Project description:Antibiotic resistance genes (ARGs) and virulence genes (VGs) associated with bacterial pathogens are of great concern in WWTPs, while current knowledge of their profiles and co-occurrence patterns in different time intervals is barely sufficient. Moreover, the impacts of treatment process on ARG/VGs diversity also remain clear. To this end, this study was launched to address the differences of the ARG/VGs diversity between an oxidation ditch (OD) and an membrane bioreactor (MBR) and the co-occurrence patterns in different time intervals using a functional gene array-GeoChip.
Project description:Antimicrobial resistances are emerging as one main threat to worldwide human health and are expected to kill 10 million people by 2050. Intensive livestock husbandry, along with biogas digestate, are considered as one of the biggest ARG reservoirs. Despite major concerns, little information is available on the diversity and abundance of various ARGs in small to large scale pig farms and biogas digestate slurry in Germany, followed by their consequent removal using microfiltration (MF)-nanofiltration (NF) process. Here, we report the identification and quantification of 189 ARGs in raw manure and digestate samples, out of which 66 ARGs were shared among manures and 53 ARGs were shared among both manure and digestate samples. The highest reported total ARG copy numbers in a single manure sampling site was 1.15 × 108 copies/100 µL. In addition, we found the absolute concentrations of 37 ARGs were above 105 copies/100 μL. Filtration results showed that the highly concentrated ARGs (except aminoglycoside resistance ARGs) in feed presented high log retention value (LRV) from 3 to as high as 5 after the MF-NF process. Additionally, LRV below 2 was noticed where the initial absolute ARG concentrations were ≤103 copies/100 μL. Therefore, ARG removal was found to be directly proportional to its initial concentration in the raw manure and in digestate samples. Consequently, some ARGs (tetH, strB) can still be found within the permeate of NF with up to 104 copies/100 μL.
Project description:Using Nanopore sequencing, our study has revealed a close correlation between genomic methylation levels and antibiotic resistance rates in Acinetobacter Baumannii. Specifically, the combined genome-wide DNA methylome and transcriptome analysis revealed the first epigenetic-based antibiotic-resistance mechanism in A. baumannii. Our findings suggest that the precise location of methylation sites along the chromosome could provide new diagnostic markers and drug targets to improve the management of multidrug-resistant A. baumannii infections.
Project description:We used a DNA microarray chip covering 369 resistance types to investigate the relation of antibiotic resistance gene diversity with humans’ age. Metagenomic DNA from fecal samples of 123 healthy volunteers of four different age groups, i.e. pre-school Children (CH), School Children (SC), High School Students (HSS) and Adults (AD) were used for hybridization. The results showed that 80 different gene types were recovered from the 123 individuals gut microbiota, among which 25 were present in CH, 37 in SC, 58 in HSS and 72 in AD. Further analysis indicated that antibiotic resistance genes in groups of CH, SC and AD can be independently clustered, and those ones in group HSS are more divergent. The detailed analysis of antibiotic resistance genes in human gut is further described in the paper DNA microarray analysis reveals the antibiotic resistance gene diversity in human gut microbiota is age-related submitted to Sentific Reports
Project description:In a given bacterial population, antibiotic treatment kills a large portion of the population, while a small, tolerant subpopulation survives. Tolerant cells disrupt the efficacy of antibiotic treatment and increase the likelihood that a population gains antibiotic resistance. Antibiotic tolerance is different from resistance because tolerant cells cannot grow and replicate in the presence of the antibiotic, but when the antibiotic is removed, they begin to propagate. When a population becomes resistant, the antibiotic becomes ineffective, which is a major health concern. Since antibiotic tolerance often leads to antibiotic resistance, we have taken a systems biology approach to examine how regulatory networks respond to antibiotic stress so that cells can survive and recover after antibiotic treatment. We have compared gene expression with and without ampicillin in E. coli.
Project description:Cationic antimicrobial peptides (CAPs) are promising novel alternatives to conventional antibacterial agents, but the overlap in resistance mechanisms between small-molecule antibiotics and CAPs is unknown. Does evolution of antibiotic resistance decrease (cross-resistance) or increase (collateral sensitivity) susceptibility to CAPs? We systematically addressed this issue by studying the susceptibilities of a comprehensive set of antibiotic resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic resistant bacteria frequently showed collateral sensitivity to CAPs, while cross-resistance was relatively rare. We identified clinically relevant multidrug resistance mutations that simultaneously elevate susceptibility to certain CAPs. Transcriptome and chemogenomic analysis revealed that such mutations frequently alter the lipopolysaccharide composition of the outer cell membrane and thereby increase the killing efficiency of membrane-interacting antimicrobial peptides. Furthermore, we identified CAP-antibiotic combinations that rescue the activity of existing antibiotics and slow down the evolution of resistance to antibiotics. Our work provides a proof of principle for the development of peptide based antibiotic adjuvants that enhance antibiotic action and block evolution of resistance.
Project description:We used a DNA microarray chip covering 369 resistance types to investigate the relation of antibiotic resistance gene diversity with humansM-bM-^@M-^Y age. Metagenomic DNA from fecal samples of 123 healthy volunteers of four different age groups, i.e. pre-school Children (CH), School Children (SC), High School Students (HSS) and Adults (AD) were used for hybridization. The results showed that 80 different gene types were recovered from the 123 individuals gut microbiota, among which 25 were present in CH, 37 in SC, 58 in HSS and 72 in AD. Further analysis indicated that antibiotic resistance genes in groups of CH, SC and AD can be independently clustered, and those ones in group HSS are more divergent. The detailed analysis of antibiotic resistance genes in human gut is further described in the paper DNA microarray analysis reveals the antibiotic resistance gene diversity in human gut microbiota is age-related submitted to Sentific Reports The antibiotic resistance gene microarray is custom-designed (Roche NimbleGen), based on a single chip containing 3 internal replicated probe sets of 12 probes per resistance gene, covering the whole 315K 12-plex platform spots.
Project description:Antibiotic treatment typically eliminates a significant portion of a bacterial population, leaving behind a smaller subset of tolerant cells that can survive the treatment. These tolerant cells hinder the effectiveness of the antibiotic, potentially leading to the development of antibiotic resistance within the population. Antibiotic tolerance differs from resistance: tolerant cells are unable to grow or reproduce in the presence of the antibiotic, but they can proliferate once the antibiotic is removed. However, in cases of resistance, the antibiotic loses its efficacy entirely, posing a significant threat to public health. Our study challenges the long-held consensus that persisters are completely dormant and are of one single population. Our results clearly show that persisters are not as dormant as once thought, and multiple populations of persisters form during lethal antibiotic treatment despite the cells being genetically identical. We compared the transcriptome profiles at different time points to investigate the dynamic changes and/or existence of multiple persister subpopulations in response to lethal antibiotic ampicillin (Amp) and ciprofloxacin (Cip) treatment in E. coli.