Listeriosis Research Articles

Listeria in Pregnancy—The Forgotten Culprit

Listeria monocytogenes is a Gram-positive bacterium that causes listeriosis, a severe foodborne illness that is particularly dangerous during pregnancy. It thrives in diverse environments, including refrigerated conditions and food production facilities, due to its adaptability to varying temperatures, pH levels, and salt concentrations. Its virulence stems from the ability to invade host cells, particularly macrophages and epithelial cells, and avoid, or at least postpone, immune detection by utilizing virulence factors such as internalins, listeriolysin O, and actin assembly-inducing protein. This intracellular motility and biofilm formation make LM a persistent pathogen in food safety and public health. Pregnant women are at a much higher risk of listeriosis, which can result in serious fetal complications such as miscarriage, stillbirth, and preterm labor due to LM’s affinity for placental tissues. The vertical transmission of LM from mother to fetus can lead to neonatal listeriosis, which can result in sepsis and meningitis, with high mortality rates if not promptly treated. Early diagnosis and treatment with antibiotics, such as ampicillin or gentamicin, are crucial for maternal and neonatal outcomes.

Lysteria Monocytogenes Infection during Monochorionic Twin Pregnancy: Case Report and Review of the Literature.

Listeriosis is a rare but severe foodborne disease caused by Listeria Monocytogenes (LM), a small facultative intracellular bacillus. When occurring in pregnant women, it can be vertically transmitted to the fetus and the newborn. Infected women usually display aspecific and mild symptoms, and rarely develop the severe forms of the disease (such as neurolisteriosis). On the contrary, fetal and neonatal listeriosis can lead to complications such as fetal loss, preterm birth, neonatal sepsis, and respiratory distress syndrome (RDS). Prompt diagnosis is one of the main challenges because of the aspecific presentation of the disease; therapy relies on antibiotics that reach high intracellular concentration and can penetrate and pass the placenta reaching the fetus. Herein we report an infrequent case of LM infection involving a woman with monochorionic diamniotic twin pregnancy, followed by a comprehensive review of the available literature on listeriosis in pregnancy.

Ulk1 regulates T Cell Development and Response to Listeria monocytogenes Stimulation.

T cells are crucial for the normal functioning of the immune system. The development and response of these cells to foreign antigens involve many complex stages and interactions between various types of cells. However, many details of these processes are still unclear. Our research revealed a key role for a protein called ULK1, a serine/threonine protein kinase, in regulating T-cell development and function. During T-cell maturation, the absence of Ulk1 (as in Ulk1-/- mice) leads to an increase in a cell type called DN3 in the thymus. We also found a reduction in the number of T cells in peripheral immune organs, such as the spleen, in Ulk1-/- mice. In response to Listeria infection, Ulk1-/- mice have a weaker ability to clear this bacterium, and their T cells also have defects in producing cytokines. However, the absence of Ulk1 did not affect the activation or apoptosis of naïve CD4+ T cells in vitro. In a bone marrow chimeric mouse model, T cells from Ulk1-/- mice did not differ developmentally from those from control mice. Furthermore, RNA-seq revealed that Ulk1 deficiency affects the metabolic function of splenocytes and T-cell function in mice, potentially through the canonical Wnt signaling cascade and the ERK1/ERK2 signaling cascades. Overall, these results suggest that Ulk1 is essential for T-cell maturation in the thymus, the balance of peripheral T cells, and the functional response of T cells to antigens.

Suppressive effect of the anesthetic propofol on the T cell function and T cell-dependent immune responses

General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.

Immunopeptidomics Mapping of Listeria monocytogenes T Cell Epitopes in Mice

Listeria monocytogenes is a foodborne intracellular bacterial model pathogen. Protective immunity against Listeria depends on an effective CD8+ T cell response, but very few T cell epitopes are known in mice as a common animal infection model for listeriosis. To identify epitopes, we screened for Listeria immunopeptides presented in the spleen of infected mice by mass spectrometry-based immunopeptidomics. We mapped more than 6000mouse self-peptides presented on MHC class I molecules, including 12 high confident Listeria peptides from 12 different bacterial proteins. Bacterial immunopeptides with confirmed fragmentation spectra were further tested for their potential to activate CD8+ T cells, revealing VTYNYINI from the putative cell wall surface anchor family protein LMON_0576 as a novel bona fide peptide epitope. The epitope showed high biological potency in a prime boost model and can be used as a research tool to probe CD8+ T cell responses in the mouse models of Listeria infection. Together, our results demonstrate the power of immunopeptidomics for bacterial antigen identification.

