Fecal microbiota transplantation reduces mouse mortality from Listeria monocytogenes infection.

Listeria monocytogenes (Lm) is a food bacterium with strong pathogenicity which causes infections via the gastrointestinal tract. Mechanisms by which gut microbiota (GM) resist microbial infections have received little attention. Eight-week-old mice were orally inoculated with wild-type Lm EGD-e and fecal microbiota transplantation (FMT) employed. GM richness and diversity of infected mice changed rapidly within 24h. Firmicutes class decreased and Bacteroidetes, Tenericutes and Ruminococcaceae increased significantly. Coprococcus, Blautia and Eubacterium also increased on the 3rd day post-infection. Moreover, GM transplanted from healthy mice reduced mortality of infected mice by approximately 32%. FMT treatment decreased production of TNFα, IFN-γ, IL-1ß and IL-6 relative to PBS treatment. In summary, FMT has potential as a treatment against Lm infection and may be used for bacterial resistance management. Further work is required to elucidate the key GM effector molecules.

A Bacteriophage Cocktail Significantly Reduces Listeria monocytogenes without Deleterious Impact on the Commensal Gut Microbiota under Simulated Gastrointestinal Conditions.

In this study, we examined the effect of a bacteriophage cocktail (tentatively designated as the Foodborne Outbreak Pill (FOP)) on the levels of Listeria monocytogenes in simulated small intestine, large intestine, and Caco-2 model systems. We found that FOP survival during simulated passage of the upper gastrointestinal was dependent on stomach pH, and that FOP robustly inhibited L. monocytogenes levels with effectiveness comparable to antibiotic treatment (ampicillin) under simulated ilium and colon conditions. The FOP did not inhibit the commensal bacteria, whereas ampicillin treatment led to dysbiosis-like conditions. The FOP was also more effective than an antibiotic in protecting Caco-2 cells from adhesion and invasion by L. monocytogenes (5-log reduction vs. 1-log reduction) while not triggering an inflammatory response. Our data suggested that the FOP may provide a robust protection against L. monocytogenes should the bacterium enter the human gastrointestinal tract (e.g., by consumption of contaminated food), without deleterious impact on the commensal bacteria.

Infección por listeria monocytogenes en el embarazo, asociado a desprendimiento de placenta y complicaciones perinatales: reporte de un caso / Listeria monocytogenes infection in pregnancy, associated with placental abruption and perinatal complications: case report

INTRODUCCIÓN la listeriosis, aunque es una infección infrecuente, debe ser considerada en pacientes inmunocomprometidos y gestantes, especialmente en aquellos que consumen alimentos crudos o productos lácteos no pasteurizados, lo que pone en riesgo a un gran número de mujeres embarazadas en países de habla hispana. Es importante que el médico considere su inclusión en los posibles diagnósticos diferenciales cuando la sospecha clínica lo amerite, lo que permitirá hacer un diagnóstico temprano y por lo tanto un tratamiento oportuno, evitando así las posibles complicaciones en el binomio madre-hijo. CASO CLÍNICO clínico multigestante, con embarazo de 33 + 5 semanas, que ingresó a una institución de alto nivel de complejidad en la ciudad de Medellín, Colombia, por síndrome febril asociado a sepsis obstétrica debido a infección intraamniótica por Listeria monocytogenes, que requirió cesárea de urgencia, en donde se evidenció un desprendimiento placentario del 100 % secundario al proceso infeccioso y asociado a complicaciones neonatales. CONCLUSIONES: el diagnóstico de listeriosis gestacional supone un reto clínico por su presentación inespecífica y baja incidencia. Sin embargo, las consecuencias obstétricas arrastran una gran morbilidad de la madre y morbi-mortalidad neonatal, lo que hace de suma importancia que el clínico lo tenga presente en su arsenal diagnóstico, ya que una vez diagnosticado, el tratamiento oportuno tiene desenlaces clínicos favorables.

