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Enterobacter bugandensis: a novel enterobacterial species associated with severe clinical infection.

ABSTRACT: Nosocomial pathogens can cause life-threatening infections in neonates and immunocompromised patients. E. bugandensis (EB-247) is a recently described species of Enterobacter, associated with neonatal sepsis. Here we demonstrate that the extended spectrum ß-lactam (ESBL) producing isolate EB-247 is highly virulent in both Galleria mellonella and mouse models of infection. Infection studies in a streptomycin-treated mouse model showed that EB-247 is as efficient as Salmonella Typhimurium in inducing systemic infection and release of proinflammatory cytokines. Sequencing and analysis of the complete genome and plasmid revealed that virulence properties are associated with the chromosome, while antibiotic-resistance genes are exclusively present on a 299?kb IncHI plasmid. EB-247 grew in high concentrations of human serum indicating septicemic potential. Using whole genome-based transcriptome analysis we found 7% of the genome was mobilized for growth in serum. Upregulated genes include those involved in the iron uptake and storage as well as metabolism. The lasso peptide microcin J25 (MccJ25), an inhibitor of iron-uptake and RNA polymerase activity, inhibited EB-247 growth. Our studies indicate that Enterobacter bugandensis is a highly pathogenic species of the genus Enterobacter. Further studies on the colonization and virulence potential of E. bugandensis and its association with septicemic infection is now warranted.

SUBMITTER: Pati NB

PROVIDER: S-EPMC5876403 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Enterobacter bugandensis: a novel enterobacterial species associated with severe clinical infection.

Pati Niladri Bhusan NB Doijad Swapnil Prakash SP Schultze Tilman T Mannala Gopala Krishna GK Yao Yancheng Y Jaiswal Sangeeta S Ryan Daniel D Suar Mrutyunjay M Gwozdzinski Konrad K Bunk Boyke B Mraheil Mobarak Abu MA Marahiel Mohamed A MA Hegemann Julian D JD Spröer Cathrin C Goesmann Alexander A Falgenhauer Linda L Hain Torsten T Imirzalioglu Can C Mshana Stephen E SE Overmann Jörg J Chakraborty Trinad T

Scientific reports 20180329 1

Nosocomial pathogens can cause life-threatening infections in neonates and immunocompromised patients. E. bugandensis (EB-247) is a recently described species of Enterobacter, associated with neonatal sepsis. Here we demonstrate that the extended spectrum ß-lactam (ESBL) producing isolate EB-247 is highly virulent in both Galleria mellonella and mouse models of infection. Infection studies in a streptomycin-treated mouse model showed that EB-247 is as efficient as Salmonella Typhimurium in induc ...[more]

PMID: 29599516

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Project description:BackgroundThe antimicrobial resistance (AMR) phenotypic properties, multiple drug resistance (MDR) gene profiles, and genes related to potential virulence and pathogenic properties of five Enterobacter bugandensis strains isolated from the International Space Station (ISS) were carried out and compared with genomes of three clinical strains. Whole genome sequences of ISS strains were characterized using the hybrid de novo assembly of Nanopore and Illumina reads. In addition to traditional microbial taxonomic approaches, multilocus sequence typing (MLST) analysis was performed to classify the phylogenetic lineage. Agar diffusion discs assay was performed to test antibiotics susceptibility. The draft genomes after assembly and scaffolding were annotated with the Rapid Annotations using Subsystems Technology and RNAmmer servers for downstream analysis.ResultsMolecular phylogeny and whole genome analysis of the ISS strains with all publicly available Enterobacter genomes revealed that ISS strains were E. bugandensis and similar to the type strain EB-247T and two clinical isolates (153_ECLO and MBRL 1077). Comparative genomic analyses of all eight E. bungandensis strains showed, a total of 4733 genes were associated with carbohydrate metabolism (635 genes), amino acid and derivatives (496 genes), protein metabolism (291 genes), cofactors, vitamins, prosthetic groups, pigments (275 genes), membrane transport (247 genes), and RNA metabolism (239 genes). In addition, 112 genes identified in the ISS strains were involved in virulence, disease, and defense. Genes associated with resistance to antibiotics and toxic compounds, including the MDR tripartite system were also identified in the ISS strains. A multiple antibiotic resistance (MAR) locus or MAR operon encoding MarA, MarB, MarC, and MarR, which regulate more than 60 genes, including upregulation of drug efflux systems that have been reported in Escherichia coli K12, was also observed in the ISS strains.ConclusionGiven the MDR results for these ISS Enterobacter genomes and increased chance of pathogenicity (PathogenFinder algorithm with > 79% probability), these species pose important health considerations for future missions. Thorough genomic characterization of the strains isolated from ISS can help to understand the pathogenic potential, and inform future missions, but analyzing them in in-vivo systems is required to discern the influence of microgravity on their pathogenicity.

