Treatment of chronic relapsing urinary tract infection with antibiotics selected by AtbFinder.

We report the case of a 46-year-old patient who, after renal cancer surgery, developed a recurrent urinary tract infection that lasted for more than 2 years. Despite repeated antibiotic courses, including broad-spectrum drugs chosen using conventional antibiotic susceptibility testing, multiple reinfections followed. The patient was successfully treated once antibiotics were selected with AtbFinder. Unlike routine antimicrobial susceptibility methods, which select antibiotics effective only against a "lead bacterial pathogen," AtbFinder identifies antibiotics that target the mixture of bacteria at the infection site. This case demonstrates the ability of AtbFinder to successfully select antibiotics for the treatment of relapsing urinary tract infections.

AAV-mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response.

Liver metastasis is the main cause of colorectal cancer (CRC)-related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long-term daily administrations of recombinant DNase I, we have developed an adeno-associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV-mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV-DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV-DNase I and AAV-null treatments. Our data suggest that AAV-mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.

Bacterial DNA induces the formation of heat-resistant disease-associated proteins in human plasma.

Our study demonstrated for the first time that bacterial extracellular DNA (eDNA) can change the thermal behavior of specific human plasma proteins, leading to an elevation of the heat-resistant protein fraction, as well as to de novo acquisition of heat-resistance. In fact, the majority of these proteins were not known to be heat-resistant nor do they possess any prion-like domain. Proteins found to become heat-resistant following DNA exposure were named "Tetz-proteins". Interestingly, plasma proteins that become heat-resistant following treatment with bacterial eDNA are known to be associated with cancer. In pancreatic cancer, the proportion of proteins exhibiting eDNA-induced changes in thermal behavior was found to be particularly elevated. Therefore, we analyzed the heat-resistant proteome in the plasma of healthy subjects and in patients with pancreatic cancer and found that exposure to bacterial eDNA made the proteome of healthy subjects more similar to that of cancer patients. These findings open a discussion on the possible novel role of eDNA in disease development following its interaction with specific proteins, including those involved in multifactorial diseases such as cancer.

Draft Genome Sequence of Chryseobacterium mucoviscidosis sp. nov. Strain VT16-26, Isolated from the Bronchoalveolar Lavage Fluid of a Patient with Cystic Fibrosis.

We report here the draft genome sequence of Chryseobacterium mucoviscidosis VT16-26, a novel bacterium isolated from the lungs of a patient with cystic fibrosis. The genome was composed of 4,403,956 bp and had 36.2% G+C content. We detected 4,048 genes with predicted protein-coding functions, including those associated with antibiotic resistance and virulence.

Complete Genome Sequence of Kluyvera intestini sp. nov., Isolated from the Stomach of a Patient with Gastric Cancer.

We report here an update to the draft genome sequence of Kluyvera intestini sp. nov. strain GT-16, generated using MinION long-read sequencing technology. The complete genome sequence of the human-derived strain GT-16 measured 5,768,848 bp. An improved high-quality complete genome sequence provides insights into the mobility potential of resistance genes in this species.

Draft Genome Sequence of a Strain of Bacillus intestinalis sp. nov., a New Member of Sporobiota Isolated from the Small Intestine of a Single Patient with Intestinal Cancer.

We report here the draft genome sequence of Bacillus intestinalis strain 1731, a novel spore-forming bacterium isolated from the small intestine of a patient with intestinal cancer. The genome comprised 4,047,276 bp, with 43.9% G+C content. There were 3,913 predicted protein-coding genes, including those associated with antibiotic resistance and virulence.

In vitro activity of a novel compound, Mul-1867, against clinically significant fungi Candida spp. and Aspergillus spp.

There is an urgent need for new antifungal compounds to treat various types of fungal infections, including pulmonary infections. This study was designed to investigate the potency of a novel compound (Mul-1867) against Candida spp. and Aspergillus spp. isolated from patients with fungal pneumonia, cystic fibrosis and chronic obstructive pulmonary disease. Mul-1867 was highly effective against susceptible control strains as well as resistant clinical isolates, with minimum fungicidal concentrations (MFCs) varying from 0.06 µg/mL to 0.5 µg/mL. It was also highly effective against pre-formed 48-h-old biofilms formed by yeasts and moulds. The half-minimal biofilm eradication concentration (MBEC50) was equal to the MFC. The minimum biofilm eradication concentration to eliminate 90% of biofilms (MBEC90) varied from 1 × to 4 × MFC. Scanning electron microscopy revealed morphological changes accompanied by the release of intracellular material from the fungal cells following exposure to Mul-1867. Furthermore, an increased concentration of nucleic acids was found in the medium after 5 min and 20 min of Mul-1867 treatment, indicating leakage of cytoplasmic contents. Overall, these data indicate that Mul-1867 may be a promising inhaled antifungal agent for the treatment and prevention of fungal respiratory infections.

Draft Genome Sequence of the Uropathogenic Herbaspirillumfrisingense Strain ureolyticus VT-16-41.

Herbaspirillum frisingense strain ureolyticus VT-16-41 is a clinical cystitis isolate. Here, we report the draft genome sequence of the uropathogenic H. frisingense strain ureolyticus VT-16-41, which contains various antibiotic resistance genes and virulence factors that enable it to colonize and persist in the urinary tract.

Draft Genome Sequence of Kluyvera intestini Strain GT-16 Isolated from the Stomach of a Patient with Gastric Cancer.

