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Urinary tract infections (UTIs) are the most common bacterial infections around the world. Uropathogenic Escherichia coli (UPEC) is among the main pathogens isolated in UTIs. The rate of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically and conduct to the difficulty to treat UTIs. Due to the rarefaction of new antibiotics molecules, new alternative strategies must be evaluated. Since many years, propolis has demonstrated an interesting antibacterial activity against E. coli . Here, we evaluated its activity added to antibiotics on a panel of UPEC with different resistance mechanisms. Minimal inhibitory concentrations (MICs) and time-kill curves of fosfomycin, ceftriaxone, ertapenem and ofloxacin, with and without propolis, were determined. Significant diminution of the MICs was observed using ceftriaxone or ofloxacin + propolis. Propolis alone had a bacteriostatic activity with time-dependent effect against UPEC. The addition of this nutraceutical improved the effect of all the antibiotics evaluated (except fosfomycin) and showed a synergistic bactericidal effect (fractional inhibitory concentrations index ≤ 0.5 and a decrease ≥ 2 log CFU/mL for the combination of propolis plus antibiotics compared with the antibiotic alone). Propolis is able to restore in vitro antibiotic susceptibility when added to antibiotics against UPEC. This study showed that propolis could enhance the efficiency of antibiotics used in UTIs and could represent an alternative solution.

Urinary tract infections (UTIs) mainly caused by Uropathogenic Escherichia coli (UPEC), are common bacterial infections. Many individuals suffer from chronically recurring UTIs, sometimes requiring long-term prophylactic antibiotic regimens. The global emergence of multi-drug resistant uropathogens in the last decade underlines the need for alternative non-antibiotic therapeutic and preventative strategies against UTIs. The research on non-antibiotic therapeutic options in UTIs has focused on the following phases of the pathogenesis: colonization, adherence of pathogens to uroepithelial cell receptors and invasion. In this review, we discuss vaccines, small compounds, nutraceuticals, immunomodulating agents, probiotics and bacteriophages, highlighting the challenges each of these approaches face. Most of these treatments show interesting but only preliminary results. Lactobacillu s-containing products and cranberry products in conjunction with propolis have shown the most robust results to date and appear to be the most promising new alternative to currently used antibiotics. Larger efficacy clinical trials as well as studies on the interplay between non-antibiotic therapies, uropathogens and the host immune system are warranted., (Copyright © 2020 Loubet, Ranfaing, Dinh, Dunyach-Remy, Bernard, Bruyère, Lavigne and Sotto.)

One strategy to prevent urinary tract infections is the use of natural products such as cranberry (Vaccinium macrocarpon) and propolis. The objective of this study was to evaluate the impact of these products alone and combined on the motility and biofilm formation of a collection of representative uropathogenic Escherichia coli (UPEC). Motility was evaluated by the swarming and swimming capacity of the isolates in presence/absence of cranberry ± propolis. Early and late biofilm formation was observed with the Biofilm Ring test (BioFilm Control) and the crystal violet method. Cranberry alone was seen to have a variable effect on motility and biofilm formation unrelated to bacterial characteristics, but a reduced motility and biofilm formation was observed for all the isolates in the presence of cranberry + propolis. These results suggest that cranberry alone doesn't work on all the E. coli strains and propolis potentiates the effect of cranberry on UPEC, representing a new strategy to prevent recurrent urinary tract infections., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: we declare that Jeremy Ranfaing obtained a PhD fellowship from Nutrivercell. This grant corresponds to a « Bourse CIFRE », a co-funding of academic PhD (half by the University and half by the company). However in this type of grant, all the results obtained during the PhD course belongs to INSERM and University of Montpellier. Nutrivercell had/has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This grant does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors had no financial competing interests with Nutrivercell or other commercial funder.

Uropathogenic Escherichia coli (UPEC), the most prevalent bacteria isolated in urinary tract infections (UTI), is now frequently resistant to antibiotics used to treat this pathology. The antibacterial properties of cranberry and propolis could reduce the frequency of UTIs and thus the use of antibiotics, helping in the fight against the emergence of antibiotic resistance. Transcriptomic profiles of a clinical UPEC strain exposed to cranberry proanthocyanidins alone (190 µg/mL), propolis alone (102.4 µg/mL) and a combination of both were determined. Cranberry alone, but more so cranberry + propolis combined, modified the expression of genes involved in different essential pathways: down-expression of genes involved in adhesion, motility, and biofilm formation, and up-regulation of genes involved in iron metabolism and stress response. Phenotypic assays confirmed the decrease of motility (swarming and swimming) and biofilm formation (early formation and formed biofilm). This study showed for the first time that propolis potentiated the effect of cranberry proanthocyanidins on adhesion, motility, biofilm formation, iron metabolism and stress response of UPEC. Cranberry + propolis treatment could represent an interesting new strategy to prevent recurrent UTI.

