Listeriosis Research Articles

Clinical Features and Antibiotic Treatment of Neonatal Listeriosis: A Hospital-Based Study.

To determine the clinical features, laboratory findings, antibiotic treatment, and outcomes of neonatal listeriosis in a specialized tertiary hospital in Wuhan, China. We retrospectively analyzed the medical records of patients diagnosed with neonatal listeriosis at Maternal and Child Health Hospital of Hubei Province from January 2015 to December 2022. Listeriosis was indicated by positive culture for Listeria monocytogenes (LM). A total of 11 cases were included in our study. The incidence rate of neonatal listeriosis was 2.06 per 100,000 live births. Seventy-three percent of the cases were born prematurely, caused early onset sepsis. Respiratory distress (100%) was the most common and earliest symptom, followed by fever (64%) and rashes (27%). The levels of C-reactive protein (CRP) and procalcitonin (PCT) were elevated in 100% of the cases. The median time-to-positivity (TTP) of the culture was 15 hours (range 9-28hours). Of the 11 neonates, 6 were cured, 2 showed improvement, and 3 died, with a mortality rate of 27%. There were statistically significant differences in Apgar score at 5 minutes (p=0.037) and CRP (p=0.025) between the survival group and fatality group. Ampicillin was sensitive to LM isolates and effective for therapy if initiated early. Neonatal listeriosis is a rare but severe infection with a high mortality rate. Early identification and appropriate use of effective antibiotics are particularly critical for achieving positive outcomes. Apgar score and CRP are relevant indices for prognosis. Ampicillin is the first-line therapy and can be empirically administered to neonates suspected of having listeriosis.

Characterization of an Autoinducing Peptide Signal Reveals Highly Efficacious Synthetic Inhibitors and Activators of Quorum Sensing and Biofilm Formation in Listeria monocytogenes.

Bacteria can use chemical signals to assess their local population density in a process called quorum sensing (QS). Many of these bacteria are common pathogens, including Gram-positive bacteria that utilize agr QS systems regulated by macrocyclic autoinducing peptide (AIP) signals. Listeria monocytogenes, an important foodborne pathogen, uses an agr system to regulate a variety of virulence factors and biofilm formation, yet little is known about the specific roles of agr in Listeria infection and its persistence in various environments. Herein, we report synthetic peptide tools that will enable the study of QS in Listeria. We identified a 6-mer AIP signal in L. monocytogenes supernatants and selected it as a scaffold around which a collection of non-native AIP mimics was designed and synthesized. These peptides were evaluated in cell-based agr reporter assays to generate structure-activity relationships for AIP-based agonism and antagonism in L. monocytogenes. We discovered synthetic agonists with increased potency relative to native AIP and a synthetic antagonist capable of reducing agr activity to basal levels. Notably, the latter peptide was able to reduce biofilm formation by over 90%, a first for a synthetic QS modulator in wild-type L. monocytogenes. The lead agr agonist and antagonist in L. monocytogenes were also capable of antagonizing agr signaling in the related pathogen Staphylococcus aureus, further extending their utility and suggesting different mechanisms of agr activation in these two pathogens. This study represents an important first step in the application of chemical methods to modulate QS and concomitant virulence outcomes in L. monocytogenes.

Drug Target Identification for Listeria monocytogenes by Subtractive Genomics Approach

We discover essential enzymes catalyzing critical metabolic reactions as potential drug targets, which may help to fight Listeria infections and their associated secondary infections extensively and effectively. A comparative metabolic pathway approach has been applied to identify and determine putative drug targets against Listeria monocytogenes. For this, enzymes unique to pathogenic pathways of L. monocytogenes EGD-e were determined using the KEGG database. They were further refined by selecting enzymes with sequences non-homologous to the host Homo sapiens and analysing their essentiality to the pathogen’s survival. We report 15 essential pathogen-host non-homologous proteins as putative drug targets that can be exploited for development of specific drug targets or vaccines against multidrug resistant strains of L. monocytogenes. Finally, four essential enzymes from the pathogen: UDP-N-acetylglucosamine 1-carboxyvinyltransferase, Acetate kinase, Phosphate acetyltransferase, and Aspartate kinase were reported as novel putative targets for vaccine and drug development against L. monocytogenes infections. Unravelling novel target proteins and their associated pathways by comparing metabolic pathway analysis between L. monocytogenes EGD-e and host H. sapiens, develops the novelty of the work towards broad spectrum putative drug targets. This research design yields putative drug target critical enzymes that turn out to be fatal to the pathogen without interacting with the host machinery.