INTRODUCTION: although listeriosis is a rare infection, it should be considered in immunocompromised patients and pregnancy, especially in those who consume raw food or unpasteurized dairy, which puts a large number of pregnant women in Hispanic countries at risk. It is of special importance for physicians to include listeriosis among possible diagnoses when clinical suspicion arises in order to timely treat it and thus avoid the complications that may occur in the mother-child binomial. CLINICAL CASE: a pregnant woman (33 + 5 weeks) with multiple gestations, was admitted to a high level of complexity institution in the city of Medellín, Colombia, presenting a febrile syndrome associated with obstetric sepsis due to intra-amniotic infection by Listeria monocytogenes, which required emergency cesarean section where a 100 % placental abruption was evidenced secondary to the infectious process and associated with neonatal complications. CONCLUSIONS: The diagnosis of gestational listeriosis is a clinical challenge due to its nonspecific presentation and low incidence. However, the obstetric consequences drag a great maternal morbidity and neonatal morbidity and mortality, which is why it is important for physicians to consider this in the diagnostic arsenal because once diagnosed, the appropriate treatment has favorable clinical outcomes.

CD71+ Erythroid Cells in Human Neonates Exhibit Immunosuppressive Properties and Compromise Immune Response Against Systemic Infection in Neonatal Mice.

Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors CD71+erythroid cells (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45+CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin in vitro. Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to Listeria monocytogenes infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.

Current aspects of listeriosis. / Aspectos actuales de la listeriosis.

The importance of listeriosis is not sufficiently recognised. The general incidence of infection has been stable in recent years, but with an upward trend in people over 65, also in mortality. Listeriosis is a foodborne disease that generally occurs in the form of sporadic cases; however, new molecular typing techniques have revealed the existence of epidemic outbreaks not previously suspected. The disease has a variable incubation period, which is related to the clinical presentation. Bacteraemia and neurolisteriosis are the predominant clinical forms, although at present, the main interest is focused on the management of focal infections and those associated with prosthetic devices. Listeriosis is a significant problem for the food industry, and many countries have introduced legislation to control the incidence of the disease.

Outcomes of neonates with listeriosis supported with extracorporeal membrane oxygenation from 1991 to 2017.

BACKGROUND: Listeriosis may cause severe disease in fetuses and neonates. The outcomes of critically ill neonates with early-onset listeriosis requiring extracorporeal membrane oxygenation (ECMO) from 1975 to 1991 have been reported. OBJECTIVE: To update the characteristics and outcomes of neonates with listeriosis supported by ECMO. STUDY DESIGN: Retrospective study of neonates with culture-proven listeriosis reported to the Extracorporeal Life Support Organization Registry between 1991 and 2017. Comparisons were made between this cohort and the case series from 1975-1991. RESULTS: Twenty-two neonates had culture-proven Listeria monocytogenes infection and required ECMO support. Eight-six percent survived to discharge, compared with 67% in the previous cohort (p = 0.2). The median ECMO duration was 131 h, compared with 209 h in the previous cohort (p = 0.1). Nonsurvivors had a significantly lower pre-ECMO pH (6.91 vs 7.31, p = 0.0006). CONCLUSION: The survival of neonates with listeriosis supported with ECMO is high, supporting the use of ECMO as rescue therapy for this condition.

[Abdominal pain in a man with an endovascular aortic prosthesis]. / Buikpijn bij een man met een vaatprothese in de aorta.

A 79-year-old man with an abdominal aorta aneurysm (AAA) with endovascular repair presented with abdominal pain and inflammation. Although the initial work-up was in favour of an idiopathic inflammatory AAA, FDG-PET imaging showed atypical irregular uptake. Per-operative assessment and culture of pus matter revealed infection by Listeria monocytogenes. Atypical findings on imaging of aortic wall inflammation should alarm the clinician of an infectious aetiology.

Internalin AB-expressing recombinant Lactobacillus casei protects Caco-2 cells from Listeria monocytogenes-induced damages under simulated intestinal conditions.

