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Trends in Microbiology Aug 2023The nasopharynx is an important microbial reservoir for the emergence and spread of antibiotic-resistant organisms. The nasopharyngeal resistome is an extensive,... (Review)
Review
The nasopharynx is an important microbial reservoir for the emergence and spread of antibiotic-resistant organisms. The nasopharyngeal resistome is an extensive, adaptable reservoir of antibiotic-resistance genes (ARGs) within this niche. Metagenomic sequencing decodes the genetic material of all organisms within a sample using next-generation technologies, permitting unbiased discovery of novel ARGs and associated mobile genetic elements (MGEs). The challenges of sequencing a low-biomass bacterial sample have limited exploration of the nasopharyngeal resistome. Here, we explore the current understanding of the nasopharyngeal resistome, particularly the role of MGEs in propagating antimicrobial resistance (AMR), explore the advantages and limitations of metagenomic sequencing technologies and bioinformatic pipelines for nasopharyngeal resistome analysis, and highlight the key outstanding questions for future research.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Genes, Bacterial; Nasopharynx; Metagenomics
PubMed: 36967247
DOI: 10.1016/j.tim.2023.02.008 -
Molecular Oncology Feb 2024Drug resistance represents a major limitation to the long-term efficacy of anti-cancer treatments. The commonly accepted view is that the selection of inheritable...
Drug resistance represents a major limitation to the long-term efficacy of anti-cancer treatments. The commonly accepted view is that the selection of inheritable genetic mechanisms governs the development of secondary resistance. However, compelling evidence suggests an important role for adaptive cell plasticity and non-genetic mechanisms in the development of therapy resistance. The two phenomena are not mutually exclusive and the interplay between genetic and non-genetic mechanisms may affect tumor evolution during treatment. A broader characterization of the genetic and non-genetic mechanisms of drug resistance may pave the way for more precise and effective therapeutic strategies to overcome resistance.
Topics: Humans; Neoplasms; Drug Resistance; Epigenesis, Genetic; Drug Resistance, Neoplasm
PubMed: 38308461
DOI: 10.1002/1878-0261.13601 -
Critical Reviews in Oncology/hematology Dec 2023Cancer progression is a dynamic process of continuous evolution, in which genetic diversity and heterogeneity are generated by clonal and subclonal amplification based... (Review)
Review
Cancer progression is a dynamic process of continuous evolution, in which genetic diversity and heterogeneity are generated by clonal and subclonal amplification based on random mutations. Traditional cancer treatment strategies have a great challenge, which often leads to treatment failure due to drug resistance. Integrating evolutionary dynamics into treatment regimens may be an effective way to overcome the problem of drug resistance. In particular, a potential treatment is adaptive therapy, which strategy advocates containment strategies that adjust the treatment cycles according to tumor evolution to control the growth of treatment-resistant cells. In this review, we first summarize the shortcomings of traditional tumor treatment methods in evolution and then introduce the theoretical basis and research status of adaptive therapy. By analyzing the limitations of adaptive therapy and exploring possible solutions, we can broaden people's understanding of adaptive therapy and provide new insights and strategies for tumor treatment.
Topics: Humans; Drug Resistance, Neoplasm; Neoplasms; Treatment Failure
PubMed: 37898477
DOI: 10.1016/j.critrevonc.2023.104192 -
Frontiers in Cellular and Infection... 2024
Topics: Virulence Factors; Anti-Bacterial Agents; Drug Resistance, Bacterial; Bacteria; Virulence
PubMed: 38510958
DOI: 10.3389/fcimb.2024.1387087 -
The Lancet. Planetary Health Jul 2023Antibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of...
BACKGROUND
Antibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of such factors is crucial to explain heterogeneity in ABR rates observed across space, time, and species and antibiotics.
METHODS
We analysed count data of clinical isolates from 51 countries over 2006-19 for thirteen drug-bacterium pairs taken from the ATLAS database. We characterised ABR spatial and temporal patterns and used a mixed-effect negative binomial model, accounting for country-year dependences with random effects, to investigate associations with potential drivers, including antibiotic sales, economic and health indicators, meteorological data, population density, and tourism.
