Identification of novel putative immunogenic targets and construction of a multi-epitope vaccine against multidrug-resistant Corynebacterium jeikeium using reverse vaccinology approach.

The emergence of multidrug-resistant Corynebacterium jeikeium has limited treatment options and resulted in the inability to treat C. jeikeium infections, especially in immunocompromised patients. To our knowledge, no studies have been conducted to evaluate C. jeikeium antigens for vaccine development. Given the lack of effective treatments against C. jeikeium, this study aimed to identify potential immunogenic targets against C. jeikeium as a nosocomial pathogen using a reverse vaccinology approach. To achieve this goal, we performed several immuninformatics analyses, including antigenicity, allergenicity, PSI-BLAST to the human proteome, physiochemical properties, B-cell and T-cell epitopes, molecular docking, and immunosimulation. In addition, quartile scoring and prevalence assessment were used to select the most abundant immunogenic targets in different C. jeikeium strains. Finally, protein-protein interactions were performed and the multi-epitope vaccine was developed. Five putative immunogenic targets were presented as short-listed proteins in this study, including three enzymatic proteins (WP_011273969.1, WP_041626322.1, and WP_005292204.1), one protein with DUF3235 domain (WP_011273103.1), and one hypothetical protein (WP_005293648.1). Four linear B-cell epitopes of putative immunogenic targets, including WP_011273103.1 (LNSKPTPRNAAAKPKAK), WP_011273969.1 (GEGAQGSAAPADAQATANE), WP_005292204.1 (ASVSAAQKADGIAP), and WP_041626322.1 (YSKKVAEEMGVG) were selected and inserted into the mutant TbpB C-lobe protein. This platform can effectively present multiple epitopes to the immune system. However, experimental in vitro and in vivo analysis is required to confirm the safety, immunoreactivity, and efficacy of these putative immunogenic targets.

Corynebacterium jeikeium-induced infective endocarditis and perivalvular abscess diagnosed by 16S ribosomal RNA sequence analysis: A case report.

INTRODUCTION: Corynebacterium jeikeium normally presents on human skin, and it is often judged as contamination when it is cultured from blood. C. jeikeium can cause infective endocarditis, especially, that associated with cardiac surgery and prosthetic valvular endocarditis. CASE REPORT: A 66-year-old Japanese male patient was diagnosed with C. jeikeium-induced infective endocarditis (IE) and perivalvular abscess after a coronary artery bypass grafting and aortic valve replacement with bioprosthesis; pyogenic spondylodiscitis was also observed. Patch repair for aortic valve annulus and re-Bentall procedure with bioprosthesis was performed for IE and perivalvular abscess. The causative bacterium was confirmed as C. jeikeium on 16S ribosomal RNA sequencing of surgical sample and positive blood culture. The patient underwent six weeks of intravenous antibacterial treatment with vancomycin and an additional two weeks of oral treatment with linezolid, following which, his condition improved. Corynebacterium jeikeium can cause infective endocarditis and perivalvular abscess, which is a more severe condition than IE. CONCLUSION: 16S ribosomal RNA sequencing is useful in diagnosing bacterial species that can cause contamination, such as Corynebacterium spp.

Whole genome sequencing indicates Corynebacterium jeikeium comprises 4 separate genomospecies and identifies a dominant genomospecies among clinical isolates.

Corynebacterium jeikeium is an opportunistic pathogen which has been noted for significant genomic diversity. The population structure within this species remains poorly understood. Here, we explore the relationships among 15 clinical isolates of C. jeikeium (reference strains K411 and ATCC 43734, and 13 primary isolates collected over a period of 7 years) through genetic, genomic, and phenotypic studies. We report a high degree of divergence among strains based on 16S ribosomal RNA (rRNA) gene and rpoB gene sequence analysis, supporting the presence of genetically distinct subgroups. Whole genome sequencing indicates genomic-level dissimilarity among subgroups, which qualify as four separate and distinct Corynebacterium species based on an average nucleotide identity (ANIb) threshold of <95%. Functional distinctions in antibiotic susceptibilities and metabolic profiles characterize two of these genomospecies, allowing their differentiation from others through routine laboratory testing. The remaining genomospecies can be classified through a biphasic approach integrating phenotypic testing and rpoB gene sequencing. The genomospecies predominantly recovered from patient specimens does not include either of the existing C. jeikeium reference strains, implying that studies of this pathogen would benefit from examination of representatives from the primary disease-causing group. The clinically dominant genomospecies also has the smallest genome size and gene repertoire, suggesting the possibility of increased virulence relative to the other genomospecies. The ability to classify isolates to one of the four C. jeikeium genomospecies in a clinical context provides diagnostic information for tailoring antimicrobial therapy and may aid in identification of species-specific disease associations.

