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Asset Tag: Infectious disease

July 7, 2019  |  

Complete genome sequences of four Salmonella enterica subsp. enterica serovar Senftenberg and Montevideo isolates associated with a 2016 multistate outbreak in the United States.

A multistate outbreak of 11 Salmonella infections linked to pistachio nuts occurred in 2016. In this announcement, we report the complete genome sequences of four Salmonella enterica subsp. enterica serovar Senftenberg and S. enterica subsp. enterica serovar Montevideo isolates from pistachios collected during the 2016 outbreak investigation.

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July 7, 2019  |  

Genomic sequencing of Bordetella pertussis for epidemiology and global surveillance of whooping cough.

Bordetella pertussis causes whooping cough, a highly contagious respiratory disease that is reemerging in many world regions. The spread of antigen-deficient strains may threaten acellular vaccine efficacy. Dynamics of strain transmission are poorly defined because of shortcomings in current strain genotyping methods. Our objective was to develop a whole-genome genotyping strategy with sufficient resolution for local epidemiologic questions and sufficient reproducibility to enable international comparisons of clinical isolates. We defined a core genome multilocus sequence typing scheme comprising 2,038 loci and demonstrated its congruence with whole-genome single-nucleotide polymorphism variation. Most cases of intrafamilial groups of isolates or of multiple isolates recovered from the same patient were distinguished from temporally and geographically cocirculating isolates. However, epidemiologically unrelated isolates were sometimes nearly undistinguishable. We set up a publicly accessible core genome multilocus sequence typing database to enable global comparisons of B. pertussis isolates, opening the way for internationally coordinated surveillance.

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July 7, 2019  |  

BMScan: using whole genome similarity to rapidly and accurately identify bacterial meningitis causing species.

Bacterial meningitis is a life-threatening infection that remains a public health concern. Bacterial meningitis is commonly caused by the following species: Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Escherichia coli. Here, we describe BMScan (Bacterial Meningitis Scan), a whole-genome analysis tool for the species identification of bacterial meningitis-causing and closely-related pathogens, an essential step for case management and disease surveillance. BMScan relies on a reference collection that contains genomes for 17 focal species to scan against to identify a given species. We established this reference collection by supplementing publically available genomes from RefSeq with genomes from the isolate collections of the Centers for Disease Control Bacterial Meningitis Laboratory and the Minnesota Department of Health Public Health Laboratory, and then filtered them down to a representative set of genomes which capture the diversity for each species. Using this reference collection, we evaluated two genomic comparison algorithms, Mash and Average Nucleotide Identity, for their ability to accurately and rapidly identify our focal species.We found that the results of Mash were strongly correlated with the results of ANI for species identification, while providing a significant reduction in run-time. This drastic difference in run-time enabled the rapid scanning of large reference genome collections, which, when combined with species-specific threshold values, facilitated the development of BMScan. Using a validation set of 15,503 genomes of our species of interest, BMScan accurately identified 99.97% of the species within 16 min 47 s.Identification of the bacterial meningitis pathogenic species is a critical step for case confirmation and further strain characterization. BMScan employs species-specific thresholds for previously-validated, genome-wide similarity statistics compiled from a curated reference genome collection to rapidly and accurately identify the species of uncharacterized bacterial meningitis pathogens and closely related pathogens. BMScan will facilitate the transition in public health laboratories from traditional phenotypic detection methods to whole genome sequencing based methods for species identification.

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July 7, 2019  |  

Evolutionary emergence of drug resistance in Candida opportunistic pathogens.

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

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July 7, 2019  |  

Complete genome sequence of the multidrug-resistant neonatal meningitis Escherichia coli serotype O75:H5:K1 strain mcjchv-1 (NMEC-O75).

Neonatal meningitis Escherichia coli (NMEC) is the second leading cause of neonatal bacterial meningitis worldwide. We report the genome sequence of the multidrug-resistant NMEC serotype O75:H5:K1 strain mcjchv-1, which resulted in an infant’s death. The O75 serogroup is rare among NMEC isolates; therefore, this strain is considered an emergent pathogen.

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July 7, 2019  |  

Complete genome sequence of herpes simplex virus 2 strain 333.

Herpes simplex virus 2, or human herpesvirus 2, is a ubiquitous human pathogen that causes genital ulcerations and establishes latency in sacral root ganglia. We fully sequenced and manually curated the viral genome sequence of herpes simplex virus 2, strain 333 using Pacific Biosciences and Illumina sequencing technologies.