A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death.Case PresentationWe report a case of a 30-year-old female presenting with “repeated high fever with symptoms of headache for 14 days”. On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient’s diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found.ConclusionThis case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.

Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes Infection: A 12-Year Hospital-Based Study in Xi'an, China.

Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Increased incidence and mortality from Listeria monocytogenes infection in Spain

ObjectivesListeria monocytogenes (LM) is a health threat worldwide given its high mortality and the growing of high-risk susceptible populations. MethodsAll hospitalizations with a diagnosis of LM in the National Registry of Hospital Discharges were examined in Spain from 2000 to 2021. ResultsA total of 8152 hospital admissions with LM were identified. The mean age was 59.5 years and 48% were immunosuppressed (IS).The rate of LM hospitalizations increased from 5 per 1 million population in 2000 to 8.9 in 2021 (p < 0.001). A foodborne outbreak in Andalusia determined a sharp increase in admissions with LM during 2019. The COVID-19 pandemic and lockdowns were associated with a decrease in LM admissions.The overall in-hospital mortality was 16.7%. The number of deaths in patients hospitalized with LM rose from 7.8 per 100,000 deceased in 2000 to 18 in 2021 (p < 0.001). After adjustment, age >65 years (odds ratio [OR] = 2.16), sepsis (OR = 2.60), meningoencephalitis (OR = 1.72), endocarditis (OR = 2.0), neonatal listeriosis (OR = 2.10) and IS (OR = 2.09) were associated with mortality. ConclusionsThe number of patients hospitalized with LM in Spain has increased significantly from 2000 to 2021. The increase in the rate of admissions and deaths was largely driven by the growing proportion of elderly and IS patients.

Contamination of Food Products by Listeria monocytogenes in Iran during 2010-2023

Introduction: Mortality rate of Listeria infection is high and has been reported to be up to 30%. In this regard, the present study aimed to provide more information about food sources contaminated with the Listeria monocytogenes and offer suitable strategies to control this pathogen in supply centers, slaughterhouses, and processing centers. Method: Results of investigations on the prevalence of L. monocytogenes in food (seafood and aquatic products, red meat, poultry, and dairy products) during 2010-2023 were reviewed. In total, 61 acceptable studies were involved in the present research. After the selection of papers, their key results were extracted, including the prevalence of Listeria monocytogenes, cultivation method, sample type, and sampling location. Results: Listeria monocytogenes is prevalent in all types of seafood products, red meat, poultry, dairy products, and vegetables, as well as ready-to-eat and ready-to-cook foods. Consuming raw and undercooked foods contaminated with animal and human feces and direct contact with feces can cause Listeria infection in humans. L. monocytogenes is sensitive to amoxicillin, ampicillin, penicillin, and gentamicin antibiotics; therefore, these antibiotics can be used for listeriosis treatment. Conclusion: In previous studies, the importance of traditional meat and dairy supply centers in L. monocytogenes transmission has been addressed to a lesser extent. It can be concluded that appropriate standards should be developed and applied to control this food pathogen by regulatory systems. In addition, regular and periodic monitoring of food products and providing necessary training to people about how to prevent food poisoning can play an effective role in reducing listeriosis.

Clinical Outcome and Factors with Dietary Behaviors in Pregnant Women with Listeria monocytogenes: A Hospital-Based Case-Control Study in Shanghai.