Infective Endocarditis Due to Corynebacterium jeikeium: Four Case Reports and Narrative Review of the Literature.

Corynebacterium jeikeium, a pleomorphic Gram-positive bacillus, is a common component of the cutaneous microbiota, usually considered as a contaminant, with little pathogenic potential. However, its role in various types of infections, such as bacteremia, sepsis, endocarditis (IE) and infection of prosthetic material is gradually being proven. Few cases of IE due to Corynebacterium jeikeium have been described in the literature. The aim of this article was to describe four cases of IE due to Corynebacterium jeikeium diagnosed in our hospital between May 2021 and April 2022, as well as to conduct a narrative review of the literature on this entity. After analysis, we highlight that 65.6% were men, 81.3% were valve or intravascular device carriers, and IE cases presented early, before one year after surgery. The most affected valve was the aortic valve (68.8%), followed by the mitral valve (21.1%). Valve replacement was performed in 65.6% of cases, and the most commonly used antibiotic was vancomycin (68.8%) at a dose of 15 mg/kg/12 h. With respect to prognosis, the overall mortality rate was 21.9%. The comparative results between our series and the literature review were similar except for a higher mortality rate (50%) and the use of dalbavancin in the treatment. We go on to review previously reported cases, along with four cases described in our hospital, of C. jeikeium endocarditis and will discuss various aspects of C. jeikeium infection, focusing on microbiology, pathophysiology, and treatment.

Exploration of the role of the penicillin binding protein 2c (Pbp2c) in inducible ß-lactam resistance in Corynebacteriaceae.

Six genes encoding putative high molecular weight penicillin-binding proteins (Pbp) are present in the genome of the ß-lactam-resistant strain Corynebacterium jeikeium K411. In this study, we show that pbp2c, one of these six genes, is present in resistant strains of Corynebacteriaceae but absent from sensitive strains. The molecular study of the pbp2c locus from C. jeikeium and its heterologous expression in Corynebacterium glutamicum allowed us to show that Pbp2c confers high levels of ß-lactam resistance to the host and is under the control of a ß-lactam-induced regulatory system encoded by two adjacent genes, jk0410 and jk0411. The detection of this inducible resistance may require up to 48 h of incubation, particularly in Corynebacterium amycolatum. Finally, the Pbp2c-expressing strains studied were resistant to all the ß-lactam antibiotics tested, including carbapenems, ceftaroline, and ceftobiprole.

Clinical Profile of Monomicrobial Corynebacterium Hip and Knee Periprosthetic Joint Infections.

Background: Corynebacterium periprosthetic joint infection (PJI) is a poorly described infectious syndrome. Prior studies included cases of polymicrobial infections. This series describes the clinical characteristics, management, and outcomes of monomicrobial Corynebacterium PJI. Methods: We queried the Mayo Clinic Total Joint Registry for cases of monomicrobial Corynebacterium knee and hip PJI in adults (age ≥18 years) between 2010 and 2019. Results: A total of 20 (1%) out of 2067 PJI cases met our inclusion criteria. Most were males (55%), and the median age was 64 years. Seventy percent had chronic symptoms (>4 weeks). PJI was delayed to late (>3 months postimplantation) in 90%. Three species were identified: C. striatum (70%), C. jeikeium (20%), and C. amycolatum (10%). All tested isolates were susceptible to vancomycin (100%) and linezolid (100%), and most had a minimum inhibitory concentration ≤0.06 mcg/mL to daptomycin (75%). Other agents were less reliable, with high resistance to oral agents commonly used for suppression. Nineteen patients were treated: 37% debridement and implant retention (DAIR), 47% 2-stage exchange, and 16% resection without reimplantation. Of these, failure occurred in 29%, 11%, and 0%, respectively. Conclusions: Corynebacterium PJIs pose a therapeutic challenge due to limited antimicrobial armamentarium and undefined optimal surgical intervention. Vancomycin and linezolid remain the most reliable agents for treatment. DAIR may be attempted for acute PJI, but verification of durable chronic suppression options will be critical for this approach.