Here, we report the complete genome sequence of the novel, non-spore-forming Kluyvera intestini strain GT-16, isolated from the stomach of a patient with gastric cancer. The genome is 5,868,299 bp in length with a G+C content of 53.0%. It possesses 5,350 predicted protein-coding genes encoding virulence factors and antibiotic resistance proteins.

Complete Genome Sequence of a Novel Bacillus sp. VT 712 Strain Isolated from the Duodenum of a Patient with Intestinal Cancer.

We report here the complete genome sequence of the spore-forming Bacillus sp. strain VT 712 isolated from the duodenum of a patient with intestinal cancer. The genome is 3,921,583 bp, with 37.9% G+C content. It contains 3,768 predicted protein-coding genes for multidrug resistance transporters, virulence factors, and daunorubicin resistance.

Antimicrobial activity of mul-1867, a novel antimicrobial compound, against multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND: There is an urgent need for new antimicrobial compounds to treat various lung infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR-PA). METHODS: We studied the potency of Mul-1867 against MDR-PA isolates from patients with cystic fibrosis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia. The minimal inhibitory concentrations (MICs) and minimum biofilm eliminating concentrations (MBECs), defined as the concentrations of drug that kill 50 % (MBEC50), 90 % (MBEC90), and 100 % (MBEC100) of the bacteria in preformed biofilms, were determined by using the broth macrodilution method. RESULTS: Mul-1867 exhibited significant activity against MDR-PA and susceptible control strains, with MICs ranging from 1.0 to 8.0 µg/mL. Mul-1867 also possesses anti-biofilm activity against mucoid and non-mucoid 24-h-old MDR-PA biofilms. The MBEC50 value was equal to onefold the MIC. The MBEC90 value ranged from two to fourfold the MIC. Moreover, Mul-1867 completely eradicated mature biofilms at the concentrations tested, with MBEC100 values ranging between 16- and 32-fold the MIC. Mul-1867 was non-toxic to Madin-Darby canine kidney (MDCK) cells at concentrations up to 256 µg/mL. CONCLUSION: Overall, these data indicate that Mul-1867 is a promising locally acting antimicrobial for the treatment and prevention of P. aeruginosa infections.

Genomic characterization and assessment of the virulence and antibiotic resistance of the novel species Paenibacillus sp. strain VT-400, a potentially pathogenic bacterium in the oral cavity of patients with hematological malignancies.

BACKGROUND: Paenibacillus sp. strain VT-400, a novel spore-forming bacterium, was isolated from patients with hematological malignancies. METHODS: Paenibacillus sp. strain VT-400 was isolated from the saliva of four children with acute lymphoblastic leukemia. The genome was annotated using RAST and the NCBI Prokaryotic Genome Annotation Pipeline to characterize features of antibiotic resistance and virulence factors. Susceptibility to antibiotics was determined by the Kirby-Bauer disc diffusion method. We used a mouse model of pneumonia to study virulence in vivo. Mice were challenged with 7.5 log10-9.5 log10 CFU, and survival was monitored over 7 days. Bacterial load was measured in the lungs and spleen of surviving mice 48 h post-infection to reveal bacterial invasion and dissemination. RESULTS: Whole-genome sequencing revealed a large number of virulence factors such as hemolysin D and CD4+ T cell-stimulating antigen. Furthermore, the strain harbors numerous antibiotic resistance genes, including small multidrug resistance proteins, which have never been previously found in the Paenibacillus genus. We then compared the presence of antibiotic resistance genes against results from antibiotic susceptibility testing. Paenibacillus sp. strain VT-400 was found to be resistant to macrolides such as erythromycin and azithromycin, as well as to chloramphenicol and trimethoprim-sulphamethoxazole. Finally, the isolate caused mortality in mice infected with ≥8.5 log10 CFU. CONCLUSIONS: Based on our results and on the available literature, there is yet no strong evidence that shows Paenibacillus species as an opportunistic pathogen in immunocompromised patients. However, the presence of spore-forming bacteria with virulence and antibiotic resistance genes in such patients warrants special attention because infections caused by spore-forming bacteria are poorly treatable.

Draft Genome Sequence of Acinetobacter sp. Strain VT-511 Isolated from the Stomach of a Patient with Gastric Cancer.

We report the draft genome sequence of Acinetobacter sp. strain VT-511, which was obtained from the stomach of a patient with gastric cancer. The genome of Acinetobacter sp. VT-511 is composed of approximately 3,416,321 bp and includes 3,214 predicted protein-coding genes.

Complete Genome Sequence of Paenibacillus sp. Strain VT 400, Isolated from the Saliva of a Child with Acute Lymphoblastic Leukemia.

We report here the complete genome sequence of spore-forming Paenibacillus sp. strain VT 400, isolated from the saliva of a child with acute lymphoblastic leukemia. The genome consists of 6,986,122 bp, with a G+C content of 45.8%. It possesses 5,777 predicted protein-coding genes encoding multidrug resistance transporters, virulence factors, and resistance to chemotherapeutic drugs.

Complete Genome Sequence of Bacilli bacterium Strain VT-13-104 Isolated from the Intestine of a Patient with Duodenal Cancer.

We report the complete genome sequence of Bacilli bacterium strain VT-13-104 isolated from the intestine of a patient with duodenal cancer. The genome is composed of 3,573,421 bp, with a G+C content of 35.7%. It possesses 3,254 predicted protein-coding genes encoding multidrug resistance transporters, resistance to antibiotics, and virulence factors.