Listeriosis is a globally rare foodborne disease that causes fetal-placental infection, leading to adverse pregnancy outcome, while limited research among pregnant women is available in China. This study was therefore aimed at analyzing the incidence, clinical manifestations, and clinical outcome of listeriosis among pregnant women and its associated dietary behavior risk factors in prevention. A hospital-based case-control study had been conducted from January 2017 to December 2021. Clinical data, laboratory information, and questionnaires including dietary behaviors and personal hygiene were collected within 2 days after case diagnosis. There were 48 pregnant women, including 12 cases and 36 controls, with an average age of 31.19 ± 3.75 years. The incidence of admission-based listeriosis among pregnant women was 1.6058 per 10,000. The 12 strains were divided into 3 serotypes: 1/2a(83.33%), 1/2b(8.33%), and 4b(8.33%). Among the cases, 5 cases (41.67%) resulted in abortion, 3 cases (25%) induced preterm labor, and 4 cases (33.33%) had full-term deliveries after treatment. There were 7 live births in the case group, among which 6 were admitted to the neonatal intensive care unit (NICU), while 1 case had a healthy fetal outcome. All patients in the control group gave birth to live fetuses. Epidemiological investigation revealed that pregnant women dining at restaurants three or more times per week might increase the risk of having Listeria infection. There were no significant differences in dietary consumed behaviors, hand hygiene, and refrigerator usage behaviors between case and control groups. The study suggested that dining at restaurants might be associated with Listeria infection among pregnant women. Therefore, it is essential to enhance education on listeriosis serious consequences and promote healthy dietary and hygiene habits among pregnant women.

The Transcription Factor Zfp335 Promotes Differentiation and Survival of Effector Th1 Cells by Directly Regulating Lmna Expression.

Ag-specific effector CD4+ T cells play a crucial role in defending against exogenous pathogens. However, the mechanisms governing the differentiation and function of IFN-γ-producing effector CD4+ Th1 cells in immune responses remain largely unknown. In this study, we elucidated the pivotal role of zinc finger protein 335 (Zfp335) in regulating effector Th1 cell differentiation and survival during acute bacterial infection. Mice with Zfp335 knockout in OT-II cells exhibited impaired Ag-specific CD4+ T cell expansion accompanied by a significant reduction in resistance to Listeria infection. Furthermore, Zfp335 deficiency restricted the effector CD4+ Th1 cell population and compromised their survival upon Listeria challenge. The expression of T-bet and IFN-γ was accordingly decreased in Zfp335-deficient Th1 cells. Mechanistically, Zfp335 directly bound to the promoter region of the Lmna gene and regulated its expression. Overexpression of Lmna was able to rescue the survival and function of Zfp335-deficient effector Th1 cells. Therefore, our study provides novel insights into the mechanisms governing effector Th1 cell differentiation and survival during acute infection.

Prevalence, Antimicrobial Resistance, and Characterization of Listeria Spp. Isolated from Various Sources in Ethiopia: A Comprehensive Review.

Listeriosis is an important foodborne zoonotic disease affecting humans and animals in Ethiopia. This review aims to synthesize the epidemiology, prevalence, distribution, and antimicrobial resistance of Listeria species in the country. The literature reveals a widespread occurrence of Listeria infection in humans, animals, and food products, with an average prevalence of 21.6% for Listeria species and 6.9% for L. monocytogenes. Three sequence types (STs) of L. monocytogenes (2, 145, and 18) and twelve STs of L. innocua (1489, 1619, 603, 537, 1010, 3186, 492, 3007, 1087, 474, 1008, and 637) were reported from milk and dairy products. Contamination rates ranged from 4.1% to 42.9% across livestock, dairy, slaughterhouses, and processing facilities, indicating faults in production practices. Sporadic human listeriosis outbreaks have occurred since 1967, causing meningitis, perinatal infections, and deaths, with recent studies showing L. monocytogenes isolation in up to 10.4% of febrile patients, confirming foodborne transmission. Non-pathogenic Listeria species were also common on farms and in facilities. Ovine listeriosis poses a threat to Ethiopia's sheep and goat industries, with over 40% seroprevalence in some herds. Comprehensive control measures across the food chain are needed to curb contamination and protect public health. Isolates from various foods show antibiotic resistance to first-line agents but susceptibility to others like gentamicin and cephalosporins. In conclusion, this review synthesizes evidence on Listeria distribution in Ethiopia's food system and disease burden, highlighting the need for improved food safety policies and awareness.