Smells Like Teen Spirit-A Model to Generate Laundry-Associated Malodour In Vitro.

Although malodour formation on textiles and in washing machines has been reported to be a very relevant problem in domestic laundry, the processes leading to bad odours have not been studied intensively. In particular, the smell often described as "wet-and-dirty-dustcloth-like malodour" had not been reproduced previously. We developed a lab model based on a bacterial mixture of Micrococcus luteus, Staphylococcus hominis, and Corynebacterium jeikeium, which can produce this odour type and which might allow the detailed investigation of this problem and the development of counteractions. The model uses bacterial strains that have been isolated from malodourous textiles. We could also show that the three volatile compounds dimethyl disulfide, dimethyl trisulfide, and indole contribute considerably to the "wet-fabric-like" malodour. These substances were not only found to be formed in the malodour model but have already been identified in the literature as relevant malodourous substances.

Corynebacterium jeikeium as an Unusual Cause of Keratitis: A Case Report From a Tertiary Care Hospital in Chhattisgarh, India.

Bacterial keratitis is a serious, potentially sight-threatening complication in neglected cases of corneal trauma. Few bacteria and fungi are implicated in the pathogenesis of bacterial keratitis after trauma; however, keratitis by an opportunistic organism is rare. We report here a case of keratitis caused by Corynebacterium jeikeium (C. jeikeium) after accidental trauma with rice grains. The patient presented to us with chronic keratitis, which responded to 5% fortified vancomycin eye drops after microbiological investigation and drug sensitivity.

Internal-Fixation Hardware Infection With Corynebacterium jeikeium.

Corynebacterium is a rare cause of prosthetic joint infections (PJIs) and infection after fracture fixation (IAFF). We present a case of a patient who developed Corynebacterium jeikeium-associated IAFF three weeks after his fracture fixation. Due to its slow-growing nature, surgical cultures remained negative after 72 hours and grew only on day 5. We highlight that physicians should have Corynebacterium-associated infection in their differential in such cases, especially when the cultures remain negative after 72 hours. We also review the literature of PJI and implant-associated infection with C. jeikeium and discuss the antibiotic resistance patterns and some microbiological considerations associated with C. jeikeium.

LVAD Vasculitis Case Series: Suggestion of a New Fatal LVAD-Related Phenomenon.

Left ventricular assist devices (LVADs) are surgically implanted mechanical devices indicated for patients with advanced heart failure and are known to come with several complications. Here we present a case series, and review 1 documented report, of LVAD vasculitis, a presumed new LVAD immune/humoral related phenomenon. (Level of Difficulty: Advanced.).

Corynebacterium jeikeium native valve infective endocarditis case report: a confirmed microbiological and pathological diagnosis from heart valvular tissue.

BACKGROUND: The Modified Duke criteria is an important structured schematic for the diagnosis of infective endocarditis (IE). Corynebacterium jeikeium is a rare cause of IE that is often resistant to standard IE anti-microbials. We present a case of C. jeikeium IE, fulfilling the Modified Duke pathological criteria. CASE SUMMARY: A 50-year-old male presented with left leg peripheral vascular disease with septic changes requiring amputation. Routine echocardiography post-amputation demonstrated severe aortic valve regurgitation with vegetations that required valve replacement. Two initial blood cultures from a single venepuncture showed Streptococcus mitis which was treated with penicillin G prior to surgery. Subsequent aortic valve tissue cultured C. jeikeium with suggestive IE histological valvular changes and was successfully treated on a prolonged course of vancomycin. DISCUSSION: This is the first C. jeikeium IE case diagnosed on heart valvular tissue culture and highlights the importance for the fulfilment of the Modified Duke criteria in diagnosing left-sided IE. Mixed infection IE is rare, and this case possibly represents an unmasking of resistant C. jeikeium IE following initial treatment of penicillin G.

