Further investigation revealed multiple T6SS-related loci. We also applied a statistics-based method for identifying T6SS-associated orthologous groups and revealed 64 new T6SS-associated proteins within the genus. Our research provides a comprehensive analysis of the T6SS in Neisseria, advancing the understanding of T6SS-related mechanisms.

For rod-shaped bacterial model organisms, the division plane is defined by the geometry of the cell. However, for Neisseria gonorrhoeae, a coccoid organism that most commonly exists as a diplococcus and that possesses genes coding for rod-based cell division systems, the relationship between cell geometry and division is unclear. Here, we characterized the organization of N. gonorrhoeae division using a combination of fluorescent probes, genetics, and time-lapse microscopy. We found that the planes of successive cell divisions are orthogonal and temporally overlapping, thereby maintaining diplococcal morphology. Division takes place perpendicular to a long axis in each coccus. In keeping with the ParABS and the MinCDE systems reading the more pronounced long axis of rod-shaped bacteria, in the coccoid N. gonorrhoeae, ParB segregates along this long axis and cells lacking minCDE suffer severe morphological consequences, including an inability to perform orthogonal division and aberrant assembly of the division plane at the cell poles. Taken together, this stresses the central role of even slight dimensional asymmetry as a general organizational principle in coccoid bacterial cell division.

Neisseria gonorrhoeae (N. gonorrhoeae)is a Gram-negative diplococcus responsible for sexually transmitted infections (STIs) worldwide. While gonorrhea primarily affects mucosal surfaces, disseminated gonococcal infection (DGI) can occur, presenting with polyarthritis, tenosynovitis, and dermatitis. However, atypical presentations can delay diagnosis and treatment. Men who have sex with men (MSM) are commonly affected by gonorrhea, necessitating vigilance for DGI in this population. A 24-year-old MSM with a history of previously treated gonorrhea presented with a petechial rash on the lower extremities and mild, painless foot swelling without systemic symptoms or joint involvement. The patient had engaged in multiple unprotected sexual encounters in the preceding month. Physical examination revealed a non-itchy, non-blanching rash, most prominent on the dorsum of the feet and sparing the soles. Laboratory findings showed leukocytosis and pyuria, while bacterial cultures remained negative. Nucleic acid amplification testing (NAAT) from urine was positive for N. gonorrhoeae, confirming the diagnosis. Given the absence of joint symptoms, purulent arthritis was considered unlikely, and leukocytoclastic vasculitis (LCV) was a differential diagnosis. However, the patient demonstrated significant improvement with ceftriaxone and doxycycline, supporting DGI as the primary diagnosis. He completed a seven-day course of ceftriaxone and oral doxycycline with full resolution of symptoms at follow-up. This case highlights an unusual presentation of DGI with isolated dermatologic manifestations and no tenosynovitis or arthritis. Methamphetamine use, previously linked to increased susceptibility to DGI, was noted in this patient. Negative blood and mucosal cultures emphasize the role of NAAT in diagnosing atypical DGI. Comparative case reviews demonstrate a wide spectrum of DGI presentations, reinforcing the need for early recognition. Clinicians should maintain a high index of suspicion for DGI, particularly in at-risk populations such as MSM, even in the absence of classic symptoms. Prompt diagnosis using NAAT and early antibiotic initiation are crucial for preventing complications. This case underscores the need for heightened awareness of atypical presentations to optimize patient outcomes.