BACKGROUND: Listeria monocytogenes is an intracellular foodborne pathogen that employs a number of strategies to survive challenging gastrointestinal conditions. It proliferates in the gut and subsequently causes listeriosis in high-risk individuals. Therefore, inhibition of its adherence to the intestinal receptors is crucial in controlling its infection. In this study, the effect of our previously developed recombinant Lactobacillus casei strain expressing invasion protein, Internalin AB of L. monocytogenes (LbcInlAB) on epithelial infection processes of the latter under simulated intestinal conditions was investigated. MATERIALS AND METHODS: The confluent Caco-2 cell monolayer was pre-exposed to different L. casei strains at a multiplicity of exposure (MOE) of 10 for various periods before infection with L. monocytogenes at a multiplicity of infection (MOI) of 10 under simulated intestinal conditions. Subsequently, L. monocytogenes adhesion, invasion, and translocation, cytotoxicity and impact on tight junction integrity of the Caco-2 cells were analyzed. RESULTS: Under the simulated gastrointestinal condition, LbcInlAB showed a significant increase (p<0.0001) in adherence to, invasion and translocation through the Caco-2 cells when compared with the wild type strain. Although LbcInlAB strain exhibited enhanced inhibition of L. monocytogenes, it was not able to displace L. monocytogenes cells already attached to the monolayer. Additionally, pre-exposure to LbcInlAB reduced L. monocytogenes-mediated cytotoxicity and protected the tight junction barrier function. CONCLUSION: The recombinant L. casei expressing InlAB shows potential for use as a prophylactic intervention strategy for targeted control of L. monocytogenes during the intestinal phase of infection.

Conversion of staphylococcal pathogenicity islands to CRISPR-carrying antibacterial agents that cure infections in mice.

Staphylococcus aureus and other staphylococci continue to cause life-threatening infections in both hospital and community settings. They have become increasingly resistant to antibiotics, especially ß-lactams and aminoglycosides, and their infections are now, in many cases, untreatable. Here we present a non-antibiotic, non-phage method of treating staphylococcal infections by engineering of the highly mobile staphylococcal pathogenicity islands (SaPIs). We replaced the SaPIs' toxin genes with antibacterial cargos to generate antibacterial drones (ABDs) that target the infecting bacteria in the animal host, express their cargo, kill or disarm the bacteria and thus abrogate the infection. Here we have constructed ABDs with either a CRISPR-Cas9 bactericidal or a CRISPR-dCas9 virulence-blocking module. We show that both ABDs block the development of a murine subcutaneous S. aureus abscess and that the bactericidal module rescues mice given a lethal dose of S. aureus intraperitoneally.

Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells.

Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer and chronic infections. We show that sprouty 1 and 2 (Spry1/2) molecules regulate the survival and function of memory CD8+ T cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I cells when transferred to mice expressing OVA in their pancreatic ß-islets. To determine the consequence of Spry1/2 deletion on effector and memory CD8+ T cell development and function, we used systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong. Spry1/2 DKO LCMV gp33-specific P14 CD8+ T cells survive contraction better than WT cells and generate significantly more polyfunctional memory T cells. The larger number of Spry1/2 DKO memory T cells displayed enhanced infiltration into infected tissue, demonstrating that absence of Spry1/2 can result in increased recall capacity. Upon adoptive transfer into naive hosts, Spry1/2 DKO memory T cells controlled Listeria monocytogenes infection better than WT cells. The enhanced formation of more functional Spry1/2 DKO memory T cells was associated with significantly reduced mTORC1 activity and glucose uptake. Reduced p-AKT, p-FoxO1/3a, and T-bet expression was also consistent with enhanced survival and memory accrual. Collectively, loss of Spry1/2 enhances the survival of effector CD8+ T cells and results in the formation of more protective memory cells. Deleting Spry1/2 in antigen-specific CD8+ T cells may have therapeutic potential for enhancing the survival and functionality of effector and memory CD8+ T cells in vivo.

Listeriosis during the period 2003-2016.

Listeria monocytogenes can cause invasive disease in immunocompromised patients. We have retrospectively reviewed the clinical characteristics, treatment and evolution of the cases of listeriosis registered at our center during a long period of 14 years. Listeria monocytogenes infection is potentially serious with high mortality. Therefore, a high index of suspicion and early directed antibiotic treatment are needed, especially for immunocompromised patients.

Co-infection with Streptococcus pneumoniae and Listeria monocytogenes in an immunocompromised patient.

A 34-year-old HIV-positive man with a history of chronic substance abuse was admitted with dual infection of Streptococcus pneumoniae and Listeria monocytogenes. Combined bacteraemia with S. pneumoniae and L. monocytogenes is very rare. To the best of our knowledge, this is the first such case documented at our institution and in South Africa. Ampicillin should be added to antibiotic regimens to improve patient outcome if L. monocytogenes infection is suspected. Co-infections that occur with L. monocytogenes may have conflicting antibiotic treatment options. This case report emphasises the need for a good relationship between the local microbiology pathologist and physician to select appropriate antibiotic treatment before definitive results are available.