Corynebacterium jeikeium Dormant Cell Formation and Photodynamic Inactivation.

Pathogenic non-spore forming bacteria enter a dormant state under stressful conditions, which likely allows them to acquire resistance to various antibiotics. This work revealed the efficient formation of dormant "non-culturable" (NC) Corynebacterium jeikeium cells in stationary phase upon gradual acidification of the growth medium. Such cells were unable to form colonies and existed in a prolonged stationary phase. At an early stage of dormancy (approximately 14 days post-inoculation), dormant cells are able for resuscitation in liquid medium. However, those stored for long time in dormant state needed addition of supernatant taking from active C. jeikeium cultures for successful resuscitation. NC cells possessed low RNA synthesis and significant tolerance to antibiotics (rifampicin and vancomycin). They also accumulated free porphyrins, and 5-aminolevulinic acid addition enhanced free porphyrin accumulation which makes them potentially sensitive to photodynamic inactivation (PDI). PDI of dormant bacteria was accomplished by exposing cells to a 565 nm wavelength of light using a SOLIS-4C light-emitting diode for 60 min. This revealed that increased porphyrin concentrations were correlated with elevated PDI sensitivity. Results shown here demonstrate the potential utility of employing PDI to minimize levels of dormant, persistent corynebacteria and the C. jeikeium dormancy model developed here may be useful for finding new drugs and techniques for combatting persistent corynebacteria.

Incidental detection of Corynebacterium jeikeium endocarditis via regular blood examination in an afebrile hemodialysis patient.

Herein, we describe a rare case of Corynebacterium jeikeium endocarditis that silently progressed in a 65-year-old man undergoing hemodialysis. Because routine monthly blood examination revealed high C-reactive protein levels, blood cultures were collected, although he had no symptom and was afebrile. After 2 days, a Gram-positive rod was detected in one set of the blood culture. Furthermore, transthoracic echocardiography revealed new aortic regurgitation (AR) and vegetations, and, therefore, infective endocarditis was suspected. Transesophageal echocardiography showed vegetations with a maximum diameter of 8 mm on his aortic valve, with some valve destruction. C. jeikeium was identified in three sets of blood cultures. Administration of daptomycin was started because he had vancomycin allergy. Judging from the high risk of embolization due to vegetations, emergency aortic valve replacement was performed on the second day. C. jeikeium was detected in a resected cardiac valve specimen and blood. This case emphasizes that physicians should always consider the possibility of infective endocarditis even in hemodialysis patients without any symptoms.

Disseminated Corynebacterium jeikeium Infection in Cancer Patients.

Corynebacterium jeikeium is a multidrug-resistant gram-positive bacterium of the human skin flora and one of the most clinically important nondiphtherial corynebacteria in the acute care setting. C. jeikeium can cause different forms of infections, especially in immunocompromised patients with underlying risk factors and comorbidities. C. jeikeium was initially described in 1976 as a highly resistant coryneform bacteria causing severe sepsis in patients with hematologic malignancies and profound neutropenia. C. jeikeium infection has also been reported in the setting of endocarditis, septicemia, meningitis, pneumonia, and soft tissue infections. Management of disseminated C. jeikeium infection in immunocompromised cancer patients can be challenging due to its high virulence and rapid skin colonization. We present two cases of disseminated C. jeikeium infection in patients with acute myelogenous leukemia (AML) and underlying comorbidities. Both patients presented with neutropenic fever resistant to initial standard empiric antibiotic therapy.

Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities.

Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4-8 and 0.125-0.25 µM, respectively, along with a non-toxic profile after a short- and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor.

A case of recurrent Corynebacterium jeikeium endocarditis: Unanswered questions for the treatment of chronic endovascular infections.

A 53-year-old woman with end-stage renal impairment on hemodialysis was evaluated for recurrent episodes of Corynebacterium jeikeium bacteremia and endocarditis. Her recurrences occurred despite surgical debridement and extended courses of culture-directed antimicrobial therapy. The clinical course was complicated by the requirement of various endovascular prostheses for vascular access. To our knowledge this degree of relapse with guideline medical and surgical therapy is rare and challenges current practice and understanding of this group of infection.