The Probiotic Bacillus subtilis MB40 Improves Immunity in a Porcine Model of Listeriosis.

Probiotics for humans and direct-fed microbials for livestock are increasingly popular dietary ingredients for supporting immunity. The aim of this study was to determine the effects of dietary supplementation of Bacillus subtilis MB40 (MB40) on immunity in piglets challenged with the foodborne pathogen Listeria monocytogenes (LM). Three-week-old piglets (n = 32) were randomly assigned to four groups: (1) basal diet, (2) basal diet with LM challenge, (3) MB40-supplemented diet, and (4) MB40-supplemented diet with LM challenge. Experimental diets were provided throughout a 14-day (d) period. On d8, piglets in groups 2 and 4 were intraperitoneally inoculated with LM at 108 CFU/mL per piglet. Blood samples were collected at d1, d8, and d15 for biochemical and immune response profiling. Animals were euthanized and necropsied at d15 for liver and spleen bacterial counts and intestinal morphological analysis. At d15, LM challenge was associated with increased spleen weight (p = 0.017), greater circulating populations of neutrophils (p = 0.001) and monocytes (p = 0.008), and reduced ileal villus height to crypt depth ratio (p = 0.009), compared to non-challenged controls. MB40 supplementation reduced LM bacterial counts in the liver and spleen by 67% (p < 0.001) and 49% (p < 0.001), respectively, following the LM challenge, compared to the basal diet. MB40 supplementation was also associated with decreased circulating concentrations of monocytes (p = 0.007). Altogether, these data suggest that MB40 supplementation is a safe and well-tolerated approach to enhance immunity during systemic Listeria infection.

Fatal neonatal listeriosis following L. monocytogenes horizontal transmission highlights neonatal susceptibility to orally acquired listeriosis

We report a case of fulminant fatal neonatal listeriosis due to horizontal transmission of Listeria monocytogenes (Lm) in a neonatal double room. Genomic analyses reveal a close genetic relationship between clinical isolates, supporting cross-contamination. Oral inoculation experiments in adult and neonatal mice show that neonates are susceptible to a low Lm inoculum and that this susceptibility results from the immaturity of the neonatal gut microbiota. Infected neonates should therefore be isolated for as long as they shed Lm in their feces to avoid horizontal transmission and its dire consequences.

Splicing of ultraconserved poison exon elements in RNA binding proteins reprograms the T effector immune response

Abstract Our current understanding of pathways governing the strength and longevity of T cell mediated immune responses primarily focuses on transcriptional and epigenetic changes. However, our prior work demonstrated that optimal T cell effector function is also dependent on RNA binding proteins (RBPs) that carry out post-transcriptional RNA splicing and polyadenylation. Here, we find that a specific family of RBPs, serine- and arginine-rich (SR) RBPs, are significantly upregulated by T cell activation and required for CD8 +T cell mediated responses. SR transcripts contain ultraconserved poison exon (PE) elements that are alternatively spliced and introduce premature stop codons that trigger nonsense-mediated decay. We show that differential splicing of specific RBP PE regions is both induced by TCR stimulation and required for CD8 +T cell activation in both human and mouse. Further, we demonstrate that PEs are cell-state associated by using single-cell RNA sequencing analysis of splicing changes across mouse thymic T cell subsets, in CD8 +T cells over the course of an acute Listeria infection, as well as in human lymphoblastic leukemia, atherosclerosis, and melanoma patient T cells. CRISPR-Cas9 mediated deletion of the PE element of SR-like RBP Tra2β in mouse T effector cells during influenza infection resulted in a significant increase in proliferating and surviving T cells and altered the splicing pattern of critical cell survival, proliferation, and adhesion genes. In total, our work demonstrates a fundamental role for alternatively spliced ultraconserved elements in defining T cell states, controlling T effector-mediated immunity, and altering the T cell response in pathologic conditions. This work was supported in part by NIH grants AI136955 and R21AI139891 awarded to A.T.V, institutional support, and Boehringer Ingelheim endowed Chair in Immunology.