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July 7, 2019  |  

Complete genome sequences of historic Clostridioides difficile food-dwelling ribotype 078 strains in Canada identical to that of the historic human clinical strain M120 in the United Kingdom.

Clostridioides (Clostridium) difficile is a spore-forming anaerobic bacte- rium that causes severe intestinal diseases in humans. Here, we report the complete genome sequence of the first C. difficile foodborne type strain (PCR ribotype 078) isolated from food animals in Canada in 2004, which has 100% similarity to the ge- nome sequence of the historic human clinical strain M120.

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July 7, 2019  |  

Genomic features of the Helicobacter pylori strain PMSS1 and its virulence attributes as deduced from its in vivo colonisation patterns.

The human gastric pathogen Helicobacter pylori occurs in two basic variants, either exhibiting a functional cagPAI-encoded type-4-secretion-system (T4SS) or not. Only a few cagPAI-positive strains have been successfully adapted for long-term infection of mice, including the pre-mouse Sydney strain 1 (PMSS1). Here we confirm that PMSS1 induces gastric inflammation and neutrophil infiltration in mice, progressing to intestinal metaplasia. Complete genome analysis of PMSS1 revealed 1,423 coding sequences, encompassing the cagPAI gene cluster and, unusually, the location of the cytotoxin-associated gene A (cagA) approximately 15 kb downstream of the island. PMSS1 harbours three genetically exchangeable loci that are occupied by the hopQ coding sequences. HopQ represents a critical co-factor required for the translocation of CagA into the host cell and activation of NF-?B via the T4SS. Long-term colonisation of mice led to an impairment of cagPAI functionality. One of the bacterial clones re-isolated at four months post-infection revealed a mutation in the cagPAI gene cagW, resulting in a frame shift mutation, which prevented CagA translocation, possibly due to an impairment of T4SS function. Rescue of the mutant cagW re-established CagA translocation. Our data reveal intriguing insights into the adaptive abilities of PMSS1, suggesting functional modulation of the H. pylori cagPAI virulence attribute.© 2018 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

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July 7, 2019  |  

Complete genome sequences of three Leptospira mayottensis strains from tenrecs that are endemic in the Malagasy region

Leptospirosis is a zoonosis caused by Leptospira, a diversified genus containing more than 10 pathogenic species. Tenrecs are small terrestrial mammals endemic in the Malagasy region and are known to be reservoirs of the recently de- scribed species Leptospira mayottensis. We report the complete genome sequences of three L. mayottensis strains isolated from two tenrec species.

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July 7, 2019  |  

Genetic structure of four plasmids found in Acinetobacter baumannii isolate D36 belonging to lineage 2 of global clone 1.

Four plasmids ranging in size from 4.7 to 44.7 kb found in the extensively antibiotic resistant Acinetobacter baumannii isolate D36 that belongs to lineage 2 of global clone 1 were examined. D36 includes two cryptic plasmids and two carrying antibiotic resistance genes. The smallest plasmid pD36-1 (4.7 kb) carries no resistance genes but includes mobA and mobC mobilisation genes related to those found in pRAY* (pD36-2, 6,078 bp) that also carries the aadB gentamicin, kanamycin and tobramycin resistance gene cassette. These two plasmids do not encode a Rep protein. Plasmid pRAY* was found to be mobilised at high frequency by the large conjugative plasmid pA297-3 but a pRAY* derivative lacking the mobA and mobC genes was not. The two larger plasmids, pD36-3 and pD36-4, encode Rep_3 family proteins (Pfam1051). The cryptic plasmid pD36-3 (6.2 kb) has RepAci1 and pD36-4 (44.7 kb) encodes two novel Rep_3 family proteins suggesting a co-integrate. Plasmid pD36-4 includes the sul2 sulfonamide resistance gene, the aphA1a kanamycin/neomycin resistance gene in Tn4352::ISAba1 and a mer module in a hybrid Tn501/Tn1696 transposon conferring resistance to mercuric ions. New examples of dif modules flanked by pdif sites (XerC-XerD binding sites) that are part of many A. baumannii plasmids were also identified in pD36-3 and pD36-4 which carry three and two dif modules, respectively. Homologs of three dif modules, the sup sulphate permease module in pD36-3, and of the abkAB toxin-antitoxin module and the orf module in pD36-4, were found in different contexts in diverse Acinetobacter plasmids, consistent with module mobility. A novel insertion sequence named ISAba32 found next to the pdif site in the abkAB dif module is related to members of the ISAjo2 group which also are associated with the pdif sites of dif modules. Plasmids found in D36 were also found in some other members of GC1 lineage 2.

