Deciphering the genetic basis of <i><scp>M</scp>oraxella catarrhalis</i> complement resistance: a critical role for the disulphide bond formation system

Vries, Stefan P. W. de; Rademakers, Rob J. A.; Jongh, Christa E. van der Gaast–de; Eleveld, Marc J.; Hermans, Peter W. M.; Bootsma, Hester J.

doi:10.1111/mmi.12475

Cited by 13 publications

(7 citation statements)

References 68 publications

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“…Furthermore, we detected a putative multidrug resistance (MDR) protein E (TcCLB.508965.14) highly upregulated in rdEpi ( p = 0.06); overexpression of a MDR P‐glycoprotein in a myeloid leukemia cell line confers resistance to complement‐mediated cytotoxicity (Weisburg et al ., ). Besides, recent studies showed that the disulfide bond formation system (Dsb) is critical for complement resistance in pathogenic bacteria (de Vries et al ., ; Ren et al ., ), suggesting that the development of Dsb inhibitors could have broad implications (Ren et al ., ). These may explain the up‐regulation of the T. cruzi ERO1 (eukaryotic endoplasmic reticulum oxidoreductin) only in rdEpi (Cluster 1), considered the eukaryotic equivalent of the Dsb system.…”

Section: Discussionmentioning

confidence: 99%

Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host

Kessler

Contreras

Marliére

et al. 2017

Molecular Microbiology

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Trypanosoma cruzi, the etiologic agent of Chagas disease, has a complex life cycle in which four distinct developmental forms alternate between the insect vector and the mammalian host. It is assumed that replicating epimastigotes present in the insect gut are not infective to mammalian host, a paradigm corroborated by the widely acknowledged fact that only this stage is susceptible to the complement system. In the present work, we establish a T. cruzi in vitro and in vivo epimastigogenesis model to analyze the biological aspects of recently differentiated epimastigotes (rdEpi). We show that both trypomastigote stages of T. cruzi (cell-derived and metacyclic) are able to transform into epimastigotes (processes termed primary and secondary epimastigogenesis, respectively) and that rdEpi have striking properties in comparison to long-term cultured epimastigotes: resistance to complement-mediated lysis and both in vitro (cell culture) and in vivo (mouse) infectivity. Proteomics analysis of all T. cruzi stages reveled a cluster of proteins that were up-regulated only in rdEpi (including ABC transporters and ERO1), suggesting a role for them in rdEpi virulence. The present work introduces a new experimental model for the study of host-parasite interactions, showing that rdEpi can be infective to the mammalian host.

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Section: Discussionmentioning

confidence: 99%

Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host

Kessler

Contreras

Marliére

et al. 2017

Molecular Microbiology

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“…coli (YchF) belongs to the GTPase family and is a negative regulator of the oxidative stress response 53 . YchF proteins have been implicated in pathogenesis of other bacterial species 53, 54 . With branched-chain amino acids (BCAA) being linked to chemotaxis 55 , livM , part of the ABC-type BCAA transport system ( livM , livH , livK , and livJ ), may be implicated in within host chemotaxis.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide fitness analyses of the foodborne pathogen Campylobacter jejuni in in vitro and in vivo models

Vries

Gupta

Baig

et al. 2017

Sci Rep

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Campylobacter is the most common cause of foodborne bacterial illness worldwide. Faecal contamination of meat, especially chicken, during processing represents a key route of transmission to humans. There is a lack of insight into the mechanisms driving C. jejuni growth and survival within hosts and the environment. Here, we report a detailed analysis of C. jejuni fitness across models reflecting stages in its life cycle. Transposon (Tn) gene-inactivation libraries were generated in three C. jejuni strains and the impact on fitness during chicken colonisation, survival in houseflies and under nutrient-rich and –poor conditions at 4 °C and infection of human gut epithelial cells was assessed by Tn-insertion site sequencing (Tn-seq). A total of 331 homologous gene clusters were essential for fitness during in vitro growth in three C. jejuni strains, revealing that a large part of its genome is dedicated to growth. We report novel C. jejuni factors essential throughout its life cycle. Importantly, we identified genes that fulfil important roles across multiple conditions. Our comprehensive screens showed which flagella elements are essential for growth and which are vital to the interaction with host organisms. Future efforts should focus on how to exploit this knowledge to effectively control infections caused by C. jejuni.

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“…Several molecular phylogenetic-typing methods, including restriction fragment length polymorphism analyses and multilocus sequence typing (MLST), have suggested that the M. catarrhalis species is composed of two main lineages ( Bootsma et al 2000a ; Pingault et al 2007 ; Wirth et al 2007 ), but that divergent strains with limited homology also exist ( Wirth et al 2007 ). The first described phylogenetic lineage, often referred to as the seroresistant (SR) lineage, contains 16S ribotype (RB) 1 strains and displays a more pathogenic profile as the vast majority of its members are complement resistant and adhere efficiently to respiratory epithelial cells ( de Vries et al 2013 , 2014 ). The other lineage, also known as the serosensitive (SS) lineage, consists of strains with RB2 and RB3, and mainly harbors M. catarrhalis isolates that are sensitive to complement-mediated killing and show less efficient adherence to respiratory epithelial cells ( Bootsma et al 2000a ; Pingault et al 2007 ; Wirth et al 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative Genomic Analyses of theMoraxella catarrhalisSerosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution

et al. 2016

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The bacterial species Moraxella catarrhalis has been hypothesized as being composed of two distinct lineages (referred to as the seroresistant [SR] and serosensitive [SS]) with separate evolutionary histories based on several molecular typing methods, whereas 16S ribotyping has suggested an additional split within the SS lineage. Previously, we characterized whole-genome sequences of 12 SR-lineage isolates, which revealed a relatively small supragenome when compared with other opportunistic nasopharyngeal pathogens, suggestive of a relatively short evolutionary history. Here, we performed whole-genome sequencing on 18 strains from both ribotypes of the SS lineage, an additional SR strain, as well as four previously identified highly divergent strains based on multilocus sequence typing analyses. All 35 strains were subjected to a battery of comparative genomic analyses which clearly show that there are three lineages—the SR, SS, and the divergent. The SR and SS lineages are closely related, but distinct from each other based on three different methods of comparison: Allelic differences observed among core genes; possession of lineage-specific sets of core and distributed genes; and by an alignment of concatenated core sequences irrespective of gene annotation. All these methods show that the SS lineage has much longer interstrain branches than the SR lineage indicating that this lineage has likely been evolving either longer or faster than the SR lineage. There is evidence of extensive horizontal gene transfer (HGT) within both of these lineages, and to a lesser degree between them. In particular, we identified very high rates of HGT between these two lineages for ß-lactamase genes. The four divergent strains are sui generis, being much more distantly related to both the SR and SS groups than these other two groups are to each other. Based on average nucleotide identities, gene content, GC content, and genome size, this group could be considered as a separate taxonomic group. The SR and SS lineages, although distinct, clearly form a single species based on multiple criteria including a large common core genome, average nucleotide identity values, GC content, and genome size. Although neither of these lineages arose from within the other based on phylogenetic analyses, the question of how and when these lineages split and then subsequently reunited in the human nasopharynx is explored.

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Deciphering the genetic basis of Moraxella catarrhalis complement resistance: a critical role for the disulphide bond formation system

Cited by 13 publications

References 68 publications

Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host

Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host

Genome-wide fitness analyses of the foodborne pathogen Campylobacter jejuni in in vitro and in vivo models

Comparative Genomic Analyses of theMoraxella catarrhalisSerosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution

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