Listeria outbreaks cause maternal and perinatal mortality and morbidity: we must do better.

Listeria outbreaks cause maternal and perinatal mortality and morbidity: we must do better.

Pemphigus foliaceus complicated with Listeria monocytogenes infection and meningitis.

Pemphigus foliaceus complicated with Listeria monocytogenes infection and meningitis.

Adjunctive dexamethasone treatment in adults with listeria monocytogenes meningitis: a prospective nationwide cohort study

A French cohort study described a detrimental effect of adjunctive dexamethasone treatment in listeria meningitis. Based on these results guidelines recommend not to use dexamethasone if L.monocytogenes is suspected or stop dexamethasone when the pathogen is detected. We studied clinical characteristics, treatment regimens and outcome of adults with Listeria monocytogenes meningitis in a nationwide cohort study on bacterial meningitis. We prospectively assessed adults with community-acquired L.monocytogenes meningitis in the Netherlands between Jan 1, 2006, and July 1, 2022. We identified independent predictors for an unfavourable outcome (Glasgow Outcome Scale score 1 to 4) and mortality by logistic regression. 162 out of 2664 episodes (6%) of community-acquired bacterial meningitis episode were caused by L.monocytogenes in 162 patients. Adjunctive dexamethasone 10mg QID was started with the first dose of antibiotics in 93 of 161 patients (58%) and continued for the full four days in 83 (52%) patients. Different doses, duration or timing of dexamethasone were recorded in 11 patients (7%) and 57 patients (35%) did not receive dexamethasone. The case fatality rate was 51 of 162 (31%) and an unfavourable outcome occurred in 91 of 162 patients (56%). Age and the standard regimen of adjunctive dexamethasone were independent predictors for an unfavourable outcome and mortality. The adjusted odds ratio of dexamethasone treatment for unfavourable outcome was 0.40 (95% confidence interval 0.19-0.81). Adjunctive dexamethasone is associated with an improved outcome in patients with L.monocytogenes meningitis and should not be withheld if L.monocytogenes is suspected or detected as causative pathogen. European Research Council and Netherlands Organisation for Health Research and Development.

La listeriosi neonatale e materno-fetale

Listeriosis is a foodborne condition associated with the ingestion of food contaminated by Listeria monocytogenes that can cause serious health consequences in neonates and pregnant women. In these groups the incidence of the disease is higher due to the relative immunocompromised state and the particular Listeria monocytogenes tropism for the placenta. The paediatrician and the neonatologist must therefore be able to recognize the signs and symptoms of the disease promptly so as to set up an adequate treatment according to the most recent international guidelines. This article provides epidemiological data and describes the pathophysiology and clinical manifestations of maternal-foetal and neonatal listeriosis, as well as the therapeutic indications according to very recent recommendations.

Spontaneous bacterial peritonitis by Listeria monocytogenes. A rare case and literature review

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascites and a common complication in patients with cirrhosis, associated with a high morbidity and mortality rate. Gram-negative Enterobacteriaceae bacteria are usually the major pathogens involved in SBP, with Klebsiella pneumoniae accounting for 50% of these. Individuals with chronic liver and /or kidney disease associated with long-standing ascites are predisposed to SBP. Nosocomial SBP presents most commonly a poorer outcome. Although Listeria monocytogenes peritonitis is a relatively rare focal manifestation of Listeria infection, its incidence is increasing. It is associated with a mortality rate approaching 30% in cases of systemic involvement, despite first-line therapy. To our knowledge, this is the first case of L.monocytogenes-associated SBP described in Italy. Clinicians should be aware of the uncommon agents of SBP, such as Listeria, because, if diagnosed early, early antibiotic administration is crucial in minimizing adverse outcomes.

A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function

Mature T cells must discriminate between brief interactions with self-peptides and prolonged binding to agonists. The kinetic proofreading model posits that certain T-cell antigen receptor signaling nodes serve as molecular timers to facilitate such discrimination. However, the physiological significance of this regulatory mechanism and the pathological consequences of disrupting it are unknown. Here we report that accelerating the normally slow phosphorylation of the linker for activation of T cells (LAT) residue Y136 by introducing an adjacent Gly135Asp alteration (LATG135D) disrupts ligand discrimination in vivo. The enhanced self-reactivity of LATG135D T cells triggers excessive thymic negative selection and promotes T-cell anergy. During Listeria infection, LATG135D T cells expand more than wild-type counterparts in response to very weak stimuli but display an imbalance between effector and memory responses. Moreover, despite their enhanced engagement of central and peripheral tolerance mechanisms, mice bearing LATG135D show features associated with autoimmunity and immunopathology. Our data reveal the importance of kinetic proofreading in balancing tolerance and immunity.

