Bacteremia caused by Veillonella parvula: Two case reports and a review of the literature.

Veillonella parvula is a non-motile Gram-negative coccus that forms part of the normal microbiota in several body sites and which has been rarely isolated as cause of infections in human population, particularly in bacteremias. Here we give the overview of characteristics of genus Veillonella and the summary of its role in infections, particularly in bacteremia. We additionally report two patients with bacteremia due to V. parvula. Two sets of blood cultures of each patient yielded a pure culture of an anaerobic microorganism identified as V. parvula by MALDI-TOF MS, and confirmed by 16S rRNA gene sequencing. The two patients were male and one of them had risk factors for anaerobic bacteremia. The isolates were susceptible to most antibiotics and the outcome was successful in both patients. Bacteremia due to V. parvula is still rare. MALDI-TOF MS appear to be an excellent tool for the correct identification of these species.

New anaerobic bacteria causing infection: Bacteremia due to Murdochiellaasaccharolytica.

Murdochiella asaccharolytica is a Gram-positive anaerobic coccus firstly isolated from wound specimens, since then, it was very rarely isolated from human infections. We report the first case of bloodstream infection due to this bacterium in a 90 years-old-man. The patient had a history of B-cell lymphoma and presented with pain and induration of the base of penis along with fever. A blood culture was obtained yielding M. asaccharolytica in pure culture. Only resistance to clindamycin was demonstrated. Treatment with metronidazole was started and the clinical evolution improved with antimicrobial treatment, being discharged after 6 days.

Bacteremia due to Clostridium innocuum: Analysis of four cases and literature review.

Clostridium innocuum is a Gram-positive anaerobic spore-forming bacillus that has been identified as part of the normal intestinal microbiota. This bacterium has been rarely associated with human infections, and only few severe infections have been reported until now. In this work, we report on four patients with bacteremia due to C. innocuum, which were well identified by MALDI-TOF MS. Moreover, a review of the previous published cases of bacteremia due to this anaerobic bacterium has been performed.

An uncommon case of bacteremia caused by Lancefieldella parvula in an oncological patient.

We report an uncommon case of bacteremia due to Lancefieldella parvula isolated in pure culture. We present a 72 year-old-man affected with cancer admitted with abdominal pain due to a parietal rupture of the urinary bladder. After surgical treatment, the patient developed fever and two sets of blood cultures yielded a pure culture of an anaerobic microorganism identified as L. parvula (formerly Atopobium parvulum) by MALDI-TOF MS, and confirmed by 16S rRNA gene sequencing. The isolate was susceptible to all antibiotics and the outcome was finally successful. Bacteremia due to L. parvula is an uncommon disease and, in that case, MALDI-TOF MS was an useful tool for the initial identification.

Bacteremia due to Prevotella oris of probable hepatic origin.

Prevotella species are Gram-negative anaerobic bacilli mainly involved in oral cavity infections. We report a rare case of bacteremia due to P. oris of probable hepatic origin. A 70-year-old man with a history of diabetes mellitus was admitted for general malaise, fever and dyspnea. The patient was admitted to the ICU due to septic shock. Two sets of blood cultures yielded a pure culture of an anaerobic microorganism identified as P. oris by MALDI-TOF MS. The same microorganism was isolated from a hepatic abscess drainage. Only resistance to penicillin was documented. Treatment with piperacillin-tazobactam and levofloxacin was administered, and the patient was discharged following his recovery.

Bacteremia due to Parabacteroides distasonis: Experience with 4 cases.

OBJECTIVE: To report a series of four uncommon cases of bacteremia due to Parabacteroides distasonis. METHODS: We have analyzed the epidemiological characteristics, clinical features, diagnostic methods, treatment and outcome of these patients. RESULTS: Two sets of blood cultures of each patient yielded a pure culture of an anaerobic microorganism identified as P. distasonis by MALDI-TOF MS, and confirmed by 16S rRNA gene sequencing. All patients were male and they had risk factors for anaerobic bacteremia. All isolates were susceptible to metronidazole and the outcome was successful in three patients. CONCLUSIONS: Bloodstream infections due to P. distasonis are still rare. MALDI-TOF MS appear to be an excellent tool for the correct identification.

Misidentification of Phocaeicola (Bacteroides) dorei in two patients with bacteremia.

