scholarly journals Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family

2021 ◽  
Author(s):  
Peter J. Stogios ◽  
Emily Bordeleau ◽  
Zhiyu Xu ◽  
Tatiana Skarina ◽  
Elena Evdokimova ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Pathogenic Bacteria ◽  
Antibiotic Resistance Genes ◽  
Crystallographic Analysis ◽  
Clinical Isolates ◽  
Critical Data ◽  
Broad Spectrum Resistance ◽  
The Family ◽  
Environmental Bacteria ◽  
High Level

ABSTRACTThe environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an AAC(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment.

scholarly journals ANÁLISE COMPARATIVA DOS FATORES DE VIRULÊNCIA DOS ISOLADOS CLÍNICOS E AMBIENTAIS DE PSEUDOMONAS AERUGINOSA

2019 ◽  
Vol 11 (3) ◽  
pp. 41-50
Author(s):  
Isabela Alves de Souza ◽  
Doroti de Oliveira Garcia ◽  
Laís Anversa ◽  
Renata Katsuko Takayama Kobayashi ◽  
Gerson Nakazato ◽  
...  
Keyword(s):  
Public Health ◽  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Clinical Isolates ◽  
Environmental Isolates ◽  
High Level

Pseudomonas aeruginosais a very important bacteria for public health because it is present in the environment and clinical infections. The aim of this study was toevaluate the virulence factors such as motility, protease and rhamnolipids in clinical and environmental P. aeruginosaisolates.Twenty-five clinical isolates and ten environmental isolates were analyzed by phenotypic assays and categorized into non-mobile, weakly, moderately and highly mobile strains; and producers of protease and rhamnolipids. The isolates were tested in triplicate on three different days. Environmental isolates produced virulence factors such as motility (Swimming and Twitching), and Ramnolipids significantly higher than clinical isolates.This study alerts us to the high level of pathogenicity of P. aeruginosastrains, mainly environmental strains. For a better understanding of motility and rhamnolipids, virulence factors that are directly associated with the biofilms formation, may favor studies that complement the research aimed at the control of pathogenic bacteria.

Assessing the heterogeneity of in silico plasmid predictions based on whole-genome-sequenced clinical isolates

2017 ◽  
Vol 20 (3) ◽  
pp. 857-865 ◽  
Author(s):  
Cedric C Laczny ◽  
Valentina Galata ◽  
Achim Plum ◽  
Andreas E Posch ◽  
Andreas Keller
Keyword(s):  
Antibiotic Resistance ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Antibiotic Resistance Genes ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Chromosomal Dna ◽  
Accurate Identification ◽  
Resistance Factors ◽  
The Individual

AbstractHigh-throughput next-generation shotgun sequencing of pathogenic bacteria is growing in clinical relevance, especially for chromosomal DNA-based taxonomic identification and for antibiotic resistance prediction. Genetic exchange is facilitated for extrachromosomal DNA, e.g. plasmid-borne antibiotic resistance genes. Consequently, accurate identification of plasmids from whole-genome sequencing (WGS) data remains one of the major challenges for sequencing-based precision medicine in infectious diseases. Here, we assess the heterogeneity of four state-of-the-art tools (cBar, PlasmidFinder, plasmidSPAdes and Recycler) for the in silico prediction of plasmid-derived sequences from WGS data. Heterogeneity, sensitivity and precision were evaluated by reference-independent and reference-dependent benchmarking using 846 Gram-negative clinical isolates. Interestingly, the majority of predicted sequences were tool-specific, resulting in a pronounced heterogeneity across tools for the reference-independent assessment. In the reference-dependent assessment, sensitivity and precision values were found to substantially vary between tools and across taxa, with cBar exhibiting the highest median sensitivity (87.45%) but a low median precision (27.05%). Furthermore, integrating the individual tools into an ensemble approach showed increased sensitivity (95.55%) while reducing the precision (25.62%). CBar and plasmidSPAdes exhibited the strongest concordance with respect to identified antibiotic resistance factors. Moreover, false-positive plasmid predictions typically contained only few antibiotic resistance factors. In conclusion, while high degrees of heterogeneity and variation in sensitivity and precision were observed across the different tools and taxa, existing tools are valuable for investigating the plasmid-borne resistome. Nevertheless, additional studies on representative clinical data sets will be necessary to translate in silico plasmid prediction approaches from research to clinical application.

scholarly journals The Bacterial Genomic Context of Highly Trimethoprim-Resistant DfrB Dihydrofolate Reductases Highlights an Emerging Threat to Public Health