FINDINGS
ABR patterns were strongly country and drug-bacterium pair dependent. In 2019, median ABR rates ranged from 6·3% (IQR 19·7% [0·5-20·2]) for carbapenem-resistant Klebsiella pneumoniae to 80·7% (41·8% [50·4-92·2]) for fluoroquinolone-resistant Acinetobacter baumannii, with heterogeneity across countries. From 2006 to 2019, carbapenem resistance increased in more than 60% of investigated countries; no global trend was observed for other resistances. Multivariable analyses identified significant associations of ABR with country-level selecting antibiotic sales, but only in fluoroquinolone-resistant-Escherichia coli, fluoroquinolone-resistant-Pseudomonas aeruginosa, and carbapenem-resistant-A baumannii. We also found a correlation between temperature and resistance in Enterobacteriaceae and with the health system quality for all drug-bacterium pairs except Enterococci and Streptococcus pneumoniae pairs. Despite wide consideration of possible explanatory variables, drug-bacterium pair ABR rates still showed unexplained spatial random effects variance.
INTERPRETATION
Our findings reflect the diversity of mechanisms driving global antibiotic resistance across pathogens and stress the need for tailored interventions to tackle bacterial resistance.
FUNDING
Independent research Pfizer Global Medical Grant and ANR Labex IBEID.
Topics: Drug Resistance, Microbial; Anti-Bacterial Agents; Carbapenems; Commerce; Escherichia coli; Fluoroquinolones
PubMed: 37437996
DOI: 10.1016/S2542-5196(23)00127-4 -
Cytokine & Growth Factor Reviews Oct 2023In order to adapt to a higher proliferative rate and an increased demand for energy sources, cancer cells rewire their metabolic pathways, a process currently recognized... (Review)
Review
In order to adapt to a higher proliferative rate and an increased demand for energy sources, cancer cells rewire their metabolic pathways, a process currently recognized as a hallmark of cancer. Even though the metabolism of glucose is perhaps the most discussed metabolic shift in cancer, lipid metabolic alterations have been recently recognized as relevant players in the growth and proliferation of cancer cells. Importantly, some of these metabolic alterations are reported to induce a drug resistant phenotype in cancer cells. The acquisition of drug resistance traits severely hinders cancer treatment, being currently considered one of the major challenges of the oncological field. Evidence suggests that Extracellular Vesicles (EVs), which play a crucial role in intercellular communication, may act as facilitators of tumour progression, survival and drug resistance by modulating several aspects involved in the metabolism of cancer cells. This review aims to gather and discuss relevant data regarding metabolic reprograming in cancer, particularly involving the glycolytic and lipid alterations, focusing on its influence on drug resistance and highlighting the relevance of EVs as intercellular mediators of this process.
Topics: Humans; Extracellular Vesicles; Neoplasms; Cell Communication; Drug Resistance, Neoplasm; Lipids
PubMed: 37225643
DOI: 10.1016/j.cytogfr.2023.05.001 -
Nature Communications Jul 2023Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be...
Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.
Topics: Humans; Drug Resistance, Microbial; Patients
PubMed: 37438338
DOI: 10.1038/s41467-023-39416-2 -
Sensors (Basel, Switzerland) Jul 2023Antibiotics are widely used to treat infectious diseases. This leads to the presence of antibiotics and their metabolic products in the ecosystem, especially in aquatic... (Review)
Review
Antibiotics are widely used to treat infectious diseases. This leads to the presence of antibiotics and their metabolic products in the ecosystem, especially in aquatic environments. In many countries, the growth of pathogen resistance to antibiotics is considered a threat to national security. Therefore, methods for determining the sensitivity/resistance of bacteria to antimicrobial drugs are important. This review discusses the mechanisms of the formation of antibacterial resistance and the various methods and sensor systems available for analyzing antibiotic effects on bacteria. Particular attention is paid to acoustic biosensors with active immobilized layers and to sensors that analyze antibiotics directly in liquids. It is shown that sensors of the second type allow analysis to be done within a short period, which is important for timely treatment.