Epidemic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is associated with more severe and acute forms of osteomyelitis than healthcare-associated (HA-) MRSA. Although S. aureus is now recognized as a facultative intracellular pathogen, the contribution of osteoblast invasion by CA-MRSA to the pathogenesis of osteomyelitis is unknown. Using an ex vivo model of intracellular infection of human osteoblasts, we demonstrated that CA-MRSA strains of diverse lineages share an enhanced ability to kill infected osteoblasts compared to HA-MRSA. Cytotoxicity comparisons of CA-MRSA isogenic deletion mutants revealed that phenol-soluble modulins (PSMs), a class of membrane-damaging exoproteins that are expressed at higher levels in CA-MRSA than in HA-MRSA, are involved in this osteoblast killing, whereas other major CA-MRSA virulence determinants, the Panton-Valentine leukocidin and alpha-toxin, are not involved. Similarly, functional agr and sarA regulators, which control the expression of PSMs and alpha-toxin, were required for the expression of the intracellular cytotoxic phenotype by CA-MRSA, whereas the saeRS regulator, which controls the expression of alpha-toxin but not PSMs, had no impact on cytotoxicity. Finally, PSM transcript levels determined by quantitative reverse-transcriptase PCR were significantly higher in CA-MRSA than in HA-MRSA strains and associated with cell damage in MRSA-infected osteoblasts. These findings provide new insights into the pathogenesis of severe CA-MRSA osteomyelitis and unravel a novel virulence strategy of CA-MRSA, based on the invasion and subsequent killing of osteoblasts by PSMs acting as intracellular toxins.

Between 1979 and 1989, 108 cases of community acquired pneumonia in non-immunodepressed subjects were admitted to hospital to a specialist chest department. The patient's characteristics were as follows: mean age = 56 (range 14-91), 44 women and 64 men. The causal agent was isolated in 44 cases (40%) of which 4 cases were viral (9% of 44 cases) and 12 were Legionella (27%), pneumococci (SP) 11 cases (25%), Mycoplasma pneumoniae (MP) 8 cases (18%), and Chlamydia 8 cases. The microbacteriological criteria for diagnosis were as follows: significant seroconversion for viruses, MP, Chlamydia, Legionella, bacteriological isolation on blood cultures, and pleural liquid for SP. In 64 cases the bacteriological diagnosis was not established. In this series we note as follows: 1) There did not appear to be any seasonal peak in relation to bacteria isolated, contrary to previous reports, in particular for Legionella. On the other hand viruses occur notably in February and March. 2) Chlamydia were more frequent in individuals living in rural areas; 7 cases out of 8. Whereas amongst the 108 patients 55 were from the country and 34 from the city (16 from institutions and 3 uncertain). In conclusion, if the level of bacteriological identification (IMB) appears weaker than in previous reference series: 51-65%, the diagnostic yield clearly improved in our experience achieving results nearer to the best achievable: 54% of IMB from 48 cases which were recruited between 1985-1989.(ABSTRACT TRUNCATED AT 250 WORDS)

Being little myelotoxic, Bleomycin (BLM) is more and more used in association with other anti-neoplastic drugs; its pulmonary toxicity is not to be overlooked and here is a recall of the risks of pulmonary fibrosis during treatment by BLM. This review is based on a personal experience of 45 cases, of which 6 were cases of respiratory insufficiency. It derived also from a study of the literature which expressed the frequency of respiratory accidents in figures varying from 2 to 94% according to the criteria of tolerance used by the authors. BLM toxicity for the pulmonary tract being important some precautions should be taken in its use: specially supervising aged patients or those with a pastpathological respiratory story; it should particularly concern the functional side, using CO ductance to trace the first signs of toxicity A total dose of 450 mg should not be exceeded.

In the case described, the onset of haemoptysis led to the discovery of a rounded opacity at the left base. All investigations being negative, thoracotomy was performed. The diagnosis could then be made by histology. Bronchopulmonary "tumourlets" are rarely seen (184 cases) masses of epithelial cells which are usually discovered by chance within areas of altered pulmonary tissue. Forms with clinical or radiological manifestations are extremely rare, only 4 other cases having been described. The pathogenesis of these tumours has been the object of recent ultrastructural studies which have shown the relationship which exists between "tumourlet" and carcinoid tumour. It would thus seem reasonable to classify "tumourlets" amongst the tumours of the diffuse endocrine system. The authors nevertheless feel that it would be premature to name them as bronchial carcinoids of tumourlet type. The concept of "tumourlet" as a separate entity should be retained.