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 433
Author(s):  
Claudèle Lemay-St-Denis ◽  
Sarah-Slim Diwan ◽  
Joelle N. Pelletier
Keyword(s):  
Public Health ◽  
Pathogenic Bacteria ◽  
Antibiotic Resistance Genes ◽  
Genomic Context ◽  
Bacterial Genomes ◽  
New Members ◽  
The Family ◽  
Dihydrofolate Reductases ◽  
Systematic Biases ◽  
The 1960S

Type B dihydrofolate reductase (dfrb) genes were identified following the introduction of trimethoprim in the 1960s. Although they intrinsically confer resistance to trimethoprim (TMP) that is orders of magnitude greater than through other mechanisms, the distribution and prevalence of these short (237 bp) genes is unknown. Indeed, this knowledge has been hampered by systematic biases in search methodologies. Here, we investigate the genomic context of dfrbs to gain information on their current distribution in bacterial genomes. Upon searching publicly available databases, we identified 61 sequences containing dfrbs within an analyzable genomic context. The majority (70%) of those sequences also harbor virulence genes and 97% of the dfrbs are found near a mobile genetic element, representing a potential risk for antibiotic resistance genes. We further identified and confirmed the TMP-resistant phenotype of two new members of the family, dfrb10 and dfrb11. Dfrbs are found both in Betaproteobacteria and Gammaproteobacteria, a majority (59%) being in Pseudomonas aeruginosa. Previously labelled as strictly plasmid-borne, we found 69% of dfrbs in the chromosome of pathogenic bacteria. Our results demonstrate that the intrinsically TMP-resistant dfrbs are a potential emerging threat to public health and justify closer surveillance of these genes.

A Review on Quantum Dots: Synthesis to In- silico Analysis as Next Generation Antibacterial Agents

2019 ◽  
Vol 20 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Sounik Manna ◽  
Munmun Ghosh ◽  
Ranadhir Chakraborty ◽  
Sudipto Ghosh ◽  
Santi M. Mandal
Keyword(s):  
Quantum Dots ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Antimicrobial Properties ◽  
Binding Potential ◽  
Antibacterial Drug ◽  
Next Generation ◽  
Mechanism Of Reaction ◽  
High Level ◽  
Membrane Components

Succumbing to Multi-Drug Resistant (MDR) bacteria is a great distress to the recent health care system. Out of the several attempts that have been made to kill MDR pathogens, a few gained short-lived success. The failures, of the discovered or innovated antimicrobials, were mostly due to their high level of toxicity to hosts and the phenomenal rate of developing resistance by the pathogens against the new arsenal. Recently, a few quantum dots were tested against the pathogenic bacteria and therefore, justified for potential stockpiling of next-generation antibacterial agents. The key players for antimicrobial properties of quantum dots are considered to be Reactive Oxygen Species (ROS). The mechanism of reaction between bacteria and quantum dots needs to be better understood. They are generally targeted towards the cell wall and membrane components as lipoteichoic acid and phosphatidyl glycerol of bacteria have been documented here. In this paper, we have attempted to simulate ZnS quantum dots and have analysed their mechanism of reaction as well as binding potential to the above bacterial membrane components using CDOCKER. Results have shown a high level of antibacterial activity towards several pathogenic bacteria which specify their potentiality for future generation antibacterial drug development.

scholarly journals Molecular basis of macrolide-lincosamide-streptogramin (MLS) resistance in Finegoldia magna clinical isolates

Anaerobe ◽  
2020 ◽  
Vol 64 ◽  
pp. 102220
Author(s):  
François Guérin ◽  
Sabrine Lachaal ◽  
Michel Auzou ◽  
Cécile Le Brun ◽  
Olivier Barraud ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Clinical Isolates

scholarly journals Extracellular DNA (eDNA): Neglected and Potential Sources of Antibiotic Resistant Genes (ARGs) in the Aquatic Environments

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 874
Author(s):  
Periyasamy Sivalingam ◽  
John Poté ◽  
Kandasamy Prabakar
Keyword(s):  
Antibiotic Resistance ◽  
Health Risk ◽  
Genetic Material ◽  
Antibiotic Resistance Genes ◽  
Extracellular Dna ◽  
Antibiotic Resistant ◽  
Treatment Technologies ◽  
Environmental Bacteria ◽  
Global Threat ◽  
Potential Public Health