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July 7, 2019  |  

Genome analysis of Mycobacterium avium subspecies hominissuis strain 109.

Infection with Mycobacterium avium is a significant cause of morbidity and its treatment requires the use of multiple antibiotics for more than 12 months. In the current work, we provide the genome sequence, gene annotations, gene ontology annotations, and protein homology data for M. avium strain 109 (MAC109), which has been used extensively in preclinical studies. The de novo assembled genome consists of a circular chromosome of length 5,188,883?bp and two circular plasmids of sizes 147,100?bp and 16,516?bp. We have named the plasmids pMAC109a and pMAC109b, respectively. Based on its genome, we confirm that MAC109 should be classified as Mycobacterium avium subsp. hominissuis. Using genome annotation software, we identified 4,841 coding sequences and annotated these with Gene Ontology (GO) terms. Additionally, we wrote software to generate a database of homologous proteins among MAC109 and eight other commonly used mycobacterial laboratory strains. The resulting database may be useful for translating genetic data between various strains of mycobacteria, and the software may be applied readily to other organisms.

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July 7, 2019  |  

CTX-M-65 extended-spectrum ß-lactamase-producing Salmonella enterica serotype infantis, United States.

Extended-spectrum ß-lactamases (ESBLs) confer resistance to clinically important third-generation cephalosporins, which are often used to treat invasive salmonellosis. In the United States, ESBLs are rarely found in Salmonella. However, in 2014, the US Food and Drug Administration found blaCTX-M-65 ESBL-producing Salmonella enterica serotype Infantis in retail chicken meat. The isolate had a rare pulsed-field gel electrophoresis pattern. To clarify the sources and potential effects on human health, we examined isolates with this pattern obtained from human surveillance and associated metadata. Using broth microdilution for antimicrobial susceptibility testing and whole-genome sequencing, we characterized the isolates. Of 34 isolates, 29 carried the blaCTX-M-65 gene with <9 additional resistance genes on 1 plasmid. Of 19 patients with travel information available, 12 (63%) reported recent travel to South America. Genetically, isolates from travelers, nontravelers, and retail chicken meat were similar. Expanded surveillance is needed to determine domestic sources and potentially prevent spread of this ESBL-containing plasmid.

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July 7, 2019  |  

Emergence of tigecycline resistance in Escherichia coli co-producing MCR-1 and NDM-5 during tigecycline salvage treatment.

Here, we report a case of severe infection caused by Escherichia coli that harbored mcr-1, blaNDM-5, and acquired resistance to tigecycline during tigecycline salvage therapy.Antimicrobial susceptibility testing, Southern blot hybridization, and complete genome sequence of the strains were carried out. The genetic characteristics of the mcr-1 and blaNDM-5 plasmids were analyzed. The whole genome sequencing of mcr-1-containing plasmid was completed. Finally, putative single nucleotide polymorphisms and deletion mutations in the tigecycline-resistant strain were predicted.Three E. coli isolates were obtained from ascites, pleural effusion, and stool of a patient; they were resistant to almost all the tested antibiotics. The first two strains separated from ascites (E-FQ) and hydrothorax (E-XS) were susceptible to amikacin and tigecycline; however, the third strain from stool (E-DB) was resistant to tigecycline after nearly 3 weeks’ treatment with tigecycline. All three isolates possessed both mcr-1 and blaNDM-5. The blaNDM-5 gene was found on the IncX3 plasmid, whereas the mcr-1, fosA3 and blaCTX-M-14 were located on the IncHI2 plasmid. Mutations in acrB and lon were the reason for the resistance to tigecycline.This is the first report of a colistin-, carbapenem-, and tigecycline-resistant E. coli in China. Tigecycline resistance acquired during tigecycline therapy is of great concern for us because tigecycline is a drug of last resort to treat carbapenem-resistant Gram-negative bacterial infections. Furthermore, the transmission of such extensively drug-resistant isolates may pose a great threat to public health.

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