Comparative Genomic Analysis of Rapid Evolution of an Extreme-Drug-Resistant Acinetobacter baumannii Clone

Tan, Sean Yang-Yi; Chua, Song Lin; Yang, Liu; Høiby, Niels; Andersen, Leif Percival; Givskov, Michael; Song, Zhijun; Yang, Liang

doi:10.1093/gbe/evt047

Cited by 37 publications

(32 citation statements)

References 42 publications

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“…Genomic sequencing revealed comprehensive drug-resistance mechanisms, such as a 41.6-kb closely related antibiotic resistance island in the chromosome (Huang et al, 2012), the horizontally transmittable carbapenem resistance gene (bla ) containing a plasmid (in isolate MDR-TJ, with 454 Titanium) among different A. baumannii strains (Huang et al, 2012;Lee et al, 2013), a list of antimicrobial resistance-associated genes (with 454 and SOLiD) (Rolain et al, 2013), a diversified resistance gene list (with Illumina Hiseq2000) (Tan et al, 2013), and longitudinally evolved antibiotic resistance gene mutations and mutational pathways under pressure from the antibiotic colistin (with 454 Titanium) (Snitkin et al, 2013). Since its invention by Rothberg et al (2011), Ion Torrent sequencing technology has been successfully applied to complete genomic sequencing, such as in Clostridium sp.…”

Section: Whole Genome Sequencing Is a Feasible Way To Investigate Thementioning

confidence: 99%

Antibiotic resistance mechanisms of Myroides sp.

Yuan

et al. 2016

J. Zhejiang Univ. Sci. B

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Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.

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Section: Whole Genome Sequencing Is a Feasible Way To Investigate Thementioning

confidence: 99%

Antibiotic resistance mechanisms of Myroides sp.

Yuan

et al. 2016

J. Zhejiang Univ. Sci. B

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“…Whole-genome sequences for representative A. baumannii strains from each of the three major IC lineages (65) were downloaded from the NCBI database and also included in some phylogenetic analyses.…”

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confidence: 99%

Utility of Whole-Genome Sequencing in Characterizing Acinetobacter Epidemiology and Analyzing Hospital Outbreaks

2016

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bAcinetobacter baumannii frequently causes nosocomial infections and outbreaks. Whole-genome sequencing (WGS) is a promising technique for strain typing and outbreak investigations. We compared the performance of conventional methods with WGS for strain typing clinical Acinetobacter isolates and analyzing a carbapenem-resistant A. baumannii (CRAB) outbreak. We performed two band-based typing techniques (pulsed-field gel electrophoresis and repetitive extragenic palindromic-PCR), multilocus sequence type (MLST) analysis, and WGS on 148 Acinetobacter calcoaceticus-A. baumannii complex bloodstream isolates collected from a single hospital from 2005 to 2012. Phylogenetic trees inferred from core-genome single nucleotide polymorphisms (SNPs) confirmed three Acinetobacter species within this collection. Four major A. baumannii clonal lineages (as defined by MLST) circulated during the study, three of which are globally distributed and one of which is novel. WGS indicated that a threshold of 2,500 core SNPs accurately distinguished A. baumannii isolates from different clonal lineages. The bandbased techniques performed poorly in assigning isolates to clonal lineages and exhibited little agreement with sequence-based techniques. After applying WGS to a CRAB outbreak that occurred during the study, we identified a threshold of 2.5 core SNPs that distinguished nonoutbreak from outbreak strains. WGS was more discriminatory than the band-based techniques and was used to construct a more accurate transmission map that resolved many of the plausible transmission routes suggested by epidemiologic links. Our study demonstrates that WGS is superior to conventional techniques for A. baumannii strain typing and outbreak analysis. These findings support the incorporation of WGS into health care infection prevention efforts.A n important role of clinical microbiology is to identify relationships between bacterial isolates. At a broad level, phenotypic and genotypic tests are used to categorize bacterial isolates into the same or different species. Within a bacterial species, techniques are used to group isolates into clonal lineages, which are groups of closely related bacteria that share a recent common ancestor but have spread regionally or globally. At a more local level, infection control practitioners must determine whether a group of isolates constitutes a hospital outbreak by ascertaining whether the isolates have a degree of similarity consistent with a common source within the hospital. Once isolates belonging to a hospital outbreak have been identified, similarities and differences between these isolates can be exploited to generate a transmission map to aid in finding the source of the outbreak and in disrupting ongoing pathways of transmission. For some groups of bacteria, such as Acinetobacter, discernment at each level has medically important consequences and therefore must be accomplished by hospital-associated clinical microbiology laboratories.Within the Acinetobacter genus, the Acinetobacter calcoaceticusAcinetobac...

