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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 -
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 -
Frontiers in Immunology 2024
Topics: Humans; DNA Methylation; Tumor Microenvironment; Immunotherapy; Thoracic Neoplasms; Drug Resistance
PubMed: 38288309
DOI: 10.3389/fimmu.2024.1357278 -
Nature Chemical Biology Oct 2023
Topics: Drug Resistance, Neoplasm; Biochemical Phenomena; Epigenesis, Genetic
PubMed: 37127755
DOI: 10.1038/s41589-023-01323-4 -
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 -
Nature Reviews. Drug Discovery Mar 2024
Topics: Humans; Signal Transduction; Drug Resistance, Neoplasm; Protein Kinase Inhibitors
PubMed: 38336888
DOI: 10.1038/d41573-024-00027-1 -
Methods in Molecular Biology (Clifton,... 2024Antibiotic resistance among pathogenic bacteria is one of the most severe global challenges. It is predicted that over ten million lives will be lost annually by 2050.... (Review)
Review
Antibiotic resistance among pathogenic bacteria is one of the most severe global challenges. It is predicted that over ten million lives will be lost annually by 2050. Phage therapy is a promising alternative to antibiotics. However, the ease of development of phage resistance during therapy is a concern. This review focuses on the possible ways to overcome phage resistance in phage therapy.
Topics: Bacteriophages; Phage Therapy; Bacteria; Drug Resistance, Microbial; Anti-Bacterial Agents
PubMed: 37966611
DOI: 10.1007/978-1-0716-3549-0_23 -
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 -
Malaria Journal Aug 2023Drug resistance is a serious impediment to efficient control and elimination of malaria in endemic areas.
BACKGROUND
Drug resistance is a serious impediment to efficient control and elimination of malaria in endemic areas.
METHODS
This study aimed at analysing the genetic profile of molecular drug resistance in Plasmodium falciparum and Plasmodium vivax parasites from India over a ~ 30-year period (1993-2019). Blood samples of P. falciparum and/or P. vivax-infected patients were collected from 14 regions across India. Plasmodial genome was extracted and used for PCR amplification and sequencing of drug resistance genes in P. falciparum (crt, dhps, dhfr, mdr1, k13) and P. vivax (crt-o, dhps, dhfr, mdr1, k12) field isolates.
RESULTS
The double mutant pfcrt SVMNT was highly predominant across the country over three decades, with restricted presence of triple mutant CVIET from Maharashtra in 2012. High rates of pfdhfr-pfdhps quadruple mutants were observed with marginal presence of "fully resistant" quintuple mutant ACIRNI-ISGEAA. Also, resistant pfdhfr and pfdhps haplotype has significantly increased in Delhi between 1994 and 2010. For pfmdr1, only 86Y and 184F mutations were present while no pfk13 mutations associated with artemisinin resistance were observed. Regarding P. vivax isolates, the pvcrt-o K10 "AAG" insertion was absent in all samples collected from Delhi in 2017. Pvdhps double mutant SGNAV was found only in Goa samples of year 2008 for the first time. The pvmdr1 908L, 958M and 1076L mutations were highly prevalent in Delhi and Haryana between 2015 and 2019 at complete fixation. One nonsynonymous novel pvk12 polymorphism was identified (K264R) in Goa.
CONCLUSIONS
These findings support continuous surveillance and characterization of P. falciparum and P. vivax populations as proxy for effectiveness of anti-malarial drugs in India, especially for independent emergence of artemisinin drug resistance as recently seen in Africa.
Topics: Humans; Plasmodium falciparum; Plasmodium vivax; Genetic Profile; India; Antimalarials; Malaria, Falciparum; Drug Resistance; Malaria, Vivax; Artemisinins; Protozoan Proteins
PubMed: 37582796
DOI: 10.1186/s12936-023-04651-x -
European Journal of Clinical... Dec 2023In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health... (Review)
Review
In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health Organization as a priority one for the need of new therapeutic agents. A. baumannii has the capacity to develop robust biofilms on biotic and abiotic surfaces. Biofilm development allows these bacteria to resist various environmental stressors, including antibiotics and lack of nutrients or water, which in turn allows the persistence of A. baumannii in the hospital environment and further outbreaks. Investigation into therapeutic alternatives that will act on both biofilm formation and antimicrobial resistance (AMR) is sorely needed. The aim of the present review is to critically discuss the various mechanisms by which AMR and biofilm formation may be co-regulated in A. baumannii in an attempt to shed light on paths towards novel therapeutic opportunities. After discussing the clinical importance of A. baumannii, this critical review highlights biofilm-formation genes that may be associated with the co-regulation of AMR. Particularly worthy of consideration are genes regulating the quorum sensing system AbaI/AbaR, AbOmpA (OmpA protein), Bap (biofilm-associated protein), the two-component regulatory system BfmRS, the PER-1 β-lactamase, EpsA, and PTK. Finally, this review discusses ongoing experimental therapeutic strategies to fight A. baumannii infections, namely vaccine development, quorum sensing interference, nanoparticles, metal ions, natural products, antimicrobial peptides, and phage therapy. A better understanding of the mechanisms that co-regulate biofilm formation and AMR will help identify new therapeutic targets, as combined approaches may confer synergistic benefits for effective and safer treatments.
Topics: Humans; Anti-Bacterial Agents; Acinetobacter baumannii; Drug Resistance, Bacterial; Biofilms; Quorum Sensing; Drug Resistance, Multiple, Bacterial
PubMed: 37897520
DOI: 10.1007/s10096-023-04677-8