Diagnosis and Treatment of Listeria monocytogenes Endophthalmitis: A Systematic Review.

PURPOSE: Describe patient characteristics, treatment, and vision outcomes of Listeria monocytogenes endophthalmitis, an exceedingly rare form of listeriosis. METHODS: L. monocytogenes endophthalmitis cases in human adults, located through Medline (32) and from disease surveillance centers (11). L. monocytogenes conjunctivitis and keratitis were excluded. RESULTS: Most cases occurred in 2000-2015 (22/43), and almost all in Europe or North America (40/43). Patients were a median 61 years, 57% male (24/42) and half were immunosuppressed. Median days from entering care to diagnosis was 8 (IQR = 5-17). Only four were exogenous infections. L. monocytogenes was identified in 31/35 of anterior eye fluid samples (89%). Antibiotic regimens varied markedly (mostly ≥3 drugs). At diagnosis, most were blind in the affected eye (85%, 28/33), only a third regained normal vision (12/36). Older patients had poorer outcomes. CONCLUSIONS: Cases increased over time. Diagnostic delays were common and visual impairment often refractory to treatment, especially in older adults. The condition's rarity and variation in treatment makes it difficult to identify optimum therapy.

Lactococcus lactis and Lactobacillus salivarius differently modulate early immunological response of Wistar rats co-administered with Listeria monocytogenes.

In the light of the increasing resistance of bacterial pathogens to antibiotics, one of the main global strategies in applied science is development of alternative treatments, which would be safe both for the host and from the environmental perspective. Accordingly, the aim of this study was to test whether two lactic acid bacteria (LAB) strains, Lactococcus lactis BGBU1-4 and Lactobacillus salivarius BGHO1, could be applied as safe supplements for Listeria infection. Two major research objectives were set: to compare the effects of BGBU1-4 and BGHO1 on early immune response in gut tissue of Wistar rats co-administered with Listeria monocytogenes ATCC19111 and next, to test how this applies to their usage as therapeutics in acute ATCC19111 infection. Intestinal villi (IV), Peyer's patches (PP) and mesenteric lymph nodes (MLN) were used for the analysis. The results showed that BGHO1 increased the mRNA expression of innate immune markers CD14, interleukin (IL)-1ß and tumour necrosis factor (TNF)-α in PP and IV, and, in parallel, caused a decrease of listeriolysin O (LLO) mRNA expression in same tissues. In MLN of BGHO1 treated rats, LLO expression was increased, along with an increase of the expression of OX-62 mRNA and CD69, pointing to the activation of adaptive immunity. On the other hand, in BGBU1-4 treated rats, there was no reduction of LLO mRNA expression and no induction of innate immunity markers in intestinal tissue. Additionally, CD14 and IL-1ß, as well as LLO, but not OX-62 mRNA and CD69 expression, were elevated in MLN of BGBU1-4 treated rats. However, when applied therapeutically, both, BGBU1-4 and BGHO1, lowered Listeria count in spleens of infected rats. Our results not only reveal the potential of LAB to ameliorate Listeria infections, but suggest different immunological effects of two different LAB strains, both of which could be effective in Listeria elimination.

Listeriosis Phytotherapy: A Review Study on the Effectiveness of Iranian Medicinal Plants in Treatment of Listeriosis.

Listeria monocytogenes can be found in many processed foods, raw milk, dairy products, meat and meat products such as sausages, beef and fish products, seafoods, eggs, fruits, and vegetables such as radish and cabbage. This article is a review study on the Iranian medicinal plants applied for treatment of listeriosis. Information of this review article was obtained by searching various key words such as Listeria monocytogenes, medicinal plants, plant extracts and essential oils among scientific articles published in databases of Google scholar, ISI Web of Knowledge, PubMed, Scopus, SID and Magiran. Thyme, German chamomile, great chamomile, yarrow, onion, oregano, nutmeg, sage, sagebrush, hyssop, rosemary, St John's wort, safflower, ajowan, cumin, peppermint, shallot, anise, and parsnip are known antilisteriosis medicinal plants. Bioactive phytochemicals, antioxidants and monoterpenes, sesquiterpene, coumarin, flavonoids, tannins, saponins, alkaloids, and terpenoids are the main ingredients of antilisteriosis medicinal plants.

Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation.

Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states. VIDEO ABSTRACT.