-
Frontiers in Cellular and Infection... 2024
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Microbial; Anti-Infective Agents; Bacterial Infections; Bacteria
PubMed: 38895736
DOI: 10.3389/fcimb.2024.1434140 -
Nature Microbiology Mar 2024Epidemiological knowledge of circulating carbapenem-resistant Klebsiella pneumoniae (CRKP) is needed to develop effective strategies against this public health threat....
Epidemiological knowledge of circulating carbapenem-resistant Klebsiella pneumoniae (CRKP) is needed to develop effective strategies against this public health threat. Here we present a longitudinal analysis of 1,017 CRKP isolates recovered from patients from 40 hospitals across China between 2016 and 2020. Virulence gene and capsule typing revealed expansion of CRKP capsule type KL64 (59.5%) alongside decreases in KL47 prevalence. Hypervirulent CRKP increased in prevalence from 28.2% in 2016 to 45.7% in 2020. Phylogenetic and spatiotemporal analysis revealed Beijing and Shanghai as transmission hubs accounting for differential geographical prevalence of KL47 and KL64 strains across China. Moderate frequency capsule or O-antigen loss was also detected among isolates. Non-capsular CRKP were more susceptible to phagocytosis, attenuated during mouse infections, but showed increased serum resistance and biofilm formation. These findings give insight into CRKP serotype prevalence and dynamics, revealing the importance of monitoring serotype shifts for the future development of immunological strategies against CRKP infections.
Topics: Humans; Animals; Mice; China; Virulence Factors; Klebsiella pneumoniae; Phylogeny; Drug Resistance, Microbial; Carbapenem-Resistant Enterobacteriaceae; Carbapenems
PubMed: 38424289
DOI: 10.1038/s41564-024-01612-1 -
Current Opinion in Microbiology Aug 2023Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic... (Review)
Review
Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic resistance, in particular, is not just a property of individual bacteria or even single-strain populations, but depends heavily on the community context. Collective community dynamics can lead to counterintuitive eco-evolutionary effects like survival of less resistant bacterial populations, slowing of resistance evolution, or population collapse, yet these surprising behaviors are often captured by simple mathematical models. In this review, we highlight recent progress - in many cases, advances driven by elegant combinations of quantitative experiments and theoretical models - in understanding how interactions between bacteria and with the environment affect antibiotic resistance, from single-species populations to multispecies communities embedded in an ecosystem.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Models, Theoretical; Microbiota; Bacteria
PubMed: 37054512
DOI: 10.1016/j.mib.2023.102306 -
Trends in Microbiology Dec 2023Acinetobacter baumannii is a Gram-negative opportunistic bacterium responsible for nosocomial and community-acquired infections. This pathogen is globally disseminated... (Review)
Review
Acinetobacter baumannii is a Gram-negative opportunistic bacterium responsible for nosocomial and community-acquired infections. This pathogen is globally disseminated and associated with high levels of antibiotic resistance, which makes it an important threat to human health. Recently, new evidence showed that several A. baumannii isolates can survive and proliferate within eukaryotic professional and/or nonprofessional phagocytic cells, with in vivo consequences. This review provides updated information and describes the tools that A. baumannii possesses to adhere, colonize, and replicate in host cells. Additionally, we emphasize the high genetic and phenotypic heterogeneity detected amongst A. baumannii isolates and its impact on the bacterial intracellular features. We also discuss the need for standardized methods to characterize this pathogen robustly and consequently consider some strains as facultative intracellular bacteria.
Topics: Humans; Drug Resistance, Multiple, Bacterial; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Microbial Sensitivity Tests
PubMed: 37487768
DOI: 10.1016/j.tim.2023.06.007 -
Cell Reports Methods Dec 2023We created a generalizable pipeline for antibiotic-resistance-gene-free plasmid (ARGFP)-based cloning using a dual auxotrophic- and essential-gene-based selection...
We created a generalizable pipeline for antibiotic-resistance-gene-free plasmid (ARGFP)-based cloning using a dual auxotrophic- and essential-gene-based selection strategy. We use auxotrophic selection to construct plasmids in engineered E. coli DH10B cloning strains and both auxotrophic- and essential-gene-based selection to (1) select for recombinant strains and (2) maintain a plasmid in E. coli Nissle 1917, a common chassis for engineered probiotic applications, and E. coli MG1655, the laboratory "wild-type" E. coli strain. We show that our approach has comparable efficiency to that of antibiotic-resistance-gene-based cloning. We also show that the double-knockout Nissle and MG1655 strains are simple to transform with plasmids of interest. Notably, we show that the engineered Nissle strains are amenable to long-term plasmid maintenance in repeated culturing as well as in the mouse gut, demonstrating the potential for broad applications while minimizing the risk of antibiotic resistance spread via horizontal gene transfer.
Topics: Animals; Mice; Anti-Bacterial Agents; Escherichia coli; Plasmids; Drug Resistance, Microbial; Cloning, Molecular
PubMed: 38086386
DOI: 10.1016/j.crmeth.2023.100669 -
Microbiome Jul 2023The resistome, the collection of antibiotic resistance genes (ARGs) in a microbiome, is increasingly recognised as relevant to the development of clinically relevant...