Potential PD-1 inhibitor immune dysregulation as a risk factor for Listeria monocytogenes bacteremia and meningitis

As immune checkpoint inhibitor (ICI) therapy becomes increasingly popular for the treatment of cancer, there is a growing body of literature on opportunistic infections associated with ICI therapy. Pembrolizumab binds specifically to the PD-1 receptor on T cells, preventing PD-1’s interaction with PD-L1 and PD-L2. This blockade interrupts the inhibitory signal and restores a T cell’s ability to recognize and attack tumor cells. We present a case of invasive Listeria infection associated with ICI therapy. The case also suggests treating patients undergoing active ICI therapy as potential immunocompromised hosts due to possible immune dysregulation related to ICI therapy.

Potential PD-1 inhibitor immune dysregulation as a risk factor for Listeria monocytogenes bacteremia and meningitis

As immune checkpoint inhibitor (ICI) therapy becomes increasingly popular for the treatment of cancer, there is a growing body of literature on opportunistic infections associated with ICI therapy. Pembrolizumab binds specifically to the PD-1 receptor on T cells, preventing PD-1’s interaction with PD-L1 and PD-L2. This blockade interrupts the inhibitory signal and restores a T cell’s ability to recognize and attack tumor cells. We present a case of invasive Listeria infection associated with ICI therapy. The case also suggests treating patients undergoing active ICI therapy as potential immunocompromised hosts due to possible immune dysregulation related to ICI therapy.

Verification of a Rapid Analytical Method for the Qualitative Detection of Listeria spp. and Listeria monocytogenes by a Real-Time PCR Assay according to EN UNI ISO 16140-3:2021.

Microbial contamination and foodborne infections are a significant global public health concern. For this reason, the detection, monitoring, and characterization of pathogens represent a significant challenge in quality control settings. Standard approaches, such as culture methods and biochemical tests, are known to be very time-consuming and intensive. Conversely, molecular technologies based on the genomic identification of bacteria are quick and low-cost. Listeria monocytogenes is an opportunistic pathogen and a major concern especially in food industries. It is important to understand and implement multiple quality control measures to control Listeria infection risk and prevent the contamination of products. Standardized detection and confirmation tests such as the API Listeria test, MALDI-TOF MS, and PCR analysis are available. The aim of our work is to provide a specific molecular method, designed according to the EN UNI ISO 16140-3:2021, for the specific detection, monitoring, and characterization of Listeria spp. and Listeria monocytogenes contamination. The verification of this new rapid approach by real-time PCR (qPCR) overcomes the limitations of culture-based techniques, meeting all the verification criteria required by ISO guidelines, including implementation and item confirmation. This system offers a powerful approach to the real-time assessment of food safety, useful for industry self-monitoring and regulatory inspection.

Fractional mathematical model of Listeria infection caused by pre-cooked package food

This article introduces a novel mathematical approach for modeling and analyzing Listeria infection dynamics by considering a system of fractional-order differential equations to understand the complexities. The homotopy perturbation general transform method (HPGTM) is applied to derive approximate solutions for the fractional-order Listeria infection model to obtain valuable insights. The obtained numerical and graphical solutions are rigorously analyzed to explore the effect of fractional orders on the dynamics of Listeria infections. Furthermore, we explore the existence, uniqueness, and stability properties of the solutions, unveiling the critical parameters influencing infection spread and persistence.

Revolutionizing the virulent protein Internalin a in Listeria monocytogenes and designing multi epitope-based vaccine via immunoinformatic approaches

ABSTRACT This study addresses the crucial protein Internalin A in the development of a possible vaccination against Listeria monocytogenes. A meticulous in silico strategy was used which included physiochemical analysis, epitope prediction, and molecular interaction studies. Computational techniques shed light on potential development of a vaccine candidate against Listeria, with a focus on the Internalin A protein along with its immune simulations. Insights into molecular interactions and physiochemical features aid in understanding of prospective Listeria vaccine candidates. Ultimately, the computational analysis in this study sets the groundwork for the creation of a possible vaccination against Listeria. The discovered epitopes and insights into molecular interactions are useful for experimental validation. In vitro and in vivo investigations should be conducted in the future to confirm the effectiveness of these anticipated epitopes. These findings advanced our understanding of vaccine design by providing insights into battling Listeria infections and perhaps guiding tactics for other diseases.