Phocaeicola (Bacteroides) dorei is a Gram-negative anaerobic bacillus that is rarely isolated from human specimens. Its accurate identification can be hampered by its close taxonomic relationship with Bacteroides vulgatus. We report on two patients with bacteremia due to P. (B.) dorei, which was initially identified as B. vulgatus by MALDI-TOF MS.

Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription.

Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei.

A rare cause of bacteremia due to Porphyromonas asaccharolytica in a patient with necrotizing fasciitis.

Porphyromonas species are Gram-negative anaerobic bacilli mainly involved in human periodontal diseases. We report an uncommon case of bacteremia due to P. asaccharolytica in a patient with necrotizing fasciitis. A 52-year-old woman with a history of diabetes mellitus was admitted for an extensive necrotizing lesion on the left lower limb. After she developed septic shock, two sets of blood cultures were taken. Anaerobic bottles yielded a pure culture of a microorganism initially identified as P. uenonis by MALDI-TOF MS but with a low log score, and a gene sequencing technique was therefore applied, identifying the isolate as P. asaccharolytica. Only resistance to penicillin and clindamycin was documented. Treatment with meropenem was administered, and the patient was discharged following her recovery.

First case of abdominal infection caused by bacteroides fluxus.

Bacteroides fluxus is a Gram-negative anaerobic bacillus isolated from human faeces in healthy individuals. Until now, this bacterium had not been involved in human diseases. We report the first case of abdominal infection due to this microorganism in an elderly patient. A 76-year-old man with a history of chronic pulmonary obstructive disease presented with dyspnea, orthopnea and cough. The clinical evolution worsened with both a colonic ischemia and further diffuse peritonitis of pancreatic origin. Peritoneal fluid was obtained and the culture yielded B. fluxus in pure culture. Resistance to penicillin, amoxicillin-clavulanate, clindamycin and moxifloxacin was documented. Treatment with meropenem + linezolid was started, but the patient finally died due to a multiorganic failure.

Bacteremia caused by Veillonella dispar in an oncological patient.

Veillonella dispar is a Gram-negative anaerobic coccus involved in only a few human diseases. We report the second case of bacteremia due to this microorganism in an elderly patient. A 72-year-old man with a history of bladder cancer presented with diarrhea, vomiting, and fever for 48 hours. After the diagnosis of septic shock, four sets of blood cultures were taken, and three of them yielded V. dispar. Resistance to metronidazole, penicillin, and piperacillin-tazobactam was documented. Treatment with clindamycin was started, and the patient was discharged after improvement in his general condition.

First description of abdominal infection due to Alistipes onderdonkii.

Alistipes spp is a genus of Gram-negative anaerobic rods involved in very few human diseases. We report the first case of abdominal infection due to Alistipes onderdonkii in a 58-year-old man with a history of chronic obstructive pulmonary disease. He presented with abdominal pain and general malaise after retrogastric drainage for a pancreatitis episode a few days earlier. After the diagnosis of diffuse peritonitis with perforation and necrotizing pancreatic collection, abundant pancreatic fluid was drained and yielded the isolation of A. onderdonkii in pure culture. Resistance to penicillin and moxifloxacin was documented for this strain. Treatment with metronidazole was prescribed, and the patient was discharged after improvement of his general condition.

A rare case of bacteremia caused by Propionibacterium (Propionimicrobium) lymphophilum.

Propionibacterium (Propionimicrobium) lymphophilum is a Gram-positive anaerobic rod involved in few human diseases. We report a rare case of bacteremia due to this microorganism in an elderly patient. A 95-year-old woman without a remarkable medical history presented with dyspnea, chest pain and fever for seven days. Blood cultures resulted in isolation of P. lymphophilum. Resistance only to metronidazole was found. Treatment with amoxicillin-clavulanic acid was established, and the patient was discharged and improvement of her general condition was documented.

An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer.

Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery.

The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems.

Nicotinamide inhibits the lysosomal cathepsin b-like protease and kills African trypanosomes.

