A novel Integrative and Conjugative Element conferring Multidrug Resistance in Haemophilus influenzae
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PROVIDER: PRJEB52501 | ENA |
REPOSITORIES: ENA
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Project description:A multidrug-resistant (MDR) strain of Haemophilus influenzae, Hi-228, with phenotypic resistance toward ampicillin, cefotaxime, chloramphenicol, gentamicin, and azithromycin, was isolated in Oslo, Norway. The strain was part of a clonal outbreak (2016-2017) comprising five ST143 strains with identical resistotypes. Hi-228 carries a novel integrative and conjugative element (ICE), Tn7100, contributing to this remarkable and previously unreported MDR profile. Tn7100 contains the following resistance genes: bla TEM-1B, catA2, aac(6')-Im, aph(2″)-Ib, mef (E), and mel. The latter four are previously unreported or rarely reported in H. influenzae. In this study, we investigated the genetic environment, mechanisms of transfer, impact on phenotypic susceptibility, and fitness cost of this ICE. We found that Tn7100 has an overall structure similar to the previously described ICE Tn6686, with bla TEM-1B and catA2 carried by Tn3 and Tn10, respectively. The major difference between Tn7100 and Tn6686 is that Tn7100 lacks tet(B) but carries the resistance gene pairs aac(6')-Im and aph(2″)-Ib and mef (E) and mel. The gene pairs are located on the novel transposable elements Tn7470 and Tn7471, which have high sequence identities to a plasmid in Enterobacterales and an ICE in streptococcal species, respectively. Tn7100 does circularize and is transferable, however, at a low frequency. Head-to-head competition experiments showed that uptake of Tn7100 reduces bacterial fitness. Our study shows that MDR strains are capable of clonal spread and that the H. influenzae supragenome comprises an increasingly wide range of transferable resistance genes, with evidence of transfer from unrelated genera. The findings offer a glimpse into the genome dynamics of H. influenzae, highlighting the importance of rational antibiotic usage to contain antimicrobial resistance and the emergence of MDR strains in this important pathogen.
| S-EPMC9355037 | biostudies-literature
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. This SuperSeries is composed of the SubSeries listed below.
2009-01-21 | GSE11362 | GEO
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. Keywords: Transcription analyses
2009-01-21 | GSE11349 | GEO
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. Keywords: Transcription analyses
2009-01-21 | GSE11354 | GEO
Project description:H. influenzae R2866 contains a phase-variable DNA methylase modA10, by virtue of 16 tetrameric repeats present after the start codon. Gain or loss of repeats during replication by slipped-strand mispairing can result in a non-functional reading frame. Microarray analyses of wild-type and insertionally inactivated modA were performed to determine genes affected by phase variable modification.
2015-09-24 | GSE73349 | GEO
Project description:Haemophilus influenzae Genome sequencing
| PRJNA1072316 | ENA
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. This SuperSeries is composed of the following subset Series: GSE11349: Transcriptional profiling of FeHm effects on Haemophilus influenzae R2866 GSE11354: Transcriptional profiling of FeHm effects on Haemophilus influenzae 10810 Keywords: SuperSeries Refer to individual Series
2009-01-20 | E-GEOD-11362 | biostudies-arrayexpress