A review of the literature of Listeria monocytogenes in Africa highlights breast milk as an overlooked human source.

According to the latest WHO estimates (2015) of the global burden of foodborne diseases, Listeria monocytogenes is responsible for one of the most serious foodborne infections and commonly results in severe clinical outcomes. The 2013 French MONALISA prospective cohort identified that women born in Africa has a 3-fold increase in the risk of maternal neonatal listeriosis. One of the largest L. monocytogenes outbreaks occurred in South Africa in 2017-2018 with over 1,000 cases. Moreover, recent findings identified L. monocytogenes in human breast milk in Mali and Senegal with its relative abundance positively correlated with severe acute malnutrition. These observations suggest that the carriage of L. monocytogenes in Africa should be further explored, starting with the existing literature. For that purpose, we searched the peer-reviewed and grey literature published dating back to 1926 to date using six databases. Ultimately, 225 articles were included in this review. We highlighted that L. monocytogenes is detected in various sample types including environmental samples, food samples as well as animal and human samples. These studies were mostly conducted in five east African countries, four west African countries, four north African countries, and two Southern African countries. Moreover, only ≈ 0.2% of the Listeria monocytogenes genomes available on NCBI were obtained from African samples, contracted with its detection. The pangenome resulting from the African Listeria monocytogenes samples revealed three clusters including two from South-African strains as well as one consisting of the strains isolated from breast milk in Mali and Senegal and, a vaginal post-miscarriage sample. This suggests there was a clonal complex circulating in Mali and Senegal. As this clone has not been associated to infections, further studies should be conducted to confirm its circulation in the region and explore its association with foodborne infections. Moreover, it is apparent that more resources should be allocated to the detection of L. monocytogenes as only 15/54 countries have reported its detection in the literature. It seems paramount to map the presence and carriage of L. monocytogenes in all African countries to prevent listeriosis outbreaks and the related miscarriages and confirm its association with severe acute malnutrition.

Temporal, spatial and space-time distribution of infections caused by five major enteric pathogens, Ontario, Canada, 2010-2017.

In Canada, enteric diseases pose substantial health and economic burdens. The distribution of these diseases is uneven across both geography and time and understanding these patterns is therefore important for the prevention of future outbreaks. We evaluated temporal, spatial and space-time clustering of laboratory-confirmed cases of Campylobacter spp. (n = 28,728), non-typhoidal Salmonella spp. (n = 22,640), Shiga toxin-producing Escherichia coli (STEC; n = 1340), Yersinia spp. (n = 1674) and Listeria monocytogenes (n = 471) infections, reported between 2010 and 2017 inclusive in Ontario, the most populous province in Canada (population ~ 13,500,000 in 2016). For each enteric pathogen, we calculated the mean incidence rates (IRs) for Ontario's 35 public health unit (PHU) areas and visualized them using choropleth maps. We identified temporal, spatial and space-time high infection rate clusters using retrospective Poisson scan statistics. Campylobacter and Salmonella infections had the highest IRs, while Listeria infections had the lowest. Campylobacter, Salmonella, STEC and Listeria mostly clustered temporally in the spring/summer and sometimes extended into fall, while Yersinia showed a less clear seasonal pattern. The IR visualizations and spatial and space-time scan statistics showed geographic heterogeneity of infection rates with high infection rate clusters detected mainly in PHUs across the southwestern and central-western regions of Ontario for Campylobacter, Salmonella and STEC infections, and mainly in PHUs located in the central-eastern regions for Yersinia and Listeria. A high proportion of cases in some of the significant Salmonella, STEC and Listeria infection clusters were linked to disease outbreaks. Results from this study will inform heightened public health surveillance, and prevention and control programmes, in populations and regions of high infection rates. Further research is needed to determine the pathogen-specific socioeconomic, environmental and agricultural risk factors that may be related to the temporal and spatial disease patterns we observed in our study.

Ulcerative colitis complicated with Listeria meningitis: A case report

Ulcerative colitis complicated with Listeria meningitis: A case report