Project description:Two Enterobacter strains 170198T and 170250T were isolated from clinical blood samples from distinct patients in a hospital in Chengdu, China, in 2022. These isolates were subjected to whole-genome sequencing. A phylogenomic tree based on 2,096 concatenated core genes showed that the two strains were clustered within the genus Enterobacter. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between each of the two strains and type strains of all currently known Enterobacter species were determined. The two strains belonged to two novel species as the highest ANI and isDDH values with type strains of all currently known Enterobacter species below the cutoff for species demarcation (96% for ANI and 70% for isDDH). Then the physiological and biochemical studies demonstrated that biochemical features and the profile of whole fatty acids of strains 170198T and 170250T were largely consistent with those known Enterobacter species. Nevertheless, the two novel species can be differentiated from all other Enterobacter species by certain biochemical characteristics. In conclusion, 170198T and 170250T represent two novel species of the genus Enterobacter, for which we propose Enterobacter chinensis sp. nov. and Enterobacter rongchengensis sp. nov., as the species names. The type strains of Enterobacter chinensis sp. nov., and Enterobacter rongchengensis sp. nov. are 170198T (=GDMCC 1.3549T=JCM 35826T) and 170250T (=GDMCC 1.3670T=JCM 36189T), respectively. The two novel species have clinical significance with the ability to cause bloodstream infections.IMPORTANCEEnterobacter is a group of bacteria comprising several common opportunistic pathogens and has a complicated taxonomy. Here, we reported two novel Enterobacter species. We demonstrated that the two novel species can be differentiated from other Enterobacter species by certain phenotypic characteristics and therefore provide information for designing tests for identification. We also showed that strains of the two novel species are able to cause human bloodstream infections and carry multiple virulence factors and therefore are of clinical significance. We highlight that the virulence of Enterobacter is less studied and warrants further exploration. We believe that the findings here are valuable for enhancing the appreciation toward Enterobacter, an important pathogen.