Over the past decades, the rising antibiotic resistance bacteria (ARB) are continuing to emerge as a global threat due to potential public health risk. Rapidly evolving antibiotic resistance and its persistence in the environment, have underpinned the need for more studies to identify the possible sources and limit the spread. In this context, not commonly studied and a neglected genetic material called extracellular DNA (eDNA) is gaining increased attention as it can be one of the significant drivers for transmission of extracellular ARGS (eARGs) via horizontal gene transfer (HGT) to competent environmental bacteria and diverse sources of antibiotic-resistance genes (ARGs) in the environment. Consequently, this review highlights the studies that address the environmental occurrence of eDNA and encoding eARGs and its impact on the environmental resistome. In this review, we also brief the recent dedicated technological advancements that are accelerating extraction of eDNA and the efficiency of treatment technologies in reducing eDNA that focuses on environmental antibiotic resistance and potential ecological health risk.

scholarly journals Association between 16S rRNA gene mutations and susceptibility to amikacin in Mycobacterium avium Complex and Mycobacterium abscessus clinical isolates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su-Young Kim ◽  
Dae Hun Kim ◽  
Seong Mi Moon ◽  
Ju Yeun Song ◽  
Hee Jae Huh ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Mycobacterium Avium ◽  
Inhibitory Concentration ◽  
Gene Mutations ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Rrna Gene ◽  
High Level ◽  
Culture Conversion

AbstractWe evaluated the association between 16S rRNA gene (rrs) mutations and susceptibility in clinical isolates of amikacin-resistant nontuberculous mycobacteria (NTM) in NTM-pulmonary disease (PD) patients. Susceptibility was retested for 134 amikacin-resistant isolates (minimum inhibitory concentration [MIC] ≥ 64 µg/ml) from 86 patients. Amikacin resistance was reconfirmed in 102 NTM isolates from 62 patients with either Mycobacterium avium complex-PD (MAC-PD) (n = 54) or M. abscessus-PD (n = 8). MICs and rrs mutations were evaluated for 318 single colonies from these isolates. For the 54 MAC-PD patients, rrs mutations were present in 34 isolates (63%), comprising all 31 isolates with amikacin MICs ≥ 128 µg/ml, but only three of 23 isolates with an MIC = 64 µg/ml. For the eight M. abscessus-PD patients, all amikacin-resistant (MIC ≥ 64 µg/ml) isolates had rrs mutations. In amikacin-resistant isolates, the A1408G mutation (n = 29) was most common. Two novel mutations, C1496T and T1498A, were also identified. The culture conversion rate did not differ by amikacin MIC. Overall, all high-level and 13% (3/23) of low-level amikacin-resistant MAC isolates had rrs mutations whereas mutations were present in all amikacin-resistant M. abscessus isolates. These findings are valuable for managing MAC- and M. abscessus-PD and suggest the importance of phenotypic and genotypic susceptibility testing.

scholarly journals Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 378
Author(s):  
Inka Marie Willms ◽  
Maja Grote ◽  
Melissa Kocatürk ◽  
Lukas Singhoff ◽  
Alina Andrea Kraft ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Reference Database ◽  
Functional Metagenomics ◽  
Beta Lactam ◽  
Public Attention ◽  
Soil Ecosystems ◽  
High Level ◽  
Antibiotic Efflux

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.

scholarly journals Implementation of the Family HELP Protocol: A Feasibility Project for a West Texas ICU

Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 146
Author(s):  
Rebecca McClay
Keyword(s):  
Strong Support ◽  
Family Intervention ◽  
Successful Implementation ◽  
Positive Perception ◽  
Family Presence ◽  
West Texas ◽  
The Family ◽  
Control And Prevention ◽  
High Level ◽  
Near Future

The purpose of this project was to determine if bedside intensive care unit (ICU) nurse buy-in to the Family Hospital Elder Life Program (HELP) protocol was sufficient to make implementation feasible at one county hospital in West Texas. Surveys were anonymous with ballot box collection being available to the bedside ICU nurses for one week each. Questions were based on literature findings of expected outcomes, identified barriers and facilitators, Calgary Family Intervention Method framework domains, and the Centers for Disease Control and Prevention Framework for program evaluation. Outcome measures were taken from the stated aims of the project and evaluated from paired baseline and summative survey questions. Survey participation was approximately half of nurses employed in the studied ICU. Analysis of the surveys showed a positive perception of family presence decreasing patient delirium symptoms, and a positive perception of the Family HELP protocol. The results described a high perception of family members as partners in care and high intention to implement the Family HELP protocol, indicating strong support of a full implementation of the protocol. The high level of bedside nurse buy-in present in this study has large implications for successful implementation of the Family HELP protocol in the near future, with sustainability and continued use supported by potential inclusion of the task in the electronic health record charting.

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