Antimicrobial resistance in enteric bacteria: current state and next-generation solutions

Antimicrobial resistance (AMR) is one of the greatest public health challenges we are currently facing. To develop effective interventions against this, it is essential to understand the processes behind the spread of AMR. These are partly dependent on the dynamics of horizontal transfer of resistance genes between bacteria, which can occur by conjugation (direct contact), transformation (uptake from the environment) or transduction (mediated by bacteriophages). Mathematical modelling is a powerful tool to investigate the dynamics of AMR, however its application to study the horizontal transfer of AMR genes is currently unclear. In this systematic review, we searched for mathematical modelling studies which focused on horizontal transfer of AMR genes. We compared their aims and methods using a list of predetermined criteria, and utilized our results to assess the current state of this research field. Of the 43 studies we identified, most focused on the transfer of single genes by conjugation in Escherichia coli in culture, and its impact on the bacterial evolutionary dynamics. Our findings highlight the existence of an important research gap on the dynamics of transformation and transduction, and the overall public health implications of horizontal transfer of AMR genes. To further develop this field and improve our ability to control AMR, it is essential that we clarify the structural complexity required to study the dynamics of horizontal gene transfer, which will require cooperation between microbiologists and modellers.

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The characterization of ESBL genes in Escherichia coli and Klebsiella pneumoniae causing nosocomial infections in Vietnam

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2938 ◽

2013 ◽

Vol 7 (12) ◽

pp. 922-928 ◽

Cited By ~ 15

Author(s):

Nguyen Hoang Thu Trang ◽

Tran Vu Thieu Nga ◽

James I Campbell ◽

Nguyen Trong Hiep ◽

Jeremy Farrar ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Klebsiella Pneumoniae ◽

Nosocomial Infections ◽

Enteric Bacteria ◽

E Coli ◽

Plasmid Analysis ◽

Resistance Plasmids ◽

Genes Encoding ◽

Third Generation Cephalosporins

Background: Extended-spectrum β-lactamases (ESBLs) are enzymes capable of hydrolyzing oxyimino-β-lactams and inducing resistance to third generation cephalosporins. The genes encoding ESBLs are widespread and generally located on highly transmissible resistance plasmids. We aimed to investigate the complement of ESBL genes in E. coli and Klebsiella pneumoniae causing nosocomial infections in hospitals in Ho Chi Minh City, Vietnam. Methodology: Thirty-two non-duplicate isolates of E. coli and Klebsiella pneumoniae causing nosocomial infections, isolated between March and June 2010, were subjected to antimicrobial susceptibility testing. All isolates were PCR-amplified to detect the blaSHV, blaTEM and blaCTX-M ESBL genes and subjected to plasmid analysis. Results: We found that co-resistance to multiple antimicrobials was highly prevalent, and we report the predominance of the blaCTX-M-15 and blaCTX-M-27 genes, located on highly transmissible plasmids ranging from 50 to 170 kb in size. Conclusions: Our study represents a snap shot of ESBL-producing enteric bacteria causing nosocomial infections in this setting. We suggest that antimicrobial resistance in nosocomial E. coli and Klebsiella pneumoniae is rampant in Vietnam and ESBL organisms are widespread. In view of these data and the dramatic levels of antimicrobial resistance reported in Vietnam we advocate an urgent review of antimicrobial use in the Vietnamese healthcare system.

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Metagenomics: aid to combat antimicrobial resistance in diarrhea

Gut Pathogens ◽

10.1186/s13099-019-0331-8 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 5

Author(s):

Rituparna De

Keyword(s):

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Genetic Recombination ◽

Molecular Taxonomy ◽

Ecological Niches ◽

Next Generation ◽

Genetic Determinants ◽

Antimicrobial Resistance Genes ◽

And Function ◽

Generation Sequencing

Abstract Antimicrobial resistance (AMR) has emerged as an obstacle in the supple administration of antimicrobial agents to critical diarrheal patients. Most diarrheal pathogens have developed resistance against the major classes of antibiotics commonly used for assuaging diarrheal symptoms. Antimicrobial resistance develops when pathogens acquire antimicrobial resistance genes (ARGs) through genetic recombination from commensals and pathogens. These are the constituents of the complex microbiota in all ecological niches. The recombination events may occur in the environment or in the gut. Containment of AMR can be achieved through a complete understanding of the complex and diverse structure and function of the microbiota. Its taxonomic entities serve as focal points for the dissemination of antimicrobial resistance genetic determinants. Molecular methods complemented with culture-based diagnostics have been historically implemented to document these natural events. However, the advent of next-generation sequencing has revolutionized the field of molecular epidemiology. It has revolutionized the method of addressing relevant problems like diagnosis and surveillance of infectious diseases and the issue of antimicrobial resistance. Metagenomics is one such next-generation technique that has proved to be a monumental advancement in the area of molecular taxonomy. Current understanding of structure, function and dysbiosis of microbiota associated with antimicrobial resistance was realized due to its conception. This review describes the major milestones achieved due to the advent and implementation of this new technique in the context of antimicrobial resistance. These achievements span a wide panorama from the discovery of novel microorganisms to invention of translational value.