Project description:BackgroundEnterobacter bugandensis is an emerging human pathogen in which multidrug resistant strains have been continuously isolated from various environments. Thus, this organism possesses the potential to pose challenges in human healthcare. However, the mechanisms, especially the efflux pumps, responsible for the multidrug resistance in E. bugandensis remain to be well elucidated.MethodsThe Enterobacter strain CMCC(B) 45301 was specifically identified using whole genome sequencing. The specific CMCC(B) 45301 homologues of the TolC dependent efflux-pump genes characterized in Escherichia coli were identified. The tolC deletion mutant in CMCC(B) 45301 was constructed and subjected to susceptibility tests using 26 different antimicrobial agents, along with the wild type strain. The synergistic effects combining the Bacillus crude extract (BCE) and several other TolC-affected compounds against CMCC(B) 45301 were assayed.ResultsWe reclassified the Enterobacter CMCC(B) 45301 strain from species cloacae to bugandensis, on the basis of its whole genome sequence. We found that the CMCC(B) 45301 TolC, AcrAB, AcrD, AcrEF, MdtABC, EmrAB, and MacAB exhibit high similarity with their respective homologues in E. coli and Enterobacter cloacae. Our results for the susceptibility tests revealed that lacking tolC causes 4- to 256-fold decrease in the minimal inhibitory concentrations of piperacillin, gentamicin, kanamycin, tetracycline, norfloxacin, ciprofloxacin, chloramphenicol, and erythromycin against CMCC(B) 45301. In addition, the inhibition zones formed by cefuroxime, cefoperazone, amikacin, streptomycin, minocycline, doxycycline, levofloxacin, florfenicol, trimethoprim-sulfamethoxazole, azithromycin, lincomycin, and clindamycin for the tolC mutant were larger or more obvious than that for the parent. Our data suggested the important role played by TolC in CMCC(B) 45301 susceptibility to common antibiotic families covering ß-lactam, aminoglycoside, tetracycline, fluoroquinolone, phenicol, folate pathway antagonist, macrolide, and lincosamide. Deletion for tolC also increased the susceptibility of CMCC(B) 45301 to berberine hydrochloride and BCE, two natural product-based agents. Finally, we found that erythromycin, norfloxacin, and ciprofloxacin can potentiate the antibacterial activity of BCE against CMCC(B) 45301.DiscussionThe present study elaborated the comprehensive TolC effect on the antimicrobial susceptibility profile in E. bugandensis, which might contribute to the development of more therapeutic options against this nosocomial pathogen.

Project description:The genus Enterobacter comprises common pathogens and has a complicated taxonomy. Precise taxonomic assignation lays a foundation for microbiology. In this study, we updated the Enterobacter taxonomy based on robust genome analyses. We found that all Enterobacter subspecies assignments were incorrect. Enterobacter cloacae subsp. dissolvens and Enterobacter hormaechei subsp. hoffmannii are species (Enterobacter dissolvens and Enterobacter hoffmannii, respectively) rather than subspecies. Enterobacter xiangfangensis, Enterobacter hormaechei subsp. oharae, and Enterobacter hormaechei subsp. steigerwaltii are not Enterobacter hormaechei subspecies but belong to the same species (Enterobacter xiangfangensis). Enterobacter timonensis should be removed to Pseudenterobacter, a novel genus. We then reported two novel species, Enterobacter quasiroggenkampii and Enterobacter quasimori, by genome- and phenotype-based characterization. We also applied the updated taxonomy to curate 1,997 Enterobacter genomes in GenBank. Species identification was changed following our updated taxonomy for the majority of publicly available strains (1,542, 77.2%). The most common Enterobacter species was E. xiangfangensis We identified 14 novel tentative Enterobacter genomospecies. This study highlights that updated and curated taxonomic assignments are the premise of correct identification.IMPORTANCEEnterobacter species are major human pathogens. Precise species identification lays a foundation for microbiology, but the taxonomy of Enterobacter is complicated and confusing. In this study, first, we significantly updated the taxonomy of Enterobacter by rigorous genome analyses and found that all subspecies assignments of Enterobacter were incorrect. Second, we characterized and reported two novel Enterobacter species with clinical significance. Third, we curated 1,997 Enterobacter genome sequences deposited in GenBank and found that the species identification of most Enterobacter strains needed to be corrected. Fourth, we found that the most common Enterobacter species seen in clinical samples is Enterobacter xiangfangensis rather than Enterobacter cloacae Fifth, we identified 14 tentative novel Enterobacter and 18 tentative novel non-Enterobacter species. This study highlights that updated and curated taxonomic assignments are the premise of correct species identification. We recommend that future Enterobacter studies need to use the updated taxonomy to avoid misleading information.

Dataset Information

Enterobacter bugandensis: a novel enterobacterial species associated with severe clinical infection.

Publications

Enterobacter bugandensis: a novel enterobacterial species associated with severe clinical infection.

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