ABSTRACT
Tuberculosis (TB) is the historical leading cause of death by a single infectious agent. The European Regimen Accelerator for Tuberculosis (ERA4TB) is a public-private partnership of 30+ institutions with the objective to progress new anti-TB regimens into the clinic. Thus, robust and replicable results across independent laboratories are essential for reliable interpretation of treatment efficacy. A standardization workgroup unified in vitro protocols and data reporting templates. Time-kill assays provide essential input data for pharmacometric model-informed translation of single agents and regimens activity from in vitro to in vivo and the clinic. Five conditions were assessed by time-kill assays in six independent laboratories using four bacterial plating methods. Baseline bacterial burden varied between laboratories but variability was limited in net drug effect, confirming 2.5 µL equally robust as 100 µL plating. This exercise establishes the foundations of collaborative data generation, reporting, and integration within the overarching Antimicrobial Resistance Accelerator program.
ABSTRACT
Bacterial drug resistance is one of the major challenges to present and future human health, as the continuous selection of multidrug resistant bacteria poses at serious risk the possibility to treat infectious diseases in the near future. One of the infection at higher risk to become incurable is tuberculosis, due to the few drugs available in the market against Mycobacterium tuberculosis. Drug resistance in this species is usually due to point mutations in the drug target or in proteins required to activate prodrugs. However, another interesting and underexplored aspect of bacterial physiology with important impact on drug susceptibility is represented by the changes in transcriptional regulation following drug exposure. The main regulators involved in this phenomenon in M. tuberculosis are the sigma factors, and regulators belonging to the WhiB, GntR, XRE, Mar and TetR families. Better understanding the impact of these regulators in survival to drug treatment might contribute to identify new drug targets and/or to design new strategies of intervention.
Subject(s)
Mycobacterium tuberculosis , Prodrugs , Tuberculosis, Lymph Node , Drug Resistance, Multiple, Bacterial/genetics , Gene Expression Regulation , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/metabolism , Prodrugs/metabolismABSTRACT
The whole-genome sequences of Mycobacterium chimaera strains 850 and 852, which were isolated from two different water samples obtained from a heater-cooler unit at Siena University Hospital (Italy), were determined by combining Nanopore and Illumina technologies. Genomes of both strains 850 and 852 consist of a circular chromosome and five plasmids, with sizes of 6,275,686 bp and 6,453,144 bp, respectively.
ABSTRACT
BACKGROUND: Infertility is estimated to affect approximately 9-30% of reproductive-aged couples. Several conditions involving one or both partners may contribute to infertility. The aim of this study is to evaluate the role of asymptomatic genital tract infections in the outcome of In Vitro Fertilization (IVF) in couples with infertility. METHODS: A total of 285 infertile couples were enrolled in the study. Vaginal/endocervical swabs and semen samples were collected and subjected to microbiological analysis. Spermiograms were carried out on semen specimens, and lactobacilli were quantified in vaginal swabs. Data were associated with IVF results and analysed by using non parametric tests and multivariate analysis. RESULTS: Microbiological analysis showed that 46.3% of couples presented with an asymptomatic genital tract infection. Spermiogram results showed a significantly diminished motility of sperm cells in samples positive to microbiological testing compared to negative specimens. Enterococcus faecalis was the most prevalent species (11.6%) in positive semen samples and was found to negatively affect both sperm morphology (p = 0.026) and motility (p = 0.003). Analysis of genital swabs from females showed that the presence of E. faecalis (p<0.0001), Escherichia coli (p = 0.0123), Streptococcus agalactiae (p<0.0001), and Gardnerella vaginalis (p = 0.0003) was significantly associated to reduced levels of vaginal lactobacilli. Association of microbiological data with IVF outcome showed that 85.7% of IVF+ couples was microbiologically negative, while IVF was successful in just 7.5% of couples infected with E. faecalis and/or U. urealyticum and/or M. hominis (p = 0.02). CONCLUSIONS: The results show the negative impact of E. faecalis on sperm quality and the association of definite bacterial pathogens with reduced levels of vaginal lactobacilli. The presence of E. faecalis and/or U. urealyticum and/or M. hominis in genital samples of infertile couples is predictive for a negative outcome of IVF.
