Infective endocarditis caused by Gemella species is increasingly recognized as an emerging clinical entity. Gemella species are fastidious gram-positive cocci that are typically commensal organisms but can become opportunistic pathogens. This systematic review aimed to provide a comprehensive overview of endocarditis due to Gemella species by synthesizing existing evidence. A total of 52 case reports were identified through a rigorous search and selection process. The most prevalent causative species were G. morbillorum (46.3%) and G. haemolysans (25.9%), with a striking male predominance (79.6%). The clinical presentation was largely nonspecific, mirroring typical infective endocarditis. However, the indolent nature of the illness and fastidious growth requirements of Gemella species often led to diagnostic delays. Echocardiography, particularly transesophageal echocardiography, played a crucial role in the diagnosis, enabling the detection of valvular vegetation and the assessment of complications. Management posed significant challenges, including the need for broad-spectrum empirical antibiotic therapy and increasing antimicrobial resistance among Gemella isolates. Surgical intervention was frequently required for severe valvular dysfunction, persistent infection, or embolic complications. Despite advances in diagnosis and treatment, endocarditis due to Gemella species remains associated with significant morbidity and mortality, underscoring the importance of early recognition and multidisciplinary management. This review highlights the emerging clinical significance of Gemella species as causative agents of infective endocarditis and identifies areas for further research.

This is the case of a 31-year-old man with no significant past medical history who presented to the emergency department experiencing persistent fevers, chills, and malaise for the past 2-3 weeks. During this period, he had multiple urgent care visits for possible left-sided otitis media which was treated with short a course of Augmentin. While on antibiotics his symptoms would improve, but they would reappear once he had finished treatment. The patient also had significant dental carries with a chronic right molar infection. At the emergency department, blood cultures grew two out of two Gemella morbillorum. Transthoracic echocardiography showed a 1 cm x 0.5 cm mobile density on the left coronary cusp of the aortic valve with moderate-severe aortic insufficiency. The patient was started on empiric IV vancomycin. Further workup revealed that the source of infection was dental carries. While proceeding with a transesophageal echocardiogram, the patient went into flash pulmonary edema requiring ICU admission. Imaging revealed an elongated 1.7 cm x 0.6 cm vegetation attached to the base of the left coronary cusp on the left ventricular outflow tract side with severe aortic regurgitation and a small 0.8 cm x 0.8 cm vegetation on the atrial side of the anterior mitral leaflet at A2 associated with mitral leaflet perforation with severe mitral regurgitation. Oral surgery removed the infected teeth. Cardiothoracic surgery performed open heart valve replacement which revealed a completely destroyed aortic valve, droplet vegetation, and destruction of the mitral valve leading to mechanical valve replacement. The patient received a two-week course of gentamycin while in the ICU with meropenem. Once sensitivities were back, he was switched to IV penicillin therapy for a total of six weeks.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumours with increasing incidence, and oral leukoplakia (OLK) has a strong tendency to undergo malignant transformation. The oral microbiota may influence oral cancer progression, but the salivary bacterial composition and functional changes in OSCC and OLK have not been comprehensively elucidated. Therefore, we compared salivary bacteria in OLK and OSCC patients with healthy controls (HC).
Metagenomic sequencing was used to compare the bacterial composition and functional changes of 18 OSCC patients, 21 OLK patients and 21 HC. Spearman correlation was used to identify possible associations between functions and bacteria.
Gemella was the most differentially enriched genus in OSCC. At the species level, Streptococcus sp. NPS 308, Streptococcus agalactiae, Gemella haemolysans and Gemella morbillorum were slightly increased in OLK and OSCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that OSCC was mainly associated with metabolism functions, including lipid metabolism, carbohydrate metabolism and glycan biosynthesis and metabolism. The synthesis and degradation of ketone bodies, cysteine and methionine metabolism and glycerolipid metabolism differed significantly among the three groups, and were highest in OSCC and lowest in HC. And G. haemolysans was significantly associated with these selected metabolic pathways.
Metagenomic analysis revealed significant differences in the salivary microbiota among OSCC, OLK and HC. Thus, salivary microbiota composition and functional changes may be associated with OSCC progression. Metabolism of nonessential amino acids such as cysteine and methionine in bacteria may play an important role in oral oncogenesis, and more studies of the mechanism between metabolisms of bacteria and oral oncogenesis are needed in the future.

Valvular heart disease (VHD) occurs when there is a functional impairment in the valvular apparatus that either obstructs or regurgitates the backflow of blood. When a microorganism resides in those valves, it injures the leaflets and causes complications such as thromboembolic events. Infective endocarditis (IE), usually caused by the Staphylococci and Streptococcus group, is a disease that occurs on the heart valves. Antibiotic resistance is common; thus, culture and sensitivity testing should be done for a more targeted treatment approach. We herein present a rare case of Gemella morbillorum (G. morbillorum) vegetations found in a patient\'s heart that initially presented with cerebrovascular disease symptoms and underwent heart surgery in the end.