BACKGROUND
The resistome, the collection of antibiotic resistance genes (ARGs) in a microbiome, is increasingly recognised as relevant to the development of clinically relevant antibiotic resistance. Many metagenomic studies have reported resistome differences between groups, often in connection with disease and/or antibiotic treatment. However, the consistency of resistome associations with antibiotic- and non-antibiotic-treated diseases has not been established. In this study, we re-analysed human gut microbiome data from 26 case-control studies to assess the link between disease and the resistome.
RESULTS
The human gut resistome is highly variable between individuals both within and between studies, but may also vary significantly between case and control groups even in the absence of large taxonomic differences. We found that for diseases commonly treated with antibiotics, namely cystic fibrosis and diarrhoea, patient microbiomes had significantly elevated ARG abundances compared to controls. Disease-associated resistome expansion was found even when ARG abundance was high in controls, suggesting ongoing and additive ARG acquisition in disease-associated strains. We also found a trend for increased ARG abundance in cases from some studies on diseases that are not treated with antibiotics, such as colorectal cancer.
CONCLUSIONS
Diseases commonly treated with antibiotics are associated with expanded gut resistomes, suggesting that historical exposure to antibiotics has exerted considerable selective pressure for ARG acquisition in disease-associated strains. Video Abstract.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Anti-Bacterial Agents; Drug Resistance, Microbial; Genes, Bacterial
PubMed: 37507809
DOI: 10.1186/s40168-023-01610-1 -
Revista Espanola de Quimioterapia :... Nov 2023Pseudomonas aeruginosa is a pathogen that has a high propensity to develop antibiotic resistance, and the emergence of multidrug-resistant strains is a major concern for... (Review)
Review
Pseudomonas aeruginosa is a pathogen that has a high propensity to develop antibiotic resistance, and the emergence of multidrug-resistant strains is a major concern for global health. The mortality rate associated with infections caused by this microorganism is significant, especially those caused by multidrug-resistant strains. The antibiotics used to treat these infections include quinolones, aminoglycosides, colistin, and β-lactams. However, novel combinations of β-lactams-β-lactamase inhibitors and cefiderocol offer advantages over other members of their family due to their better activity against certain resistance mechanisms. Selecting the appropriate empiric antibiotic treatment requires consideration of the patient's clinical entity, comorbidities, and risk factors for multidrug-resistant pathogen infections, and local epidemiological data. Optimizing antibiotic pharmacokinetics, controlling the source of infection, and appropriate collection of samples are crucial for successful treatment. In the future, the development of alternative treatments and strategies, such as antimicrobial peptides, new antibiotics, phage therapy, vaccines, and colonization control, holds great promise for the management of P. aeruginosa infections.
Topics: Humans; Pseudomonas aeruginosa; Anti-Bacterial Agents; Colistin; beta-Lactams; beta-Lactamase Inhibitors; Pseudomonas Infections; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests
PubMed: 37997873
DOI: 10.37201/req/s01.13.2023 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Anti-Bacterial Agents; Gastritis; Drug Resistance, Microbial
PubMed: 37850053
DOI: 10.3389/fcimb.2023.1296784 -
Current Opinion in Microbiology Oct 2023Antibiotic-resistant microbe-mediated deaths are a major worldwide health issue. Unfortunately, due to microbial adaptation to develop resistance, some antibiotics are... (Review)
Review
Antibiotic-resistant microbe-mediated deaths are a major worldwide health issue. Unfortunately, due to microbial adaptation to develop resistance, some antibiotics are nullified early in their usage, and worse, resistance is detected before they can even be prescribed. Copper's toxicity since antiquity against microbes at the host-pathogen interface offers a fascinating weapon to fight antimicrobial resistance. Here, we briefly review why copper is so effective, how drugs that work with copper are effective antimicrobials, and how compounds such as these could reinvigorate investment in antimicrobial development.
Topics: Copper; Ionophores; Drug Resistance, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents
PubMed: 37406562
DOI: 10.1016/j.mib.2023.102355 -
Conjugative transfer of streptococcal prophages harboring antibiotic resistance and virulence genes.The ISME Journal Sep 2023Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting...
Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting antimicrobial resistance genes (ARGs). Herein we characterize a prevalent family of prophages in Streptococcus, designated SMphages, which harbor twenty-five ARGs that collectively confer resistance to ten antimicrobial classes, including vanG-type vancomycin resistance locus and oxazolidinone resistance gene optrA. SMphages integrate into four chromosome attachment sites by utilizing three types of integration modules and undergo excision in response to phage induction. Moreover, we characterize four subtypes of Alp-related surface proteins within SMphages, the lethal effects of which are extensively validated in cell and animal models. SMphages transfer via high-frequency conjugation that is facilitated by integrative and conjugative elements from either donors or recipients. Our findings explain the widespread of SMphages and the rapid dissemination of ARGs observed in members of the Streptococcus genus.
Topics: Animals; Prophages; Virulence; Streptococcus; Anti-Infective Agents; Drug Resistance, Microbial; Anti-Bacterial Agents; Gene Transfer, Horizontal; Plasmids; Conjugation, Genetic
PubMed: 37369704
DOI: 10.1038/s41396-023-01463-4