Study of bacteria Listeria monocytogenes in spontaneous aborted women in Salah Al-deen province

This study was performed between January 2013 to the end of June 2013, involving 94 spontaneous aborted women at 15-45 years who attended TGH in Salah Al-deen province. They were examined and taking placental pits and cervical swabs. For diagnosis, used Gram staining, cultures, biochemical tests, API system and molecular technique including polymerase chain reaction (PCR).&#x0D; The spontaneous aborted women with Listeria infection was 13 (13.82%) out of 94 aborted women, while 81(81.86%) of aborted women had other causes of abortion. The most affected age group with Listeria infection was 25 – 34 years old represented 7 (53.84%) aborted women. The most infected patients from rural area was 61.53%, while in urban was 38.46%. The most aborted women with Listeria infection were had previous abortions within first trimester (less than 12 weeks of gestational age) were 8 (100%) cases. The pathogens isolated from placenta pits and cervical swabs was Listeria monocytogenes represented 11(37.93%) out of 29 isolated pathogens, while Listeria ivanovii was 2 (6.80%). PCR was used for detection of virulence associated gene of Listeria monocytogenes including hly A which had been found to be amplifying of their DNA fragments. The PCR products showed the eleven isolates of Listeria monocytogenes had the hly A gene

Presentation and outcomes of Listeria-affected pregnancies in Johannesburg tertiary hospitals: A 2-year review.

To describe maternal risk factors, presentations, peripartum findings, and pregnancy outcomes in Listeria monocytogenes-infected women. A retrospective descriptive case review. The records of 51 pregnant women infected with listeriosis who delivered infants between February 1, 2016 and February 28, 2018 at three academic hospitals in Johannesburg, South Africa, were included. The diagnosis of listeriosis was made on maternal/neonatal-sampled blood or tissue cultures. Forty-eight (82.3%) Listeria infections of maternal and neonatal listeriosis were diagnosed on blood culture. The median gestational age at diagnosis was at a preterm gestation of 33 (20-43) weeks. Twenty-eight women (54.9%) had normal vaginal deliveries. Precipitous labor was described in 18 (39%) of these women. Fetal distress was the indication for cesarean section in 22 (41.2%) women. Meconium-stained amniotic fluid was found in 21 (61.7%) women at the time of delivery. The category of very low birth weight had 14 (27.4%) neonates with an Apgar score of less than 7 at 5min. Maternal morbidities included chorioamnionitis (3 [5.8%]) and puerperal infections (7 [13.7%]). The HIV-positive anemic women had a tendency towards listerial infections. Symptoms of listeriosis were non-specific and diagnosis was detected on blood culture sampling. Risk factors included HIV seropositivity and were associated with puerperal infections and anemia.

Diagnostic predictive factors in listeria meningitis

The purpose of this study was to elucidate the diagnostic predictive factors of listeria meningitis. Twenty-eight patients with bacterial meningitis (age; 65.9 ± 14.8 years, 11 female) who were admitted to Chikamori Hospital from October 1, 2006 to December 31, 2021 were included. Bacterial meningitis was defined as cerebrospinal fluids (CSF) pleocytosis with evidence of bacterial infection in CSF or blood. The blood and CSF data were reviewed for analysis. 9 patients were diagnosed as listeria meningitis, 19 patients were in non-listeria meningitis. Multiple logistic regression analysis showed that higher CSF lymphocyte ratio was significantly associated with listeria meningitis (Odds ratio 1.123, 95% Confidence interval 1.006-1.2155, P = 0.039). CSF lymphocyte ratio of 30% or more was found to predict listeria meningitis with a sensitivity of 55.6% and a specificity of 100%. CSF lymphocyte ratio may be useful for differentiating between listeria meningitis and non-listeria meningitis.