Nicotinamide, a soluble compound of the vitamin B3 group, has antimicrobial activity against several microorganisms ranging from viruses to parasite protozoans. However, the mode of action of this antimicrobial activity is unknown. Here, we investigate the trypanocidal activity of nicotinamide on Trypanosoma brucei, the causative agent of African trypanosomiasis. Incubation of trypanosomes with nicotinamide causes deleterious defects in endocytic traffic, disruption of the lysosome, failure of cytokinesis, and, ultimately, cell death. At the same concentrations there was no effect on a cultured mammalian cell line. The effects on endocytosis and vesicle traffic were visible within 3 h and can be attributed to inhibition of lysosomal cathepsin b-like protease activity. The inhibitory effect of nicotinamide was confirmed by a direct activity assay of recombinant cathepsin b-like protein. Taken together, these data demonstrate that inhibition of the lysosomal protease cathepsin b-like blocks endocytosis, causing cell death. In addition, these results demonstrate for the first time the inhibitory effect of nicotinamide on a protease.

Compositional and functional analysis of the bacterial community of Mediterranean Leptosols under livestock grazing.

The composition and functioning of soil bacterial communities, as well as their responses to multiple perturbations, are not well understood in the terrestrial ecosystems. Our study focuses on the bacterial community of erosive and poorly developed soils (Haplic Leptosols) in Mediterranean rangelands of Extremadura (W Spain) with different grazing intensities. Leptosols from similar natural conditions were selected and sampled at two depths to determine the soil properties as well as the structure and activity of bacterial communities. As grazing intensified, the soil C and N content increased, as did the number and diversity of bacteria, mainly of fast-growing lineages. Aridibacter, Acidobacteria Gp6 and Gp10, Gemmatimonas, and Segetibacter increased their abundance along the grazing-intensity gradient. Firmicutes such as Romboutsia and Turicibacter from livestock microbiome also increased. In functional terms, the KEGG pathways enriched in the soils with moderate and high grazing intensity were ABC transporters, DNA repair and recombination proteins, the two-component system, and the degradation of xenobiotics. All of these proved to be related to stronger cell division and response mechanisms to environmental stressors such as drought, warming, toxic substances, and nutrient deprivation. Consequently, the bacterial community was affected by grazing, but appeared to adapt and counteract the effects of a high grazing intensity. Therefore, a clearly detrimental effect of grazing was not detected in the bacterial community of the soils studied.

Comprehensive insight into the alterations in the gut microbiome and the intestinal barrier as a consequence of iron deficiency anaemia.

BACKGROUND: Iron deficiency is the top leading cause of anaemia, whose treatment has been shown to deteriorate gut health. However, a comprehensive analysis of the intestinal barrier and the gut microbiome during IDA have not been performed to date. This study aims to delve further into the analysis of these two aspects, which will mean a step forward minimising the negative impact of iron supplements on intestinal health. METHODS: IDA was experimentally induced in an animal model. Shotgun sequencing was used to analyse the gut microbiome in the colonic region, while the intestinal barrier was studied through histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence. Determinations of lipopolysaccharide (LPS) and bacteria-specific immunoglobulins were performed to assess microbial translocation. RESULTS: Microbial metabolism in the colon shifted towards an increased production of certain amino acids, short chain fatty acids and nucleotides, with Clostridium species being enriched during IDA. Structural alterations of the colonic epithelium were shown by histological analysis. RNA-Seq revealed a downregulation of extracellular matrix-associated genes and proteins and an overall underdeveloped epithelium. Increased levels of serum LPS and an increased immune response against dysbiotic bacteria support an impairment in the integrity of the gut barrier during IDA. CONCLUSIONS: IDA negatively impacts the gut microbiome and the intestinal barrier, triggering an increased microbial translocation. This study emphasizes the deterioration of gut health during IDA and the fact that it should be addressed when treating the disease.

Fermented Goat's Milk Contributes to the Recovery of Iron Deficiency Anemia via Modulation of the Gut Microbiome.

Iron deficiency anemia (IDA) is a global public health concern affecting 1.6 billion people worldwide. The administration of iron supplements during the treatment of IDA adversely affects the intestinal barrier function and the composition and functionality of the intestinal microbiome, both of which are already altered during IDA. For this reason, it is of great interest to develop nutritional strategies aimed at alleviating these gut alterations associated with IDA and its treatment. In this sense, fermented goat's milk (FGM) was studied due to its nutritional quality. Our findings showed that in anemic animals the consumption of a FGM-based diet, compared to a standard diet, had positive modulatory effects on the intestinal microbiome. FGM-based diet restored intestinal dysbiosis, the intestinal barrier functionality, and bacterial translocation, contributing to a more efficient recovery of IDA. Therefore, FGM is a useful nutritional tool to ease intestinal alterations occurring during IDA and during its treatment.