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“…An increasing number of A. baumannii infections in patients have been detected among U.S. military service members injured in Iraq and Afghanistan (5). The genetic adaptability of A. baumannii allows it to gain resistance to a wide spectrum of commercial antibiotics, and the intrinsic presence of various efflux pumps in A. baumannii also contributes to an insensitivity to many antibiotics (6)(7)(8), resulting in very few viable treatment options for Acinetobacter infections (9)(10)(11). In addition, most of the clinical strains of A. baumannii also harbor a large antimicrobial resistance island (RI) of 86 kb that contains several beta-lactamase genes, conferring resistance to beta-lactam antibiotics (12,13).…”

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confidence: 99%

Insect-Derived Cecropins Display Activity against Acinetobacter baumannii in a Whole-Animal High-Throughput Caenorhabditis elegans Model

Jayamani

Rajaraman

Larkins-Ford

et al. 2015

Antimicrob Agents Chemother

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The rise of multidrug-resistant Acinetobacter baumannii and a concomitant decrease in antibiotic treatment options warrants a search for new classes of antibacterial agents. We have found that A. baumannii is pathogenic and lethal to the model host organism Caenorhabditis elegans and have exploited this phenomenon to develop an automated, high-throughput, high-content screening assay in liquid culture that can be used to identify novel antibiotics effective against A. baumannii. The screening assay involves coincubating C. elegans with A. baumannii in 384-well plates containing potential antibacterial compounds. At the end of the incubation period, worms are stained with a dye that stains only dead animals, and images are acquired using automated microscopy and then analyzed using an automated image analysis program. This robust assay yields a Z= factor consistently greater than 0.7. In a pilot experiment to test the efficacy of the assay, we screened a small custom library of synthetic antimicrobial peptides (AMPs) that were synthesized using publicly available sequence data and/or transcriptomic data from immune-challenged insects. We identified cecropin A and 14 other cecropin or cecropin-like peptides that were able to enhance C. elegans survival in the presence of A. baumannii. Interestingly, one particular hit, BR003-cecropin A, a cationic peptide synthesized by the mosquito Aedes aegypti, showed antibiotic activity against a panel of Gram-negative bacteria and exhibited a low MIC (5 g/ml) against A. baumannii. BR003-cecropin A causes membrane permeability in A. baumannii, which could be the underlying mechanism of its lethality.A cinetobacter baumannii is a Gram-negative, opportunistic bacterium that has recently emerged as a dangerous nosocomial pathogen (1-4). An increasing number of A. baumannii infections in patients have been detected among U.S. military service members injured in Iraq and Afghanistan (5). The genetic adaptability of A. baumannii allows it to gain resistance to a wide spectrum of commercial antibiotics, and the intrinsic presence of various efflux pumps in A. baumannii also contributes to an insensitivity to many antibiotics (6-8), resulting in very few viable treatment options for Acinetobacter infections (9-11). In addition, most of the clinical strains of A. baumannii also harbor a large antimicrobial resistance island (RI) of 86 kb that contains several beta-lactamase genes, conferring resistance to beta-lactam antibiotics (12, 13). The scarcity of antibiotics that can be used against A. baumannii infections drives the need for new kinds of antimicrobial agents (14).Empirical drug screening methods traditionally involve in vitro assays to measure the MICs for various pathogens. This is followed by in vivo testing of the drugs to measure their toxicity to eukaryotic cells (15). The disadvantage of these traditional assays is that a significant number of hit compounds show nonspecific toxicity to eukaryotic cells and are not promising as therapeutics (16). In this paper, we describ...

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Comparative Genomic Analysis of Rapid Evolution of an Extreme-Drug-Resistant Acinetobacter baumannii Clone

Cited by 37 publications

References 42 publications

Antibiotic resistance mechanisms of Myroides sp.

Antibiotic resistance mechanisms of Myroides sp.

Utility of Whole-Genome Sequencing in Characterizing Acinetobacter Epidemiology and Analyzing Hospital Outbreaks

Insect-Derived Cecropins Display Activity against Acinetobacter baumannii in a Whole-Animal High-Throughput Caenorhabditis elegans Model

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