Topics: Anti-Bacterial Agents; Ecosystem; Bacteria; Drug Resistance, Bacterial; Biosensing Techniques
PubMed: 37514587
DOI: 10.3390/s23146292 -
Haematologica Nov 2023
Topics: Humans; Leukemia, Myeloid, Acute; Drug Resistance, Neoplasm
PubMed: 37165841
DOI: 10.3324/haematol.2023.283099 -
The Lancet. Microbe Nov 2023One Health approaches to address the increasing threat of antimicrobial resistance (AMR) are gaining attention. However, data on the distribution and movement of...
Population structure and antimicrobial resistance among Klebsiella isolates sampled from human, animal, and environmental sources in Ghana: a cross-sectional genomic One Health study.
BACKGROUND
One Health approaches to address the increasing threat of antimicrobial resistance (AMR) are gaining attention. However, data on the distribution and movement of bacteria and their AMR-associated genes between clinical and non-clinical sources are scarce, especially from low-income and middle-income countries. We aimed to analyse Klebsiella isolates from various sources in Ghana and compare the prevalence of AMR with datasets from two other countries.
METHODS
We conducted a cross-sectional genomic One Health study. Multiple clinical, environmental, and animal sources were sampled from 78 locations (eg, hospitals, residential areas, and farms) in and around Tamale, Ghana. Clinical samples were collected through routine screening and in cases of suspected infection between March 15 and Sept 15, 2019, and samples from the wider environment were collected during a dedicated sampling effort between the dates of Aug 19, 2018, and Sept 26, 2019. Sampling locations were approximately evenly distributed from the centre of the city and steadily outwards to capture both rural and urban locations. Samples with positive growth for Klebsiella were included. Isolates of Klebsiella were obtained from the samples using Simmons citrate agar medium and characterised by antimicrobial susceptibility testing and whole-genome sequencing. A comparative analysis with Klebsiella population surveys from Pavia, Italy, and Tromsø, Norway, was performed. AMR-associated and virulence genes were detected, and the population distribution of these genes was studied.
FINDINGS
Of 957 samples collected around Tamale, Ghana, 620 were positive for Klebsiella spp. 573 Klebsiella isolates were successfully sequenced, of which 370 were Klebsiella pneumoniae. Only two hospital isolates were carbapenem-resistant. Extended-spectrum β-lactamase (ESBL) genes were relatively common among the Ghanaian clinical isolates but rare in the environmental samples. Prevalence of ESBL genes in human-hospital disease samples was 64% (14 of 22 isolates) in Ghana and 44% (four of nine isolates) in Italy, and prevalence in human-hospital carriage samples was 7% (eight of 107) in Ghana and 13% (54 of 428) in Italy; the prevalence was higher in human-hospital disease samples than in human-hospital carriage samples in both countries, and prevalence across both samples in both countries was higher than in Norway. Ghanaian isolates showed evidence of high recombination rates (recombination events compared with point mutations [r/m] 9·455) and a considerable accessory gene overlap with isolates from Italy and Norway.
INTERPRETATION
Although several AMR-associated gene classes were observed relatively frequently in non-clinical sources, ESBL, carbapenemase, and virulence genes were predominantly present only in hospital samples. These results suggest that interventions should be focused on clinical settings to have the greatest effect on the prevalence and dissemination of AMR-associated genes.
FUNDING
European Research Council (742158), Academy of Finland EuroHPC grant, Trond Mohn Foundation (BATTALION grant), and Wellcome Trust.
Topics: Animals; Humans; Klebsiella; Anti-Bacterial Agents; Ghana; Cross-Sectional Studies; One Health; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Genomics
PubMed: 37858320
DOI: 10.1016/S2666-5247(23)00208-2