Listeria infection in pregnancy: A potentially serious foodborne illness

Listeria infection in pregnancy: A potentially serious foodborne illness

Inhibitory interaction and pharmacological analyses of berries phenolics against Listeria monocytogenes virulent protein internalin B

Background: Traditional plants, their parts, and phytochemicals obtained from them are beneficial for human beings. They are used as potent antimicrobials, but very little research is conducted on the use of traditional medicine against food-borne infection. Different berry plants are rich in phenolic compounds and conventionally known to have many properties such as antioxidants, anti-carcinogenic, anti-inflammatory, anti-bacterial, and anti-diabetics. However, only limited polyphenols are known for their antilisterial effect. The present study aimed to explore the antimicrobial efficacy of phenolic compounds of berries for the treatment of food-borne infection caused by the bacteria Listeria monocytogenes. Materials and Methods: Molecular docking studies employing the SwissDOCK server were performed to evaluate the antimicrobial activity of phenolic compounds obtained from different varieties of berries. Internalin B (InlB), a virulence protein of L. monocytogenes was selected as a target. The absorption, distribution, metabolism, excretion, and toxicity profiling of each test ligand was done through the SwissADME tool. Results: Among all the test ligands, p-coumaric acid, epicatechins, chlorogenic acid, and quercetin showed better binding efficiency with the target protein InlB. The binding energy obtained for quercetin, p-coumaric acid, chlorogenic acid, and epicatechins was-8.93,-8.23,-8.18,-7.58, kcal/mol, respectively. Quercetin and p-coumaric acid were forming 4 H-bonds, whereas chlorogenic acid and epicatechins were forming 3-H bonds inside the binding pocket. Conclusion: In a nutshell, analyses indicated that identified ligands have the potential to block the virulent protein InlB of L. monocytogenes and help combat Listeria infection. These phenolic compounds could be a substitute for synthetic antimicrobials and can be used in food preservation and combat food-borne diseases. However, future in-depth in vitro and in vivo analysis is needed to get more information on these four phenolic ligands of berries.

Listeria monocytogenes septicemia and meningitis induced from immunosuppressant treatments in a patient with neuromyelitis optica spectrum disorder: A case report

Introduction: The aim of this study is to report a fatal case of Listeria monocytogenes septicemia and meningitis complicating azathioprine and glucocorticosteroid treatments during an acute flare of neuromyelitis optica spectrum disorder (NMOSD). Case Report: A Chinese woman who was diagnosed with NMOSD had been on oral prednisolone and azathioprine for about three years. After her fourth relapse, she was treated with high-dose glucocorticosteroids again, and she soon developed an impaired consciousness, headache, and neck stiffness. Her blood culture was positive for L. monocytogenes, and a head computed tomography showed severe hydrocephalus. Although shunt surgery was performed and antibiotics were used, the patient continued to decline and eventually died. Conclusion: We reported the first Asian case of azathioprine-associated L. monocytogenes septicemia in a patient with NMOSD. Physicians should be aware of this serious and potentially lethal side effect when adding multiple immunosuppressants to the regimen of a patient who is already immunocompromised.

DISSEMINATED LISTERIOSIS: A DEADLY TRIPLICATE

DISSEMINATED LISTERIOSIS: A DEADLY TRIPLICATE

Listeria monocytogenes Infection in a 69-year-old Diabetic

Listeria monocytogenes is a gram-positive, rod-shaped facultative anaerobe, often misidentified with Diphtheroids due to sharing similar characteristics. Due to its virulence factor listeriolysin O, it is capable of evading host immune systems and living in extreme environments. This organism often causes listeriosis in pregnant women, newborns, the elderly, or immunocompromised individuals. Therefore, it is crucial to include listeria infection in patients with positive diphtheroids in blood or CSF. We discuss a case of a 69- ear-old Hispanic woman with a history of type 2 diabetes mellitus, hypertension, seizure disorder, and obesity who presented with generalized body aches and fever. Initial blood culture showed diphtheroid on blood culture. In order to distinguish listeria from diphtheroids, longer blood culture inoculation is required. After 48 hours of inoculation, blood culture resulted in L. monocytogenes as the culprit of the patient’ symptoms, contributing to the complex nature of distinguishing between diphtheroid and listeriosis. Therapy was modified to ampicillin at this time. Following antibiotic treatment and negative blood culture, the patient fully recovered from the listeriosis without suspicion of having symptoms of endocarditis and meningitis.