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Enteric Microbiota–Gut–Brain Axis from the Perspective of Nuclear Receptors

International Journal of Molecular Sciences ◽

10.3390/ijms19082210 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2210 ◽

Cited By ~ 7

Author(s):

Kalina Duszka ◽

Walter Wahli

Keyword(s):

Gut Microbiota ◽

Complex Systems ◽

Nuclear Receptors ◽

Enteric Bacteria ◽

Full Potential ◽

Gut Flora ◽

Current State ◽

The Brain

Nuclear receptors (NRs) play a key role in regulating virtually all body functions, thus maintaining a healthy operating body with all its complex systems. Recently, gut microbiota emerged as major factor contributing to the health of the whole organism. Enteric bacteria have multiple ways to influence their host and several of them involve communication with the brain. Mounting evidence of cooperation between gut flora and NRs is already available. However, the full potential of the microbiota interconnection with NRs remains to be uncovered. Herewith, we present the current state of knowledge on the multifaceted roles of NRs in the enteric microbiota–gut–brain axis.

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The evolution of the cancer stem cell state in glioblastoma: emerging insights into the next generation of functional interactions

Neuro-Oncology ◽

10.1093/neuonc/noaa259 ◽

2020 ◽

Author(s):

Kelly Mitchell ◽

Katie Troike ◽

Daniel J Silver ◽

Justin D Lathia

Keyword(s):

Cellular Heterogeneity ◽

Next Generation ◽

Cell State ◽

Functional Interactions ◽

Current State ◽

Key Concepts ◽

Discrete Population ◽

A Cell ◽

Stem Cell State ◽

Primary Malignant Brain Tumor

Abstract Cellular heterogeneity is a hallmark of advanced cancers and has been ascribed in part to a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). Glioblastoma (GBM), the most common primary malignant brain tumor, has served as a platform for the study of CSCs. In addition to illustrating the complexities of CSC biology, these investigations have led to a deeper understanding of GBM pathogenesis, revealed novel therapeutic targets, and driven innovation towards the development of next-generation therapies. While there continues to be an expansion in our knowledge of how CSCs contribute to GBM progression, opportunities have emerged to revisit this conceptual framework. In this review, we will summarize the current state of CSCs in GBM using key concepts of evolution as a paradigm (variation, inheritance, selection, and time) to describe how the CSC state is subject to alterations of cell intrinsic and extrinsic interactions that shape their evolutionarily trajectory. We identify emerging areas for future consideration, including appreciating CSCs as a cell state that is subject to plasticity, as opposed to a discrete population. These future considerations will not only have an impact on our understanding of this ever-expanding field but will also provide an opportunity to inform future therapies to effectively treat this complex and devastating disease.

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New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides

Journal of Clinical Microbiology ◽

10.1128/jcm.03395-15 ◽

2016 ◽

Vol 54 (9) ◽

pp. 2225-2232 ◽

Cited By ~ 23

Author(s):

Matthew P. Crotty ◽

Tamara Krekel ◽

Carey-Ann D. Burnham ◽

David J. Ritchie

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Resistance ◽

Next Generation ◽

Gram Positive ◽

Content Type ◽

Skin Structure ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant ◽

The U.S

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibitin vitroactivity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstratein vitroactivity against VRE. These new Gram-positive agents are reviewed here.

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Translating Lung Microbiome Profiles into the Next-Generation Diagnostic Gold Standard for Pneumonia: a Clinical Investigator’s Perspective

mSystems ◽

10.1128/msystems.00153-17 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 6

Author(s):

Georgios D. Kitsios

Keyword(s):

Pulmonary Infections ◽

Next Generation ◽

Clinical Validity ◽

Lung Microbiome ◽

Current State ◽

Incubation Periods ◽

Culture Independent ◽

Diagnostic Approaches ◽

Microbial Dna ◽

Generation Sequencing

ABSTRACT Severe bacterial pneumonia is a major global cause of morbidity and mortality, yet current diagnostic approaches rely on identification of causative pathogens by cultures, which require extended incubation periods and often fail to detect relevant pathogens. Consequently, patients are prescribed broad-spectrum antibiotics in a “one-size-fits-all” manner, which may be inappropriate for their individual needs and promote antibiotic resistance. My research focuses on leveraging next-generation sequencing of microbial DNA directly from patient samples for the development of new, culture-independent definitions of pneumonia. In this perspective article, I discuss the current state of the field and focus on the conceptual and research design challenges for clinical translation. With ongoing technological advancements and application of computational biology methods for assessing clinical validity and utility, I anticipate that sequencing-based diagnostics will soon be able to positively disrupt the way we think about, diagnose, and treat pulmonary infections.

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