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Frontiers in Pediatrics 2020Abnormally excessive growth results from perturbation of a complex interplay of genetic, epigenetic, and hormonal factors that orchestrate human growth. Overgrowth... (Review)
Review
Abnormally excessive growth results from perturbation of a complex interplay of genetic, epigenetic, and hormonal factors that orchestrate human growth. Overgrowth syndromes generally present with inherent health concerns and, in some instances, an increased risk of tumor predisposition that necessitate prompt diagnosis and appropriate referral. In this review, we introduce some of the more common overgrowth syndromes, along with their molecular mechanisms, diagnostics, and medical complications for improved recognition and management of patients affected with these disorders.
PubMed: 33194904
DOI: 10.3389/fped.2020.574857 -
Annals of Clinical Microbiology and... Apr 2021Multi-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections... (Review)
Review
Multi-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections has become a major challenge in the field of medicine. In this respect, recent studies have proposed bacteriophage (phage) therapy as a potential alternative against MDR Urinary Tract Infections (UTI) because the resistance mechanism of phages differs from that of antibiotics and few side effects have been reported for them. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are the most common uropathogenic bacteria against which phage therapy has been used. Phages, in addition to lysing bacterial pathogens, can prevent the formation of biofilms. Besides, by inducing or producing polysaccharide depolymerase, phages can easily penetrate into deeper layers of the biofilm and degrade it. Notably, phage therapy has shown good results in inhibiting multiple-species biofilm and this may be an efficient weapon against catheter-associated UTI. However, the narrow range of hosts limits the use of phage therapy. Therefore, the use of phage cocktail and combination therapy can form a highly attractive strategy. However, despite the positive use of these treatments, various studies have reported phage-resistant strains, indicating that phage-host interactions are more complicated and need further research. Furthermore, these investigations are limited and further clinical trials are required to make this treatment widely available for human use. This review highlights phage therapy in the context of treating UTIs and the specific considerations for this application.
Topics: Animals; Bacteria; Bacteriophages; Biofilms; Drug Resistance, Multiple, Bacterial; Glycoside Hydrolases; Host Specificity; Humans; Klebsiella pneumoniae; Phage Therapy; Proteus mirabilis; Urinary Tract Infections; Uropathogenic Escherichia coli
PubMed: 33902597
DOI: 10.1186/s12941-021-00433-y -
The Lancet. Microbe Nov 2022TMexCD1-TOprJ1, which is associated with phenotypic resistance to multiple classes of antibiotics, is a transmissible resistance-nodulation-division (RND) family efflux...
BACKGROUND
TMexCD1-TOprJ1, which is associated with phenotypic resistance to multiple classes of antibiotics, is a transmissible resistance-nodulation-division (RND) family efflux pump. However, the prevalence and genomic and phenotypic characteristics of clinical isolates with this important resistance determinant are poorly understood. In this study, we aimed to survey tmexCD-toprJ among clinical Gram-negative isolates collected from hospitals in China between 1991 and 2020 and characterise tmexCD-toprJ-positive clinical isolates.
METHODS
We conducted online data retrieval and active nationwide surveillance in China to screen tmexCD-toprJ-positive strains. We characterised tmexCD-toprJ-positive clinical strains for their antimicrobial susceptibility, genetic and functional characteristics, and the potential inter-species transmission route of tmexCD-toprJ with whole genome sequencing and bioinformatics analyses. The function of tmexCD-toprJ in Pseudomonas sp and Proteus sp was investigated by tmexD gene knockdown using an isopropylthio-β-galactoside-inducible CRISPR interference system.
FINDINGS
Data retrieval obtained 53 strains carrying tmexCD-toprJ, comprising 32 Pseudomonas spp, 11 Klebsiella pneumoniae, one Aeromonas spp, one Citrobacter freundii, and one uncultured bacterium from diverse niches. 48 (0·64%) of 7517 clinical isolates from China, including seven Klebsiella spp, one Proteus mirabilis, and 40 Pseudomonas spp, carried tmexCD-toprJ. These isolates exhibited multidrug resistance phenotypes and co-harboured resistance genes, such as mcr and carbapenemases genes. tmexCD-toprJ was encoded on both plasmids and chromosomes in all Klebsiella spp that carried plasmid-borne tmexCD-toprJ (n=7), P mirabilis carried chromosome-borne tmexCD-toprJ, and Pseudomonas spp carried either plasmid-borne (n=19) or chromosome-borne (n=21) ones. tmexCD-toprJ had undergone clonal and horizontal transmission among clinical pathogens. Eight different types of genetic context of tmexCD-toprJ were identified, each of which was associated with different mobile elements, including IntI, IS6100, TnAs1-like, ISRor5, ISVsa3, ISCfr-like, Tn5393, and IS222-like, which might facilitate its transmission. Knockdown of tmexD led to a four times decrease in tigecycline minimum inhibitory concentrations in both Pseudomonas spp and Proteus spp.
INTERPRETATION
Our study provides evidence to suggest that tmexCD-toprJ contributes to the antimicrobial resistance phenotypes in different bacterial species. tmexCD-toprJ has disseminated among diverse species of clinical pathogens, which warrants timely monitoring in clinical pathogens.
FUNDING
National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Natural Science Foundation of Jiangsu Province.
Topics: Drug Resistance, Bacterial; Gram-Negative Bacteria; Microbial Sensitivity Tests; Anti-Bacterial Agents; Proteus mirabilis; Multigene Family
PubMed: 36202114
DOI: 10.1016/S2666-5247(22)00221-X -
Cold Spring Harbor Perspectives in... May 2020Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden... (Review)
Review
Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline mutation. Furthermore, outside of the familial setting, somatic variants of occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a mutation. Detection of a germline mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a mutation may highlight new therapeutic opportunities and/or inform therapeutic choices.
Topics: Autism Spectrum Disorder; Biomarkers, Tumor; Genes, Tumor Suppressor; Genetic Testing; Germ-Line Mutation; Hamartoma Syndrome, Multiple; Molecular Targeted Therapy; Neoplasms; PTEN Phosphohydrolase; Phosphatidylinositol 3-Kinases
PubMed: 31615872
DOI: 10.1101/cshperspect.a037127 -
BMJ Case Reports Aug 2019A 62-year-old man was admitted to the emergency department due to fever and acute heart failure. A transthoracic echocardiogram revealed severe aortic valve obstruction....
A 62-year-old man was admitted to the emergency department due to fever and acute heart failure. A transthoracic echocardiogram revealed severe aortic valve obstruction. He was an hepatic transplant recipient and was medicated with everolimus. He underwent mitral and aortic valve replacement with prosthetic valves 4 years ago. Due to his medical background, therapy and clinical presentation, empirical therapy for infective endocarditis was started. Transoesophageal echocardiogram showed severe aortic valve regurgitation but no other findings suggestive of endocarditis. Computed tomography (CT) revealed pulmonary infiltrates compatible with infection and no evidence of septic embolisation. Multiple sets of blood cultures were negative. was isolated in bronchial lavage and antibiotic therapy was adjusted. The patient underwent aortic valve replacement, with no macroscopic findings suggestive of endocarditis. was isolated in the surgically removed valve. Dual antibiotic therapy was successfully administered for 6 weeks.
Topics: Acute Disease; Anti-Bacterial Agents; Aortic Valve Insufficiency; Bronchoalveolar Lavage Fluid; Bronchoscopy; Diagnosis, Differential; Echocardiography, Transesophageal; Endocarditis, Bacterial; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Lung; Male; Middle Aged; Proteus mirabilis; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 31466989
DOI: 10.1136/bcr-2019-230575