The family Staphylococcacae and genus Gemella contain several organisms of clinical or biotechnological importance. We report here comprehensive phylogenomic and comparative analyses on 112 available genomes from species in these taxa to clarify their evolutionary relationships and classification. In a phylogenomic tree based on 678 core proteins, Gemella species were separated from Staphylococcacae by a long branch indicating that they constitute a distinct family (Gemellaceae fam. nov.). In this tree, Staphylococcacae species formed two main clades, one encompassing the genera Aliicoccus, Jeotgalicoccus, Nosocomiicoccus and Salinicoccus (Family \"Salinicoccaceae\"), while the other clade consisted of the genera Macrococcus, Mammaliicoccus and Staphylococcus (Family Staphylococcaceae emend.). In this tree, species from the genera Gemella, Jeotgalicoccus, Macrococcus and Salinicoccus each formed two distinct clades. Two species clades for these genera are also observed in 16S rRNA gene trees and supported by average amino acid identity analysis. We also report here detailed analyses on protein sequences from Staphylococcaceae and Gemella genomes to identify conserved signature indels (CSIs) which are specific for different genus and family-level clades. These analyses have identified 120 novel CSIs robustly demarcating different proposed families and genera. The identified CSIs provide independent evidence that the genera Gemella, Jeotgalicoccus, Macrococcus and Salinicoccus consist of two distinct clades, which can be reliably distinguished based on multiple exclusively shared CSIs. We are proposing transfers of the species from the novel clades of the above four genera into the genera Gemelliphila gen. nov., Phocicoccus gen. nov., Macrococcoides gen. nov. and Lacicoccus gen. nov., respectively. The identified CSIs also provide strong evidence for division of Staphylococcaceae into an emended family Staphylococcaceae and two new families, Abyssicoccaceae fam. nov. and Salinicoccaceae fam. nov. All of these families can be reliably demarcated based on several exclusively shared CSIs.

Gemella species are core members of the human oral microbiome in healthy subjects and are regarded as commensals, although they can cause opportunistic infections. Our objective was to evaluate the site-specialization of Gemella species among various habitats within the mouth by combining pangenomics and metagenomics. With pangenomics, we identified genome relationships and categorized genes as core and accessory to each species. With metagenomics, we identified the primary oral habitat of individual genomes. Our results establish that the genomes of three species, G. haemolysans, G. sanguinis and G. morbillorum, are abundant and prevalent in human mouths at different oral sites: G. haemolysans on buccal mucosa and keratinized gingiva; G. sanguinis on tongue dorsum, throat, and tonsils; and G. morbillorum in dental plaque. The gene-level basis of site-specificity was investigated by identifying genes that were core to Gemella genomes at a specific oral site but absent from other Gemella genomes. The riboflavin biosynthesis pathway was present in G. haemolysans genomes associated with buccal mucosa but absent from the rest of the genomes. Overall, metapangenomics show that Gemella species have clear ecological preferences in the oral cavity of healthy humans and provides an approach to identifying gene-level drivers of site specificity.

A 53-year-old male with active IV heroin use presented with left upper extremity pain, erythema, swelling, and purulent foul-smelling drainage. Rapid diagnosis of necrotizing soft tissue infection (NSTI) was made based on clinical and radiologic findings. He was taken to the operating room for wound washouts and surgical debridements. The early microbiologic diagnosis was made based on intraoperative cultures. Successful treatment of NSTI in the setting of rare pathogens was achieved. The wound was ultimately treated with wound vac therapy, followed by primary delayed closure of the upper extremity and skin grafting of the forearm. We present a case of NSTI secondary to Streptococcus constellatus, Actinomyces odontolyticus, and Gemella morbillorum in an intravenous (IV) drug user, successfully treated with early surgical intervention.

Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.

Gemella bergeri, a member of the genus Gemella, is a facultatively anaerobic, Gram-positive cocci. G. bergeri is a component of normal oral flora; however, it can become pathogenic and cause infections in patients with poor oral hygiene. A 78-year-old man was admitted to a hospital with a complaint of increasing posterior neck pain and lower back pain for 2 weeks. MRI was suggestive of infectious spondylitis at the C3-C4 level with prevertebral abscess formation, anterior epidural abscess formation. We identified Gemella bergeri in closed pus obtained during the surgery. Herein, we describe the first case of infective spondylitis caused by G. bergeri.

The human oral microbiome is associated with chronic diseases including cancer. However, our understanding of its relationship with diet is limited. We assessed the associations between carbohydrate and glycemic index (GI) with oral microbiome composition in 834 non-diabetic subjects from the NCI-PLCO and ACS-CPSII cohorts. The oral microbiome was characterized using 16Sv3-4 rRNA-sequencing from oral mouthwash samples. Daily carbohydrate and GI were assessed from food frequency questionnaires. We used linear regression, permutational MANOVA, and negative binomial Generalized Linear Models (GLM) to test associations of diet with α- and β-diversity and taxon abundance (adjusting for age, sex, cohort, BMI, smoking, caloric intake, and alcohol). A q-value (FDR-adjusted P-value) of <0.05 was considered significant. Oral bacterial α-diversity trended higher in participants in the highest quintiles of carbohydrate intake, with marginally increased richness and Shannon diversity (p-trend=0.06 and 0.07). Greater carbohydrate intake was associated with greater abundance of class Fusobacteriia (q=0.02) and genus Leptotrichia (q=0.01) and with lesser abundance of an Actinomyces OTU (q=4.7E-04). Higher GI was significantly related to greater abundance of genus Gemella (q=0.001). This large, nationwide study provides evidence that diets high in carbohydrates and GI may influence the oral microbiome.